Advances in Veterinary Antimicrobial Therapy and Forensic Toxicology

134

RATIONAL MEANS OF ANTIMICROBIAL SELECTION IN VETERINARY PRACTICE

M.VIJAY KUMAR

The choice of antimicrobial agent in the clinical practice should be based upon susceptibility of the infecting organism to the drug concentrations achieved in the tissue and pharmacokinetic characteristics of the drug and its dosing protocol. Although, several class of antimicrobials are readily available, the clinical cure may not be always successful and its partially attributable to lack of culture and sensitivity tests under field conditions. Therefore, atleast, one can bank upon certain pharmacokinetic principles in the routine clinical practice as well as in serious infections like meningitis, endocarditis and in immuno-compromised hosts.

Pharmacokinetics:

Pharmacokinetics deals with absorption, distribution, metabolism and excretory pattern of a given therapeutic agent. Selection of antimicrobial agent based on its pharmacokinetic characteristics aid in achieving optimal concentration at the desired site. For example, the location of infection can have a major influence on the drug concentration achieved there, as some sites (eg: CNS) are protected by barriers to drug penetration, while others (eg. mammary gland, urinary tract) local pH may favour drug accumulation. Knowledge of pharmacokinetic data is also useful to avoid possible toxicity in a given species as well to take necessary precautions during physiological stress (eg. pregnancy, lactation) or pathological conditions (eg: hepatic failure, renal dysfunction). The probable antimicrobial agent that can be employed in the clinical practice should be selected after giving due considerations to following issues:

organ/s is/are involved Most likely pathogen Antibiotic likely to be effective Drug concentrations at the site of infection Drug/route likely to achieve that concentration

Absorption: The absorption and disposition of antimicrobial agents in the body arelargely governed by their chemistry and certain physiochemical properties as well as status of the animal (Fig.1). The various antimicrobials are basically grouped into weak

KVC Sponsored CVE training programme on “Advances in Chemotherapy and Forensic Toxicology” organized by the Dept.of Pharmacology &Toxicology,Veterinary College,Bidar,from 31st January to 5th February, 2011

134

organic electrolytes (acids/bases), amphoteric or neutral compounds. The absorption is primarily dependent on extent of lipid solubility and degree of ionization,

which are determined by pKa of the drug and pH of the biological fluid in question. These factors also determine the extent of distribution and elimination process for antimicrobials. Only non-ionized forms of drugs are passively diffuses across GIT or can pass across blood-brain or blood-milk barrier. For acidic drugs, a fall in 1 pH unit results in a 10 fold increase in the concentration of the non-ionized form and converse applies for organic bases.

Distribution and elimination: Some of the lipophilic antimicrobials listed below enter most tissues of the body and penetrate cellular barriers and can generally reach infection foci. Chloramphenicol,Trimethoprim,Erythromycin,Metronidazole,3rd generation cephalosporins like moxalactam,Fluoroquinolones:Enrofloxacin, Pefloxacin, Ofloxacin, Norfloxacin.These antimicrobials are eliminated mainly by hepatic metabolism and/or carrier mediated biliary exertion. This rate of elimination varies with species, but obeys first order kinetics when therapeutic doses are administered.

Tetracyclins: The lipid solubility of tetracyclins varies with the compound but enter most tissues and body fluids except CSF. The more lipophilic number, minocycline attain effective concentration at relatively inaccessible infection site, such as the prostate. As a result of chelation with calcium, tetracyclins become bound at active sites of ossification and in developing teeth. Long acting tetracyclins (doxycyline, minocycline) undergo biliary excretion and may adversely affect indigenous microbes in the caecum/colon of horses. However, they are suited for biliary and upper intestinal tract infection in farm animals. Oxytretracyclin in 2-PVP base (IM only) exert long duration of action over propylene glycol base. Because of poor water solubility, oxytetracyclin dihydrade must be given in much higher dose (50 mg/kg) than the hydrochloride salt to produce equivalent tissue concentration.

Sulfonamides: Most of the sulfonamides predominantly non-ionized in biological fluid of pH below their pKa value (sulfisoxzole = 5; sulfonilamide = 10.4). Commonly used compounds like sulfamethazine (pka = 7.4) and sulfadimethoxin (pKa = 6.1) enter most tissues of the body and eliminated by a combination of metabolic reactions (acetylation) and renal exertion (filteration and pH - dependent passive tubular reabsorption). Cats are poor acetylators and therefore sulfonamides are contraindicated. Sulfisoxazole (pKa = 5.0) is more ionized in the plasma and widely distributed and eliminated mainly by glomerular filtration (best suited for UTI), but their exerction is dependent on urinary pH.

Penicillins: Distributions of penicillin are limited due to high ionization and they attain low concentration in cells and do not penetrate well into transcellular fluids. Protein binding varies


134

among penicillin over a wide range (80%-cloxacillin, 22%-ampicillin) and this is responsible for low extra-vascular distribution. However, penicillin and/or in combination with streptomycin is best suited for lower respiratory tract infection (unknown pathogen) with exudation. Penicillins are rapidly eliminated by kidney. Probencid compete with their excretion (for tubular excretion) and delays penicillins excretion.

Antibiotic Desired environment for optimal action

Penicillins,Hexamine(only UTI)

Nitrofurazones,Cephalosporins

Acidic pH

Tetracyclins,Fluoroquinalones,Aminoglycosides

Alkaline pH

Ampicillin, amoxicillin and naficillin undergoes enterohepatic circulation and therefore their half-lives are longer than penicillin-G. Penicillins and cephalosporins (beta-lactams) are highly active during logarithmic phase of bacterial growth (time dependent action). Dosing of beta-lactams should be aimed to keep serum concentration over MIC to prevent regrowth. Penicillins retains their activity even in the presence of fibrin and abscess formation.

Antibiotic Factors decrease their action

Sulfonamides Pus, blood clot

Penicillin,Cephalosporins,Aminoglycosides Intracellular organisms

Gentamicin,Polymyxin Pus

Aminoglycosides DecreasedpH,anaerobiasis, hyperosmalarity

Aminoglycosides :

Aminoglycosides does not attain therapeutic levels in CSF and ocular fluid. Poor diffusibility is attributed to this low degree of lipid solubility. Hafl-lives are short (1-2 hr) in domestic animals. Inspite of limited distribution, selective binding to renal tissue (cortex) occurs. Their bacteriocidal action is rapid but killing of Gm-ve aerobes is concentration dependent and produce a prolonged post-antibiotic effect. Due to this biphasic mode of action, serum concentration continuously exceeding MIC are not required unlike penicillins. Loop diuretics and impaired renal function delays their renal excretion and it is necessary to adjust maintenance dosage to prevent ototoxicity and nephrotoxicity. One should not administer large IV dose or multiple injections in dehydration or ureamic conditions. Intravenous eg: neomycin) must be restricted to one or two occasions only. Systemic administration does not give satisfactory levels in milk and therefore local (intramammary) route should be employed in mastitis cows.


134

Chloramphenicol: In pre-ruminant calves, chloromphenicol is well absorbed from GIT following systemic administration. The drug readily pass through cellular barriers and attain sustained concentration in CSF and aqueous humor. The drug can readily cross placenta. Penetration of the blood: prostate barrier is relatively poor. Due to lipophilic nature, the apparent volume of distribution is large (> 1L/kg) in all species and its distribution is independent of pH. It possess short half-lives in most species except cat (poor in conjugation with glucoronic acid). Due to short of half-life chloromphenicol (sodium succinate) at the rate of 50 mg/kg (priming dose) followed by maintenance doses of 25 mg/kg at 8-12 interval is suggested in ruminants.

Fluoroquinolones:

These are amphoteric compounds and having low degree of ionization. Therefore, their distribution is widespread and even penetrate well into CSF (>50% serum levels in meningitis), bronchial secretions, bone and cartilage and prostatic tissue. Partially metabolised in liver and bile concentrations are 2-10 times the serum levels and even enterohepatic circulation may occur. Plasma half-lives varies with species and urinary concentration exceed serum concentration by several hundred times and remain high for 24 hr after administration. Clearance of certain drugs like theophylline get reduced leading to adverse effects and one should not administer concurrently. They have affinity for weight bearing cartilages and therefore do not administer to puppies (before 8 months of age) or foals (below 1 year of age). Reduction of dosage is required in animals with impaired renal function.

Antimicrobial combinations and their effect

Bacteriostatic (systemic) + bacteriocidal (systemic) Antagonistic

Bacteriostatic (local) + bacteriocidal (systemic) Antagonistic

Bacteriocidal (local) + bacteriostatic (systemic) Antagonistic

Chloramphenicol + Aminoglycosides Antagonistic

Macrolid + Chloramphenicol Antagonistic

Conclusion:

The antimicrobial chemotherapy particularly in the absence of antibiotic sensitivity testing facility under field conditions is a difficult task. In the routine clinical practice as well as in the absence of microbial sensitivity pattern, one can adopt certain pharmacological principles discussed here so as to obtain clinical and/or bacterological


134

cure. The veterinarian must update their knowledge pertaing toclinical pharmacology of newer antimicrobials released in to market.

*****


134

AN UPDATE IN VETERINARY BIOLOGICALS

Y.HARI BABU

Vaccine is preparation of processed, innocuous specific antigen sometimes together with adjuvants. This preparation when introduced in to animal system (preferably) parenterally induces production of specific proteins called antibodies (Immunoglobins).

Presence of these antibodies in the circulating blood system confers high degree of immunity in the host body, against pathogens in the events of real infection. Obviously the antigens mentioned above are proteins derived from pathogens or disease causing organism. These proteins neutralize the pathogens invitro and prevent their growth.

Vaccination is something like Army exercise, mock war, war games to keep the body in readiness to take on any infection. The body has a wonderful mechanism of Anamnesis (remembering) and would switch on production of specific antibodies in short time.

The antigens are of great help in:

Inducing immunity in host. Providing diagnostic reagent for detecting the disease. Since the days of Jenner, a

vaccine has become life saving preparation and constitutes the main weapon against infections and contagious diseases. Vaccines are available against almost all infectious agents.

Types of vaccine:

Obviously the vaccines and vaccinations have brief history. The early vaccine were prepared out of material contents from wounds, lesions etc., of the affected individual. The material thus collected would be processed to remove accessory adhesions and impurities. The material would be rendered innocuous enough to be safe for .Then it used to be administered in prescribed doses.

Now the vaccines are produced on large scale, freezes dried and are preserved safely- ready for use in moments notice. Instead of whole organisms being included in vaccine preparation, only specific proteins responsible for ‘Antigenicity’ are being included in the vaccines. This procedure reduces all sorts of risks posed by the presence


134

of extraneous materials. Today most of the diseases are controlled. For this credit goes to vaccines, which were evolved over a period of time. Best example of vaccine utility is the elimination of pox from globe. Recent success of total containment or RinderPest in A.P. and Karnataka only reflect the glory of these vaccines. We have following kinds of vaccines today in market.

Killed vaccines Live vaccines Attenuated vaccines vector vaccines Subunit vaccines Very soon we will have transgenic vaccines. Other classification is: Bacterial vaccines Viral vaccines Protozoan vaccines Antitoxin Anti venom (snake etc.)

Vaccine failure in animals and birds:

Failures in vaccination are a common phenomenon which is being encountered by the veterinarian in the field, either in case of animals or birds. It is more so in poultry which, has become a challenge to both the field Veterinarian a well as to the biological manufacturers. To arrive at a proper conclusion about where actually the vaccinations have failed and how to correct it, one has to know, various ways in which a vaccine may fail to protect an animal and birds.

There are many reasons why a vaccine may not confer protective immunity on an animal. These can be discussed in brief hereunder.

Animal and Birds

1. Immunosuppressed2. Passive immunization 3. Parasitic immunization4. Biological variation

Vaccine:


134

1. Death of live vaccine2. Defect in storage vaccine3. Cold chain failure for live vaccines.

Vaccination:

1. Inappropriate route of administration2. Administration of passively protected animal/bird3. Inadequate vaccine4. Vaccine given too late to animal/bird already infected5. Wrong strain or organism used6. Non-protective antigen used.

Now we will discuss about the aforesaid factors in brief

ANIMAL /BIRDS

Animal or birds which are immunosuppressed:

This type of vaccine failure is very common in poultry, occurs when the normal immune response is suppressed. For example, malnourished animals may be immunosuppressed and should not be vaccinated. Some viral infections like infectious bursal disease (IBD or Gumboro disease) induce profound immunosupression.

Stress in general including pregnancy, extremes of cold, heat, fatigue, may reduce a normal immune response. Probably because of increased steroid production.

Passive immunization:

The most important cause of vaccine failure is the presence of passively derived maternal immunity in young animals.

In case of chick; serum immunoglobulin are readily transferred from hen serum to yolk while the egg is still in the ovary. In this fluid phase of yolk, IgG is therefore found at level equal to those in hen serum. In addition, as the egg passes down the oviduct, IgM and IgA from oviduct secretions are acquired with the albumin. As the chick embryo develops, it absorbs some of the yolk IgG which then appears in its circulation. The maternal IgM and IgA from the albumin diffuse in to the amniotic fluid and are swallowed by the embryo, so that when the chick hatches. It posses IgG in its serum and IgM and IgA in its intestine. The newly hatched chick doses not absorb all its yolk sac antibody until about 24 hrs after hatching. These maternal antibodies effectively prevent successful vaccination until they disappear between 10 and 20 days after hatching.


134

In case of animals, the maternal antibodies reach the fetus through the placenta, and it is determined by the structure of placenta. The placenta of ruminants as syndesmochorial; that is, the chorionic epithelium is in direct contact with uterine tissue. In animal with these types of placenta, the transplacental passage of Ig is prevented and the newborn of these species are thus entirely dependent on the antibodies secured through the colostrums.

Parasitic infestation:

Immune response is also suppressed in heavily parasitized animals or birds. Thats why, to induce proper immune response in birds against vaccination, it was suggested to deworm the bird against antihelmintics prior to vaccinations.

Biological variation:

The immune response, being a biological process never confers absolute protection and is never equal in all members of genetic and environmental factors, the range of immune responses in large random population of animal tends to follow a normal distribution. This means that most animals respond to antigen by mounting an average immune response, a few will mount an excellent response and a small proportion will mount a very poor immune response. The group of poor responders may not be protected against infections in spite of having received an effective vaccine. Therefore, it is impossible to guarantee 100% protection in random population of animals by vaccination.

VACCINE

Sometimes, the quantity of vaccine, handling of vaccine also affect the failure of immune-response against vaccination.

Death of live vaccine:

In some cases, the vaccine may actually be ineffective. This could be because it contains the wrong strain of organism or wrong antigens. The method of production may have destroyed the protective epitopes, or there may simply be insufficient antigen in the vaccine, of much greater importance is the failure of an effective vaccine to stimulate protective immunity. A live vaccine may have died as a result of poor storage, the use of antibiotics in conjunction with live bacterial vaccines, the use of chemicals to sterilize syringes or excessive use of alcohol while swabbing the skin.

Death in storage of vaccine:


134

The storage of vaccine is important in order to maintain the quality of vaccine. It holds good both for bacterial as well as viral vaccines even though it needs exacting low temperatures to store the vaccines. It is a common phenomenon in the field especially the storage of vaccines is concerned.

Cold chain failure for the live vaccines:

There are many live vaccines needed to be vaccinated to either birds or animals. Transport of such vaccines from the point of production to the institute or hospital and then to the point of vaccination needs the cold chain, as most of the live vaccines get destroyed in absence of cold atmosphere. This is one of the most important aspects to be observed and followed strictly in field to ascertain effective results out of vaccinations.

Vaccine Production defect:

It is not uncommon, that there arise doubts about the quality of vaccine many times in the minds of the field veterinarian. It is true and problems of this type are uncommon and can generally be avoided by using only vaccines from reputable manufacturers.

VACCINATIONS

Finally much of the task of making successful vaccination programme lies with the Veterinarian or Para veterinarian who is administering the vaccines. As the aforesaid aspect is limited involvement of the expertise of the Veterinarian, the methodology of vaccination, choosing of the vaccine, time of vaccination etc., which are discussed hereunder falls within intelligentsia of field worker or veterinarian.

Inappropriate route of administration:

Inappropriate route of administration is of much greater significance in the failure of an effective vaccine to stimulate protective immunity. In many cases, this is due to unsatisfactory administration. Inappropriate route of administration if vaccines to animals or birds lead to vaccination failure.

Administration of passively protected animal/bird:

As it has been discussed earlier, that the maternal antibodies that are present in the animals or birds will hamper the vaccination processes, by effectively neutralizing the vaccine antigens and making the vaccination ineffective. And hence, here it is stressed that before the vaccination, it has to be ascertained whether the maternal antibodies are


134

still present or not .For this, simple laboratory techniques are available or even history of the animal also reveals the required information.

In-adequate vaccine:

Sometimes, animals/birds given vaccines by unconventional routes may not be protected. When large flock of poultry as to be vaccinated, it is common to administer the vaccine eighter as an aerosol or in drinking water. If the aerosol is not evenly distributed throughout a building or if some animals do not drink may receive insufficient vaccine. Animal/birds that subsequently develop disease may be interpreted as cases of vaccine failure.

Vaccine given too late to animal/bird already infected:

Even animal given an adequate dose of an effective vaccine may fail to be protected. If the vaccinated animal was incubating the disease before inoculation, the vaccine may be given too late to affect the course of the disease. In such cases, more commonly, the animal/birds may fail to mount an immune response.

Wrong strain or organism used and Non-protective antigens used

The size of unreactive portion of the population will vary between vaccines, and its significance will depend on the nature of the disease. This for highly infectious diseases against which herd immunity is poor and in which infection is rapidly and effectively transmitted, such as foot and mouth disease, the presence of unprotected animals could permit the spread of the disease and would thus disrupt control programmes.

*****


134

AN UPDATE IN DISEASE INVESTIGATION AND DIAGNOSIS

K.C. Mallinath

INTRODUCTION:

In recent years disease diagnosis and disease management have become a highly specialized science. There was a time when people used to focus attention on a fewer diseases of livestock. Now, the scene is different, importation of highly productive germplasm, intensive cross breeding, extensive and intensive rearing of livestock, composite farming, extensive use of biologicals either imported or unwittingly smuggled from unknown sources have totally changed the disease scenario. Each species of domestic livestock now have a long list of diseases to be handled, some of them go unrecognized; a few have identical symptoms, some with confusing clinical signs.

Normally a field officer recognizes a disease based on classical clinical signs and deals with such a disease at his level. In the changed scenario as mentioned above where the clinical signs are confusing he has to depend on the referral diagnostic laboratory.

This confirmation process surely depends on the clinical samples made available to the laboratory. Therefore, the clinical material becomes a very valuable raw material for the success of the mission of disease diagnosis. Proper collection of relevant material and dispatching it to the laboratory in proper condition should be done with utmost care. Any negligence in this exercise may lead to faulty diagnosis leading to loss of valuable life of vulnerable livestock population and loss of precious time in dealing with field outbreaks.

A. COLLECTION OF SAMPLESBefore collection of samples, careful consideration should be given to the purpose for

which they are required. This will determine the type and number of samples needed to provide valid results. The samples should be collected aseptically, and care should be taken to avoid cross contamination between samples. When samples are taken from live animals, care should be taken to avoid injury or distress to the animal or danger to the operator and attendants. It may be necessary to use mechanical restraint, tranquilization or anesthesia. Whenever handling biological material, from either live or dead animals, the risk of zoonotic disease should be kept in mind and precautions taken to avoid human infection.


134

Post-mortem examinations should be carried out under as aseptic conditions as is practicable. Care should be taken to avoid environmental contamination or risk of spread of disease through insects or fomites. Arrangements should be made for appropriate safe disposal of animals and tissues. The samples collected should be representative of the condition being investigated and the lesions observed. Frequently, a combination of blood samples for serology and tissues from dead or culled animals for microbiological culture and pathological examination will be required.

For diagnostic purposes various types of specimens may be collected from live, dead animals and environment.1. Sample collection from live animals: a) Blood:

Blood samples may be taken for hematology or for culture and / or direct examination for bacteria, viruses or protozoa, in which case it is usual to use anticoagulants, such as ethylene diamine tetra-acetic acid (EDTA) or heparin. They may also be taken for serology, which requires a clotted sample. Blood plasma is also used for some procedures.

A blood sample is taken, as cleanly as possible, by venipuncture. In most large mammals, the jugular vein or a caudal vein is selected, but brachial veins and mammary veins are also used. Vena cava veins are also used in pigs. In birds, a wing vein (brachial vein) is usually selected. Blood may be taken by syringe and needle or by needle and vacuum tube (not easy in delicate veins but convenient in strong veins).Ideally the skin at the site of venipuncture should first be shaved (plucked) and swabbed with 70% alcohol and allowed to dry.

For samples that are collected with anticoagulant, thorough mixing, using gentle agitation only, is necessary as soon as the sample has been taken. It may also be necessary to make a smear of fresh blood on a microscope slide; both thick and thin. For polymerase chain reactions, EDTA is the preferred anticoagulant. For serum samples, the blood should be left to stand at ambient temperature (protected from excessive heat or cold) for 1–2 hours until the clot begins to contract. The clot can then be ringed round with a sterile rod and the bottles placed in a refrigerator at 4°C. After several hours, or overnight, the sample can be centrifuged at about 1000 g for 10–15 minutes and the serum can be decanted or removed with a pipette.Chemical preservatives viz., Thiomersal or Merthiolate or Sodium Azide can be used for longer storage of serum sample. In order to establish the significance of antibody titres, paired serum samples willoften need to be collected 7–14 days apart. b) Faeces:


134

Freshly voided faeces of suitable quantity (at least 10 g) should be collected. Faeces for parasitology should fill the container or topped up with sterile water and be sent to arrive at the laboratory within 24 hours. If transport times are likely to be longer than 24 hours, the sample should be sent on ice or refrigerated to prevent the hatching of parasite eggs.

Screw top containers or sterile plastic bags should be used for shipment; avoid tubes with rubber stoppers as gas generated can result in blowing the stopper off the tube, ruining the integrity of the sample and contaminating other samples in the package. An alternative and sometimes preferable method is to take swabs from the rectum (or cloaca), taking care to swab the mucosal surface. However, samples collected with a swab are inadequate for parasitology. Swabs should be transported in appropriate transport medium. Faeces are best stored and transported at 4°C.c) Skin:

In diseases producing vesicular lesions, collect, if possible, 2 gm of affected epithelial tissue as aseptically as possible and place it in 5 ml phosphate buffered glycerin or Tris-buffered tryptose broth virus transport medium at pH 7.6. Plucked hair or wool samples are useful for surface-feeding mites, lice and fungal infections. Deep skin scrapings, using the edge of a scalpel blade, are useful for burrowing mites. d) Genital tract and semen:

Samples may be taken by vaginal or prepucial washing or by the use of suitable swabs. The cervix or urethra may be sampled by swabbing. Samples of semen are best obtained using an artificial vagina or by extrusion of the penis and artificial stimulation. The sperm-rich fraction should be present in the sample and contamination by antiseptic washing solutions should be avoided. Specific transport media and conditions are often required.e) Eye:

A sample from the conjunctiva can be taken by holding the palpebra apart and the swab is then taken into the transport medium. Scrapings may also be taken on to a microscope slide. Thehandles of metal-handled swabs are useful for this, to ensure that sufficient cells are removed formicroscopic examination. f) Nasal discharge:

Samples may be taken with dacron, cotton or gauze swabs, preferably on wire handles as wood is inflexible and may snap. It may be helpful if the swab is first moistened with transport medium. The swab should be allowed to remain in contact with the secretions for up to 1 minute, then placed in transport medium and sent to the laboratory without delay at 4°C.


134

g) Milk:Milk samples should be taken after cleansing and drying the tip of the teat and the

use of antiseptics should be avoided. The initial stream of milk should be discarded and a tube filled with the next stream(s), a sample of bulk tank milk can be used for some tests. Milk for serological tests should not have been frozen, heated or subjected to violent shaking. If there is going to be a delay in submitting them to the laboratory, preservatives can be added to milk samples that are being collected for serological testing. h) Urine:

Urine samples should be collected with the help of a sterile catheter and dispatched in screw cap tube. Boric acid may be added as a preservative2. Sample collection at post-mortem:

Samples of tissue from a variety of organs can be taken at post-mortem. It is unusual to take biopsy samples of tissues in veterinary practice however are done in certain circumstances, using appropriate surgical techniques.

Animal health personnel should be trained in the correct procedures for post-mortem examination of the species of animals with which they work. The equipment required will depend on the size and species of animal. Normally a knife saw cleaver, scalpel, forceps and scissors, including scissors with a rounded tip on one blade will be required. A plentiful supply of containers and tubes of transport media appropriate to the nature of the sample required should be available, along with labels and report forms. Containers should be fully labeled with the date, tissue and animal identification. Special media may be required for transport of samples from the field. The operator should wear protective clothing,overalls, washable apron, rubber gloves and rubber boots. Additionally, if potential zoonotic diseases are being investigated, the post-mortem examination should be conducted in a biological safety cabinet; if this is not possible, an efficient face mask and eye protection should be worn. If rabies or transmissible spongiform encephalopathies (TSEs) are suspected, it is usual to detach the animal’s head.

Tissues may be collected for microbiological culture, parasitology, biochemistry, histopathology and/or immunohistochemistry, and for detection of proteins or genome nucleic acids. In addition buccal, oropharyngeal or rectal (cloacal) swabs may be collected. The person conducting the post-mortem examination should have sufficient knowledge of anatomy and pathology to select the most promising organs and lesions for sampling. Each piece of tissue should be placed in a fully labeled separate plastic bag or sterile screw-capped jar. Swabs should always be submitted in appropriate transport media. Disinfectants should not be used on or near tissues to be sampled for bacterial culture or virus isolation.


134

After collection, the samples for microbiological examination should be refrigerated until shipped. If shipment cannot be made within 48 hours, the samples should be frozen; however, prolonged storage at –20°C may be detrimental to virus isolation. For histopathology, blocks of tissue not more than 0.5 cm thick and 1–2 cm long are cut and placed in neutral buffered 4–10% formalin, which should be at least ten times the volume of the tissue sample. The tissues may be sent to the laboratory dry or in bacterial or virus transport medium, depending on the type ofspecimen and the examinations required.


134

3. Environmental and feed sampling:Samples may be taken to monitor hygiene or as part of a disease enquiry.

Environmental samples are commonly taken from litter or bedding and voided faeces or urine. Swabs may be taken from the surface of ventilation ducts, feed troughs and drains. This kind of sampling is particularly important in hatcheries, artificial insemination centres and slaughter houses in which specialized equipment is maintained. Samples may also be taken from animal feed, in troughs or bulk containers. Water may be sampled in troughs, drinkers, header tanks or from the natural or artificial supply.

B. SELECTION OF SAMPLEConsiderable skill and care are required to decide on the correct samples to be sent

to the laboratory. The experimental or field condition will suggest in good part about the appropriate sample and method of collection for microbiological study. However there are number of factors which will determine the effectiveness of sample collection. Among these are 1) Time of collection 2) Tissue selected 3) Handling and storage of the samples.

It is best to obtain sample from an animal as early as possible in the course of the disease. Avoid waiting to take sample until an animal moribund and near to death. The site of multiplication may be so destroyed as to no longer yield the viable organisms. Wherever possible specimen should be collected over a period of time. The specimens collected should be representative of the condition/population/organ. Proper quantity of sample collected as per the need.

C. INFORMATION TO BE SENT WITH SAMPLESIt is essential that individual samples be clearly identified using appropriate

methods. Marking instruments should be able to withstand the condition of use, i.e. being wet or frozen (use indelible marking pen). Pencil has a tendency to rub off containers and labels attached to plastic will fall off when stored at –70°C. Information and case history should always accompany the samples to the laboratory, and should be placed in a plastic envelope on the outside of the shipping container. The information should include the following points.i) Name and address of owner with telephone and fax numbers.ii) Diseases suspected and tests requested.iii) The species, breed, sex, age and identity of the animals sampled.iv) Date samples were collected and submitted.v) List of samples submitted with transport media used.vi) A complete case history would be beneficial for the laboratory and should be included if possible. Some of the components of the history are: a) A list and description of the animals examined. b) The length of time sick animals have been on the farm; if they are recent arrivals, from


134

where did they originate. c) The date of the first cases and of subsequent cases d) A description of the spread of infection in the herd or flock. e) The number of animals on the farm, the number of animals dead, the number showing clinical signs,and their age, sex and breed. f) The clinical signs exhibited by the affected animals and manage mental practices followed in the farm g) Any medication given to the animals, and when given. h) Any vaccines given, and when given. i) Post mortem lesions recorded.

D.TRANSPORTATION OF SAMPLES1. Approval to ship specimens:

The laboratory that is going to receive the samples should be contacted to ensure that it has the capability to do the testing requested and to see if there are any special packaging or shipping requirements. It is essential to contact the receiving laboratory when material is sent to another country. A special import license will usually be required for shipment of any biological material to other countries and must be obtained in advance. This license should be placed in an envelope on the outside of the parcel.

Shipments must be made in accordance with the Dangerous Goods Rules (DGR) for the particular mode of transport. For air transport it is the International Civil Aviation Organization (ICAO) technical instructions for the safe transport of dangerous goods by air. 2. Transportation of specimens:

Samples referred to as diagnostic specimens in official regulations must carefully be packed to avoid any possibility of leakage or cross contamination.

The specimens should be forwarded to the laboratory by the fastest method available. If they can reach the laboratory within 48 hours, samples should be sent refrigerated. E. PRESERVATION OF SAMPLES FOR PROLONGED STORAGE

Establishing a collection of samples for future studies can be very useful. This can include cultures for comparison with future isolates, tissue or serum samples that can be used for the validation of new tests and a collection of fixed tissues, or paraffin blocks, for future histological examination. Possibly the most useful collection is the storage of serum samples. These samples may be useful if a retrospective investigation is carried out to compare the present disease status with that of earlier times. The different methods of preserving the clinical samples are:


134

1) Short term storage (upto 24 hrs) at refrigeration2) Long term storage: a) Freezing the sample at -20o C/-60o C/-80o C/ -196 (LN2) can preserve up to 1 year without any alteration in the clinical material. b) Lyophilisation (Freeze drying) The water content of clinical material (specially viral origin) is removed and kept in powder form. This is the common method used for vaccines stored at 40 C.The nature of samples recommended for Bacterial, Viral, Fungal, Parasitic & other diseases are as follows: Name of the Disease Samples to be collected

Bacterial and Fungal Diseases

Hemorrhagic Septicemia : Fixed smears of blood/throat swelling in ailing animals Smears of heart blood & liver, heart blood, lymph node & spleen in dead animals

Anthrax : Flame fixed blood smears of cattle & sheep, swabs of blood from ear vein for cultural examination from dead animals or small piece from tip of ear/muzzle in saline

Black Quarter : Impression smears from the affected muscle tissue or exudates

Enterotoxemia / Contents of small intestine with and without chloroform separately on ice, Kidney, Urine

Brucellosis : Paired serum sample, blood and abomasal contents of aborted foetus, placenta with 2-3 cotyledons/vagina swabs in PBS

Johne’s disease Rectal pinch smears, Bowl washings preserved in 10% formalin & in dead animals terminal portion of ileum with ileocaecal valve, mesenteric lymph node in 10% formal saline

Glanders : Exudate from skin & lung lesions / its smears Tuberculosis : Cough material in sterile tube in live animal or milk sample in

sterile tube /smears from suspected lesions and lymph glands or lung lesions in sterile tube & in 50% buffered glycerin.

Leptospirosis : Blood serum, Pieces of liver in 10% formalin or milk or urine in vials adding 1 drop of formalin/ 20 ml

Salmonellosis : Intestinal swab, heart, blood, bile in sterile container on ice Actinomycosis /Actinobacillosis :Smears from pus lesions, pus in vial on ice

and formalin preserved material from affected muscle


134

Listeriosis : Aborted foetus, brain, placenta and all internal organs in 10% formalin on ice

CCPP/CCBP/Coryza : Swab from nasal or vaginal cavity in PBS and pieces of lung formalin and paired sera

Chlamydia/Psittacosis : Nasal swab, lung pieces in sterile tube and fixed smears from liver, lung & foetus

Mycotic Infections : Deep skins scrap in sterile vials Skin Diseases : Skin scrapings for identification of ecto-parasites & fungus

Viral Diseases :

RP/PPR/BVD: Anticoagulant blood at height of temperature/ Pre-scapular lymph node, spleen on ice and lung liver spleen or tonsils in 10% formalin or eye, mouth and rectal swabs in PBS on ice and pieces of intestine on ice

FMD: Vesicular fluid from unruptered oral vesicles and epithelial tissue from fresh lesions, oesophanrygeal fluid in 50% Phosphate Buffered Glycerin and Blood serum

Rabies: Hippocampus and brain in 50% Buffered glycerin and 10% formalin separately

Pox : Scabs in 50% Buffered glycerin and formalin separately Swine Fever : Heparinized blood from live animal or heart blood, pieces of spleen,

lymph node, pancreas in 50% Buffered glycerin BT or Septicemic blood in heparin/EDTA

Canine Distemper : Impression smears from liver and pieces of liver/spleen on ice in 10% formalin

ICH : Impression smears of liver fixed in methanol spleen, liver in sterile tube on ice and liver & kidney in10% formal saline

Canine Parvovirus Rectal swab in PBS or pieces of intestine,heart on ice and all internal organs in 10% formalin

Ranikhet Disease : Fresh dead/moribund bird on ice or portion of liver spleen trachea bronchi & lung in 50% Buffered glycerin or Proventriculus in 10% formal saline

Mareks Disease : Live bird in acute disease /Feather follicles from chest & neck intransport medium /Paired sera sample /portion of peripheral nerve, trachea, ovary, liver & spleen in 10% formalin

IBR : Live affected bird /Bursa in transport medium and in 10% Formalin / Paired sera sample(IB : Swab from the exudates lung and paired sera

Parasitic Diseases


134

Protozoan Diseases : Blood smears/ anticoagulated blood Gastro-Intestinal parasites: Faecal sample in 10% formalin/in dead animals’ (Round Worms 70% formalin) for identification and all internal organs in10 % in formalin

*****


134

ADVANCES IN ANTIMICROBIAL THERAPY OF OCULAR AILMENTS

M.VIJAY KUMAR

Ocular antimicrobial therapy differs from treating infections in other tissues because drugs can be administered directly to the eye, achieving high drug concentrations. However,owing to the limited number of veterinary ophthalmic preparations available for topical ophthalmic use, practitioners need to make rational antimicrobial choice and extralabel drug use for successful therapy.practitioners should avoid using the antimicorbials to treat noninfectious ocular conditions such as uveitis or allergic conjunctivitis.unwarranted antimicrobials have no affect on an antiiflammatory disease process and encourage antimicrobial resistance. Common bacterias affecting eye include Staphylococcus intermdius, Streptococcus spp.( Dogs), Chlamydophilia felis, Mycoplasma felis(cats), ,Streptococcus zooepidemicus, Pseudomonas spp., Aspergillus spp., Fusarium spp (Equines), Moraxella bovis (Cattle), Mycoplasma conjunctivae Branhamella ovis(Goats) and Chlamydophilia pecorum ,Branhamella spp (Sheep).

Routes of drug administration: The 3 primary methods of delivery of ocular medications to the eye are : Topical, Local ocular (ie, subconjunctival, intravitreal, retrobulbar, intracameral) and Systemic. The most appropriate method of administration depends on the area of the eye to be medicated - extraocular structures, cornea, anterior segment (anterior chamber and iris), posterior segment (ciliary body, retina, vitreous), and retrobulbar or orbital tissues. The conjunctiva, cornea, anterior chamber, and iris are usually best treated with topical therapy. In contrast, the eyelids can be treated with topical therapy but more frequently require systemic therapy. The posterior segment always requires systemic therapy, as most topical medications do not penetrate to the posterior segment.

1. Topical-most common route of administration :Degree of penetration of topically applied medications depends on integrity of normal defense mechanisms of the eye. Drug absorption is greatly enhanced by ocular inflammation. Medications put in the conjunctival sac can penetrate the cornea, conjunctiva, or be absorbed systemically via the nasolacrimal system It is also affected by the Vehicle, molecular size of the drug, drug concentration, pH, electrolyte composition and preservatives.

Corneal epithelium is the main site of resistance to drug penetration.. As a result, the epithelium and endothelium are relatively impermeable to electrolytes but are readily


134

penetrated by fat-soluble substances. Drugs that have the ability to exist in equilibrium in solution as ionized (water soluble; polar) and unionized (lipid soluble;nonpolar) forms are ideal for topical use, i.e., chloramphenicol, fluoroquinolones. Topical administration is used for treatment of eyelids, conjunctiva, cornea, iris, and anterior uvea. Following which , up to 80% of the applied drug(s) is absorbed systemically across the highly vascularized nasopharyngeal mucosa. Because absorption via this route bypasses the liver, there is no large first-pass metabolism seen after administration PO.

2. Subconjunctival (bulbar conjunctiva): This technique requires only topical anesthesia and a tuberculin syringe with a 25- or 27-gauge needle. Volumes should not exceed 0.25 ml in cats and dogs and 1.0 ml in horses and cows. Subconjunctival medication reaches the cornea by slowly leaking out of the injection site. Intraocular drug levels are attained by diffusion through the cornea and sclera. This is used for diseases of the cornea, anterior, uvea, anterior vitreous, and sclera.Drugs with low solubility such as corticosteroids may provide a repository of drug lasting days to weeks. Appropriate amounts must be used, as large amounts, especially of long-acting salts, can cause a significant inflammatory reaction. For sub-Tenon’s injections, 0.5 ml/site is usually safe and effective in small animals and ≤1 ml in large animals such as the horse and cow.

3.Retrobulbar medications:are used infrequently for therapeutics. In cattle, the retrobulbar tissues can be anaesthetized with local anesthetic (lidocaine) for enucleations. Whenever any medication is placed into the orbit, extreme care must be taken to ensure that the medication is not inadvertently injected into a blood vessel, the optic nerve, or one of the orbital foramen. Retrobulbar injection has a high risk of adverse effects and should not be used unless the clinician is experienced and the animal is appropriately restrained.

4. Intravitreal-used infrequently: Antibiotics,antifungal drugs have been effectively used in microgram dosages. Generally injected at the pars plana for infectious endophthalmitis.

5. Systemic-P.O., I.V. or I.M: Systemic administration is required for treatment of diseases of the retina, optic nerve, and vitreous., for posterior segment therapy and to complement topical therapy for the anterior segment. The blood-ocular barriers can limit absorption of less lipophilic drugs, but inflammation initially allows greater drug concentrations to reach the site. As the eye starts to heal, these barriers become more effective and can limit further drug penetration. This should be considered when treating posterior segment disease, eg, blastomycosis in small animals with hydrophilic drugs such as itraconazole.


134

Ocular dosage forms : Topical ophthalmic drugs are formulated as ointments, suspensions and solutions. Deciding which formulations to be used depends on the several practical considerations.Ocular contact time of ointment is longer than solutions or suspensions,so they are more practical when the owner cannot follow a frequent administration regimen.avoid ointments on penetrating wounds or descemetocele,and prior to intraocular surgery,as their petroleum base elicits severe granulomatous reaction when in direct contact with intraocular tissue. The frequency of topical application depends on disease and formulation.One drop of an antimicrobial solution applied four times daily is usally sufficient in uncomplicated corneal ulcers and bacterial conjunctivitis.When ointment is used a , 5mm strip is applied to the conjunctiva a minimum of three times a day. If more than one drug is involved in the therapeutic regimen,then 3 to 5 minutes should be allowed between application of each medication to avoid dilution or chemical incompatability.antimicrobial therapy is typically continued for seven days or until the ocular infection is resolved.

Antibacterial ocular drug therapy

Topical antibiotics are indicated for the treatment of corneal ulcers, corneal perforations, conjunctivitis,and blepharitis.. Ideal choice of appropriate therapy begins with identification of the organism and its sensitivity. Culture or cytologic examination of material from the affected area is necessary.Minor bacterial conjunctivitis infection may not justify routine culture and may be amendable to initial therapy with broad spectrum antibiotics. Normal ocular flora is predominantly gram positive;a predominance of gram negative organisms is indicative of an abnormal condition.

Chloramphenicol: Broad spectrum, bacteriostatic. Soluble in both water and fat so it penetrates intact cornea with topical administration-thus may be considered for initial treatment of intraocular infections (penetrates the cornea).it is good first choice antimicrobial for corneal ulcers and bacterial conjunctivitis.it is having poor efficacy against gram negative bacteria and pseudomonas spp.Frequency of administration- q4 hours for full therapeutic levels. Toxicity- risk of aplastic anemia

Aminoglycosides: a.. Neomycin: Usually found in combination with other antibiotics. Broad spectrum-bacteriocidal impairs protein synthesis.Frequency of administration-BID-TID. Toxicity- Topical-localized sensitivity; conjunctival irritant.Systemic-ototoxicity-possible head tilt. b. Gentamicin: Broad spectrum bactericidal activity including Streptococcus, Staphylococcus, Proteus spp, and Pseudomonas aeruginosa. Effective topically and subconjunctivally for external ocular infections. It is available as solution and ointment because of its chemical characteristics does not readily cross lipid


134

membranes,but readily enters the stroma when the corneal epithelium is damaged. Renal toxicity with concurrent oral therapy, may be toxic to surface epithelium. c. Tobramycin.: Two to four times more effective against Pseudomonas spp. and betalactamase producing staphylococci than gentamicin and effective against gentamicin-resistant microbes.

Polypeptides:a.Bacitracin: Bactericidal, active against gram positive microorganisms. Used in combination with other antibiotics. Poor corneal penetration. b. Polymyxin B: Poor penetration. Bactericidal. Effective mainly against gram-negative bacilli and Pseudomonas spp. Should not be given subconjunctivally.

Cephalosporins: a.Cefazolin: Broad spectrum, first generation cephalosporin.Topical use for gram + cocci resistant to other antimicrobials. Can be administered subconjunctivally-does penetrate intact cornea. Usually diluted to 50 - 100 mg/ml concentration. Mix with artificial tears to a concentration of 33 mg/ml for treatment of meibomitis

Fluoroquinolones: Eg: Ciprofloxacin ,Levofloxacin, Ofloxacin etc. Broad spectrum, active against gram positive and gram negative microorganims. Drug of choice for betalactamase producing staphylococcus and aminoglycoside resistant pseudomonas spp. Generally preferred in corneal, conjunctival, and intraocular infections. Excellent corneal penetration.not effective against streptococci spp. Because of their spectrum of activity these agents should never be used as empirical treatment.

Antiviral ocular drug therapy

The topical antiviral agents are static in action and topically irritating,so frequent dministration is necessary and client compliance and patient tolerance are issues.

Idoxuridine: Frequency of administration is 1 drop every 4hrs until corneal re-epithelialization occurs. Doesnot penetrate the cornea unless the epithelial barrier is broken. Acts by altering the viral replication by substituting for thymidine in the viral DNA chain therefore prolonged or too frequent administration may damage the corneal epithelium and prevent the ulcer healing.

Vidarabine: 3%Ointment-it is poorly lipid soluble,so corneal penetration is minimal unless ulceration is present.Penetrates the cornea better than Idoxuridine. Frequency of administration is to apply small amount of ointment 5 times daily until corneal re-epithelialization is complete,the every 12 hours for 7 days.


134

Trifluridine: 1%Solution-Current drug of choice for feline herpetic keratitis. Antiviral potency reported as over twice that of idoxuridine and 5 times greater than Vidarabine. s.penetrates the intact cornea,and ulceration and uveitis increase its intraocular penetration.; administered 4-8 times/day for 2 days, and reduced over next 2-3 weeks.

Antifungal ocular drug therapy

Topical antifungal agents are used more commonly to treat fungal keratitis in horses than in small animals. Penetration of the intact cornea is poor with all antifungals.

Polyenes : Natamycin : Used against Candida spp. and Fusarium spp. Amphotericin B: Fungistatic. Generally used systemically for fungal endophthalmitis. May be given as an intravitreal injection in mcg dosages.

Imidazoles. Miconazole 1%: the drug of choice for most veterinary fungal keratitis.Tolerated well as subconjunctival injection. 1 ml SID x 3-5 days if tolerated. Treatment frequency of a fungal keratitis may warrant 1 to 4hour treatment intervals.lotions or sprays that contain ethyl alcohol should not be applied to the eye. .Fluconazole is the synthetic triazole, fungistatic.currently drug of choice for topical use, subpalpebral lavage unit, and intracameral (100 μg) injection. Treatment for fungal keratitis may warrant 2 to 4hour treatment intervals.

Anti-inflammatory ocular drug therapy:

Corticosteroids: Subconjunctival injection of corticosteroids provide a greater local anti-inflammatory effect than can be achieved by topical or systemic administration. Posterior segment inflammation requires systemic corticosteroid therapy. In general, topical therapy should be continued two weeks beyond resolution of clinical signs. Local side effects of corticosteroid use include delayed corneal healing, increased corneal collagenase activity, and an increased incidence of bacterial and mycotic keratitis. In addition, topical corticosteroids may result in systemic changes. These include reduced baseline cortisol levels, suppression of the adrenocorticotropic hormone response curve, and altered carbohydrate metabolism. Frequency of administration-dependent on clinical signs and the type of steroid used..

Nonsteroidal anti-inflammatory ocular drugs : Some degree of GI intolerance may occur such as gastroduodenal ulceration and hemorrhage-when NSAIDs are used systemically.

Aspirin: dog-10 to 20 mg/kg, BID; cat-10 mg/kg, q 48 hours. Carprofen :. May have fewer side effects.Do not use in Labrador retrievers - may cause liver disease. Dosages:


134

2.2mg/kg BID. Not approved for use in cats. Etodolac :: dog-10 - 15 mg/kg, PO SID. Should not be used in dogs < 5 kg in the horse and dog , although not currently approved for use in dogs.: dog-0.75 to 1.20 mg/kg, IV, SID, not to exceed 2 days. Commonly given 30 minutes prior to surgery to minimize postoperative swelling and inflammation .; Not to be used. In cat. Flurbiprofen: Used topically preoperatively to stabilize the blood-aqueous barrier in inflammation (in diabetes mellitus), decrease production of ocular prostaglandins and maintain pupil size. Used to treat anterior uveitis and in the presence of corneal ulceration.

Ocular topical Anesthetics : To be effective, local anesthetics must have properties similar to drugs that penetrate the cornea. They must be capable of existing in ionized (water-soluble) and nonionized (lipid soluble) forms. Local anesthesia is less effective in inflamed tissue which has more acidic pH than normal. Most topical anesthetics are effective within 30 seconds to 3 minutes to facilitate procedures such as tonometry, corneal and conjunctival scrapings, and subconjunctival injections. Microbial cultures should be taken prior to application of topical anesthetics as inhibition of microorganisms has been attributed to topical anesthetic agents. The agents used are Proparacaine - 0.5%, . Tetracaine - 0.5% to 2%.. Topical anesthetics should not be used on a regular basis with painful eyes because: Animal may scratch off corneal epithelium (feels no pain) and may inhibit mitosis (thus healing) in corneal cells.

a. Osmotic Agents (topical) : 2-5% NaCl (hypertonic saline). Indicated primarily for treatment of severe chronic corneal edema originating from superficial epithelial disruption and for severe cornea bullae formation. Side effect-localized irritation.

b.Tear Film Supplements : Many tear film supplements currently exist today. All are indicated to control keratitis sicca. May provide temporary comfort to corneal irritation resulting from distichia, entropion, or sutures, and as a vehicle for delivery of medications. Tear supplements are available in solution and ointment form and are intended to replace the aqueous or lipid layer of the tear film. Preservative-free products generally recommended.

c.Lacrimogenics: These are drugs potentially capable of stimulating tear secretion.

1. Pilocarpine: May be effective in the rare case of neurogenic KCS. Prescribed as 2 drops of 2% Pilocarpine per 4.5kg body weight added to the food twice daily.

2. Cyclosporine A 0.2% ointment : Cyclosporine is a potent suppressor of T-cell growth factor and of the cytotoxic T-cell response to this growth factor.


134

3. Tacrolimus 0.02%, 0.03% ointment or solution : Effective alternative to cyclosporine. T-cell surpressor with a distinct receptor site to cyclosporine.

Anticollagenase/Mucolytic Agents :Collagenase inhibitors are indicated for the treatment of melting corneal ulcers. Acetylcysteine : Diluted from 10 to 20% with artificial tears to a 5 to 8% concentration. Administered every 1 to 4 hours until desired effect is achieved.

*****


134

CLINICAL PHARMACOLOGY OF BETA- LACTAM AND AMINOGLYCOSIDE ANTIBIOTICS

U.SUNILCHANDRA

The group of beta lactam of antibiotics includes Penicillins, Cephalosporins, Carbapenems and Monobactams.

PENICILLINS

Narrowspectrum penicillins : Acid labile penicillin(crystalline penicillin G / benzyl penicillin) and Acid resistant penicillins( penicillin V/phenoxymethyl penicillin and phenethicillin (phenoxy ethyl penicillin) are active specifically against gram-positive aerobes, facultative aerobes and obligate anaerobes. These can be still the drug of choice in infections : clostridial, listerial, actinomycosis, anaerobic infections (abscess, wound, pyothorax) and β-hemolytic streptococcal infections. Penicillin G is complexed with sodium or potassium salts for parenteral administration, which gives high concentrations of short duration with IV administration and lower concentrations of longer duration after IM administration. Penicillin G is complexed with procaine or benzathine for IM administration. Penicillin G procaine (PAM; aluminum monostearate- adjuvant used) by IM injection is more slowly absorbed than Penicillin G sodium salt. (An injection of 300,000 IU-adequate plasma levels for 24 hours). Benzathine Penicillin G, by IM route has the slowest rate of absorption. (frequency once in 72-96 hours). The availability of penicillin from procaine formulations is greater than from benzathine formulations. Plasma and tissue concentrations with procaine penicillinG are satisfactory for 12–24 h for most penicillin-sensitive organisms.

Antistaphylococcal penicillins (Cloxacillin, dicloxacillin, temocillin, nafcillin flucloxacillin, methicillin, oxacillin) have similar spectrum though with lesser potency, except that they are resistant to staphylococcalβ-lactamase. They are preferred in Staphylococcal skin infections in dogs, surgical prophylaxis, especially for orthopedic procedures and osteomyelitis

Broadspectrum penicillins: i) Aminopenicillins-ampicillin,amoxicillin(amoxycillin)and ampicillin prodrugs/precursors (bacampicillin, pivampicillin, hetacillin , talampicillin ii) Amidopenicillins eg: mecillinam (amidinopenicillin)

These have decreased activity against most of the gram positive species which are covered by the natural penicillins . They are slightly less active against gram-positive and


134

anaerobic bacteria than penicillin G but have greater activity against gram-negative bacteria. These are not active against penicillinase-producing Staphylococcus or gram negative bacteria that produce β-lactamases.They are used for soft tissue infections (non Staphylococcal)in dogs, cats and uncomplicated urinary tract infections.Aminopenicillins may not be used for surgical prophylaxis as Staphylococcus are common pathogens. Their spectrum of activity is extended to include some Gram negative bacteria, most notably: Hemophillus influenzae, Escherichia coli and Proteus mirabilis. They retain good activity against Neissaria species. Extended spectrum Penicillins: (Antipseudomonal penicillins): Carbenicillin and ticarcillin, in addition to gram negative coverage of aminopenicillins; have action against Pseudomonas, Enterobacter and Proteus species. Azlocillin, mezlocillin, and piperacillin,in addition, have spectrum against Klebsiella species. These (ticaricillin and piperacillin) are indicaited in the topical treatment of otitis externa due to P.aeruginosa resistant to other drugs and systemic treatment infections by Pseudomonas spp, usually in combination with an aminoglycoside .

Active secretion of penicillins can be blocked by probenicid, an uricosuric agent; which delays the excretion of penicillins, enhancing the duration of action.

Adverse Effects and Interactions: Hypersensitivity: Anaphylaxis (anaphylactic shock) – manifested by skin rash, hives, itching, difficulty breathing, shock, and unconsciousness. GI disturbances: diarrhea. nausea, vomition . Penicillins bind to and inactivate aminoglycosides, a form of chemical antagonism.They should never be administered simultaneously through the same I.V. line or through the same syringe. Carboxy- or Ureidopenicillins and aminoglycosides are synergistic in their anti-pseudomonas activity. Penicillin is synergestic with streptomycin. Antibacterials, bacteriostatic, such as: Chloramphenicol or Tetracyclin are antagonistic with penicillins.

CEPHALOSPORINS

Thee are wide-spectrum bactericidals exhibiting time-dependent efficacy .The agents are classified in to four generations, based on spectrum of antibacterial

First generation: Oral: cephalexin, cefadroxil, cefadrine, cephradine, cephaloglycin; Parenteral: cefazolin, cephapirin, cefalonium, cephalothin, cefacetrile, cefapirin, cefatrizine.

Characterestic Features: High activity against gram positive,Moderate activity against gram negative. Absorption being highly erratic in ruminants, thus being used only in


134

preruminant calves and small animals. poor penetration across barriers (such as blood brain barrier)

Cephalexin, cefadroxil and cefazolin : indicated for skin and soft tissue infections such as pyoderma caused by streptococci and Staph. Aureus. Cefazolin is used to treat bone and joint infections in the treatment of open fractures, lymphadenitis, abscesses, pharyngitis

Second generation: Oral: Cefamandole, cefotiam, ceforanide, cefonicid, cefmetazole, cefacetrile, cefotiam, cefranide, loracarbef, cefoxitin* cefotetan* (*-cephamycins); Parenteral: cefaclor, cefuroxime axetil, cefprozil, cefuroxime

Their use is reserved for infections, resistant to first-generation agents. Less efficacious than 1st generation against gram-positive pathogens; greater gram-negative spectrum of activity Relatively more resistant than first generation ,to β-lactamases, Poor penetration of the barrier. Cefoxitin and cefotetan (cephamycins): effective against gram negative anaerobes, are used in aspiration pneumonia, bite infections, ruptured intestine gangrene, peritonitis and pleuritis.

Third generation: Oral: cefsulodin, ceforanide, cefpodoxime proxetil, cefixime, ceftibuten, cefdinir, cefmenoxime, cefditren pivoxil, cefodizime, cefetamet; Parenteral: ceftiofur, cefotaxime, cefmenoxime, ceftriaxone, ceftizoxime, ceftazidime, cefovecin, cefoperazone, latamoxef* (moxalactam) , (* -cephamycin)

They exhibit high antibacterial activity; broader resistance to β-lactamases, though show moderate activity against gram-positive and are inferior in activity against Staphylococci. Ceftriaxone, ceftizoxime, cefotaxime and ceftazidime are effective in therapy for bacterial meningitis. Cefpodoxime has been used in skin infections of dogs

Ceftazidime,ceftriaxone and ceftizoxime and Cefoperazone are Antipseudomonal. Cefovecin is given as a single injection (SC), has about five days of elimination half life; used in dogs and cats to treat skin and soft tissue infections and urinary tract infections. It should not be used in less than 8 weeks old, renal dysfunction,breeding animals, pregnant and lactating dogs. Ceftiofur is indicated in bronchopneumonia of cattle (Pasteurella) Fourth generartion: Oral:. Cefmetazole, cefditoren; Parenteral: cefepime, cefpirome, cefquinome cefclidine, cefluprenam cefozopranThey have extended spectrum of activity against both gram positive and gram negative organisms ,greater stability against hydrolysis by beta lactamases. With excellent penetration ability in to CSF..


134

Adverse Effects: Gastrointestinal disturbances : Anorexia, vomiting and diarrhoea. Hypersensitivity reaction : manifested as urticarial rashes, fever, eosinophilia, angioedema and lymphadenopathy. ; avoided or used with caution in penicillin allergic individuals. Bleeding disorders: cefotetan, ceftazidime,cefamandole and cefoperazone : increased risk of bleeding due to a decrease in prothrombin activity and anti- vitamin K effects.Prophylactic vitamin K therapy is recommended if to be used for prolonged periods in malnourished patients.

Most of the the cephalosporins are synergistic with aminoglycosides. Antacids and H2-receptor antagonists: decrease the absorption of cephalosporins ; thus to be administered at two hours intervals. Nephrotoxic medications:, such as loop diuretics, especially in patients with pre-existing renal function impairment and Platelet aggregation inhibitors: (NSAIDS) may increase risk of hemorrhage if used concurrently with cephalosporins

PENEMS (CARBAPENEMS)

The carbapenems are more rapidly bactericidal than the cephalosporins and less likely to induce release of endotoxin in an animal from gram-negative sepsis. Examples: imipenem, meropenem faropenem.

Imipenem is a broad-spectrum antibiotic with excellent activity against gram positive and gram negative organisms (both aerobic and anaerobic), by comparison to third and fourth generation cepahalosporins.. It is resistant to most forms of beta-lactamase including that produced by staphylococcus. They are indicated in multiple-resistant gram negative or mixed aerobic and anaerobic infections, including those in immunocompromised hosts. Adverse effecst: GI disturbances, hypersensitivity reactions, seizures with high doses, renal failure or underlying neurological abnormality,infusion reactions such as thrombophlebitis after rapid infusion. They are synergistic with an aminoglycoside. and antagonistic with other β-lactam antibacterials, chloramphenicol .They are indicated for intra-abdominal infections, severe lower respiratory tract infections, septicemia ,bacterial meningitis ,osteomyelitis and life threatening soft tissue infections.

Dose: Imipenem-dogs ,cats- 5-10mg/kg, IV , IM, q 8 h; horse : 10-20mg/kg, IV, q 6 h .; Meropenem: dog- 2-5mg/kg, slow IV (with IV fluids) , q 6 h; 5 -10mg/kg, deep IM q 8 h or 8-12 mg/kg SC, q 8 -12 h.

MONOBACTAMS

Monobactams (Eg: aztreonam, tigemonam) are very beta-lactamase stable, with very narrow spectrum, only against aerobic gram negative organisms, can be used instead of


134

aminoglycoside drugs with less nephrotoxic side-effect . These do not cause GI disturbances Their inactivity against gram positive bacteria may lead to superinfection with yeasts and gram positive aerobes including Enterococcus spp.and S.aureus . Dose 30-50mg/kg,IV q8 h; indicated in wide variety of UTI. RTI, Septicemic infections.

BETA LACTAMASE INHIBITORS

Eg: Clavulanic Acid ( potassium clavulanate), tazobactam and sulbactam These drugs themselves have no antibacterial activity. They irreversibly inactivate bacterial beta lactamases, thereby enhancing the spectrum of activity of antibiotics used in combination with them. (amoxicillin ampicillin , piperacillin, ticarcillin and some cephalosporins). hese are often the drug of first choice for severe infections in skin,soft tissue and urinary tract and for surgical prophylaxis. Clavulanate is highly moisture sensitive, so precaution is to be taken to ensure the dryness of syringes for injection. Amoxicillin-clavulanic acid injection is not compatible with and should neither be reconstituted or mixed with dextrose / sodium bicarbonate solution nor it should be mixed with any other medication. The combination of tazobactam plus piperacillin has the broadest antoibacterial activity of the penicillins.

AMINOGLYCOSIDES

A post-antibiotic effect, i.e., residual bactericidal activity persisting after the serum concentration has fallen below the minimum inhibitory concentration (MIC), is a characteristic of aminoglycoside antibiotics; the duration of this effect also is concentration dependent. These properties usually makes the once-daily dosing regimens of aminoglycosides.

Narrow-spectrum : streptomycin and dihydrostreptomycin-against aerobic gram-negative bacteria; Expanded-spectrum : Neomycin, framycetin (neomycin B), paromomycin (aminosidine) and kanamycin have broader spectra than streptomycin that often include several gram-positive as well as many gram-negative aerobic bacteria.

In potency, the spectrum of activity and stability to enzymes of plasmid-mediated resistance is: amikacin > tobramycin ≥ gentamicin > neomycin > kanamycin > streptomycin.

Amikacin has the broadest spectrum of activity among the aminoglycosides, particularly important intreating serious Pseudomonas and other Gramnegative infections in immunosuppressed patients. It can be administered for 2–3 weeks at recommended doses with less risk of nephrotoxicity than with gentamicin.These aminoglycosides with


134

broader spectra that include P aeruginosa are often highly effective against a wide variety of aerobic bacteria and have no activity against anaerobic microorganisms/ in anaerobic conditions. Their action against most gram-positive bacteria is limited, and they should not be used as single agents to treat infections caused by gram-positive bacteria. In combination with a cell wall-active agent, such as a penicillin or vancomycin, an aminoglycoside (streptomycin and gentamicin most extensively) produces a synergistic bactericidal effect. Examples include septicemia; tracheobronchitis; pneumonia; osteoarthritis; and infections of the urinary tract, GI tract, and skin and wounds. Several aminoglycosides are used topically in the ears and eyes.

The treatment interval should be increased in neonates (especially puppies and foals), in renal failure, and in obese animals. Doses may be increased in animals with edema, hydrothorax, or ascites, provided their renal function is unimpaired. Because of their polar nature, they do not penetrate into most cells, the CNS, and the eye. High concentrations are found only in the renal cortex and the endolymph and perilymph of the inner ear; the high concentration in these sites likely contribute to the nephrotoxicity and ototoxicity caused by these drugs

Indications: Local and systemic infections caused by susceptible aerobic bacteria (generally gram-negative): bacteremia ,septicemia, bone and joint infections, enteritis (Neomycin sulfate: for enteritis caused by E. coli), respiratory tract, skin and soft tissue and urinary tract infections.

Dosages:

AMINOGLYCOSIDES:Kanamycin12-15mg/kg,IMorSC,SID-BID; Streptomycin/dihydrostreptomycin7.5-12.5 mg/kg, IM or SC, BID; Netilmicin3-6 mg/kg, IM or SC, SID- BID; Neomycin15 mg/kg, PO, SID- BID0.5-1 g/quarter, intramammary, SID ; Amikacin -IV, IM, SC 5-10 mg/kg q.12 h; Gentamicin IV, IM, SC 3-6 mg/kg q.24 h; Neomycin PO 10 mg/kg q.6 h; Streptomycin POIM, SC; 20 mg/kg q.6 h; 10 mg/kg q.12 h; Tobramycin IV, IM, SC 1–2 mg/kg q.8 hPENICILLINS: Narrow spectrum: penicillin G, Na, K IV, IM, SC 20,000–40,000 U/kg q.6–8 h; Penicillin G, procaine IM, SC 20,000 U/kg q.12–24 h Penicillin G, benzathine IM 40,000 U/kg every 3–5 days Penicillin V PO 10 mg/kg q.8 h Antistaphylococcal: Cloxacillin, flucloxacillin PO 10–40 mg/kg q.6–8 h Dicloxacillin PO 10–40 mg/kg q.8


134

Aminopenicillins: Amoxicillin PO, IV, IM, SC 10–20 mg/kg q.8–12 h; Ampicillin IV, IM, SC, PO 10–20 mg/kg q.6–12 h; amoxicillin-clavulanate : PO, IM, SC 12.5–25 mg/kg q.8–12 h .Antipseudomonal : Carbenicillin IV, IM, SC 50 mg/kg q.6–8 h Ticarcillin IV, IM, SC 50–75 mg/kg q.6–8 hInfusion: 15–25 mg/kg given over 15 min, then at constant rate of7.5–15 mg/kg/h Ticarcillin-clavulanate: IV Dogs: 40–110 mg/kg IV q.6–8 h; Cats: 40–75 mg/kg IV q.6–8 h

CEPHALOSPORINS: First generation Cefachlor PO 10–25 mg/kg q.8–12 h; Cefadroxil PO 10–30 mg/kg q.8–12 h Cefalexin PO Dogs: 20–40 mg/kg q.8–12 h; Cats: 22–50 mg/kg q.8–12 h; Cefazolin IV, IM 10–30 mg/kg q.4–8 h; Cefapirin IV, IM, SC, 10–30 mg/kg q.6–8 hSecond generation: Cefotetan IV 30 mg/kg q.6–8 h; Cefoxitin IV, IM, SC 10–30 mg/kg q.6–8 h; Cefuroxime IV, IM, SC 20–50 mg/kg q.8–12 hThird generation: Cefi xime: PO 5–12.5 mg/kg q.12 h; Cefotaxime: IV, IM, SC 20–80 mg/kg q.6–8 h; Cefovecin- SC 8 mg/kg (repeated every 14 days depending on indication); Cefpodoxime proxetil : PO 5–10 mg/kg q.12–24 h; Ceftazidime: IV, IM 20–50 mg/kg q.8–12 h; Ceftiofur : SC 2.2–4.4 mg/kg q.12–24 h; Ceftriaxone: IV, IM 15–50 mg/kg q.12–24 h Antipseudomonal: Cefoperazone: IV, IM 22 mg/kg q.6–12 h

*****


134

AN UPDATE ON MACROLIDES AND TETRACYCLINES

U.SUNILCHANDRA

The clinical pharmacological aspects of tetracycline, chloramphenicol, macrolide and lincosamide group of antibacterisla are briefed in this article.

TETRACYCLINES: are broad spectrum antibiotics,effective against organisms: which comprises- aerobic and anaerobic gram-positive and gram-negative, mycoplasmas, rickettsiae, chlamydiae, and some protozoa (amebae, babesia, theileria).

1.Short acting (half life 6 hours)-Tetracycline, chlortetracycline, oxytetracycline 2.Intermediate acting-half life 16 hours-demeclocycline Newer ones : 3.Long acting –half life-18-24 hours-doxycycline and minocycline. Tigecycline is the -newest, longest acting –half life-36 hours2

The tetracyclines are used to treat both systemic and local infections. General organ infections include bronchopneumonia, bacterial enteritis, urinary tract infections,metritis, mastitis, prostatitis, and pyodermatitis. infectious keratoconjunctivitis in cattle, chlamydiosis, anaplasmosis, actinomycosis, actinobacillosis, nocardiosis (minocycline), ehrlichiosis( doxycycline), eperythrozoonosis, and haemobartonellosis. . As additives in animal feeds, they serve as growth promoters.

Adverse effects: High doses (PO) in ruminants disrupt microflora, eventually producing stasis. Elimination of the gut flora in monogastric animals reduces the synthesis and availability of the B vitamins and vitamin K from the large intestine. Tetracyclines chelate calcium in teeth and bones; they become incorporated into these structures, inhibit calcification (eg, hypoplastic dental enamel), and cause yellowish then brownish discoloration. At extremely high concentrations, the healing processes in fractured bones is impaired. Rapid IV injection of a tetracycline can result in hypotension and sudden collapse. This effect can be avoided by slow infusion of the drug (>5 min) or by pretreatment with IV calcium gluconate. The IV adm. of undiluted propylene-glycol-based preparations leads to intravascular hemolysis, which results in hemoglobinuria, and other reactions such as hypotension, ataxia, and CNS depression The combined use with glucocorticoids leads to weight loss, particularly in anorectic animals . The tetracyclines are potentially hepato and nephrotoxic and are contraindicated (except for doxycycline) in renal insufficiency.


134

Interactions: The absorption from the GI tract is decreased by milk and milk products, antacids, kaolin, and iron preparations. Tetracyclines gradually lose activity when diluted in infusion fluids and exposed to ultraviolet light. B-complex Vitamins , especially riboflavin, hasten this loss of activity in infusion fluids. Tetracyclines bind to the calcium ions in Ringer’s solution.. The tetracyclines are less active in alkaline urine, and urine acidification can increase their antimicrobial efficacy

Tigecycline: is a glycylcycline.; broad antimicrobial spectrum; effective against many tetracycline resistant organisms: Staph, MRSA, vancomycin intermediate and ncomycinresistant strains, G+ve rods, enterobacteriaceae, multidrugresistant acinetobactersp, anaerobes (G+ve, G-ve), atypical agents, ricketisiae, chlamydia, legionella, rapidly growing mycobacteria.Used in multi drug resistant nosocomial pathogens (MRSA, beta lactamaseG –sp) and skin and intraabdominal infections. Not indicated for urinary tract infections.

CHLORAMPHENICOL: Broad spectrum bacteriostatic. With specific activity against a wide variety of organisms (gram +ve and –ve and anaerobes gram-positive cocci and clostridium species;gram-negative rods ,. staphylococci and streptococci;some gram-negative organisms, such as Bordetellabronchiseptica, Escherichia coli, and Salmonella species;anaerobic bacteria; and rickettsiae Adverse effects: Hematological toxicity (aplastic anemia: leukopenia, thrombocytopenia, bone marrow depression). Indications: Anaerobic infection-meningitis,Brain abscess-used together with penicillin. ; Intraocular infection-Topical use in conjunctivitis, and external ear infections; as second choice drug in: rickettsial infection and brucellosis. Dose: Dogs:, 45- 60 mg / kg body weightPO,IM,IV,SC q8h; cats- 13 to 20 mg/ kg,PO,IM, q12h MACROLIDES: are bacteriostatic,(bactericidal at high concentrations.). In general, they have a spectrum similar to that of the penicillins and are often used as penicillin substitutes for the treatment of streptococcal and staphylococcal infections.In addition,against Mycoplasmae, Chlamydiae, Legionellae, Rickettsia spp. gram positive anaerobes etc..

Interactions: Macrolides should not be used with chloramphenicol or the lincosamides. Activity of macrolides is depressed in acidic environments. Macrolide preparations for parenteral administration are incompatible with many other pharmaceutical preparations. Erythromycin and troleandomycin are microsomal enzyme inhibitors that depress the metabolism of some drugs like warfarin, theophylline, carbamazepine and methyl prednisolone. terfinadine, azole antifungals, cisapride


134

Tilmicosin is used treatment of pneumonia in cattle, sheep and pigs, associated with Pasteurella haemolytica, P. multocida, Actinobacillus pleuropneumoniae, mycoplasma species Tilmicosin phosphate has been effective for treating: .bovine respiratory disease (as effective or more effective than other established treatments: ceftiofur, oxytetracycline, or florfenicol). Injections to horses, goats, swine, or nonhuman primates can be fatal. heart ,the target of toxicity via depletion of cardiac intracellular calcium, resulting negative inotropic efect. As a feed additive , it is effective for controling pneumonia in swine. When injected in swine, tilmicosin has caused toxic reactions and death due to cardiovascular reaction. Dose: Cattle and sheep: 10mg/kg, SC, every 72 hours; Pigs: 200-400g/tonne feed

Tylosin is therapeutically used to treat: swine dysentery, pleuropneumonia, colitis in dog, other infections in cats, chickens Mycoplasma canis and Mycoplasma haemocanis infection in dog,cattle Tylosin is alos used for growth promotion in pigs, cattle, and chickens. Dose: Dogs: 40mg/kg,PO,tid; cats 4mg/kg,IM,sid; Cattle: 10-20mg/kg,IM,bid; Pig: 10mg/kg, IM, bid,25g/100litres drinking water,100g/tonne feed;Poultry: 10 mg/kg, IM, sid-bid 7-10 mg/kg, PO, tid ; 50g/100litres drinking water

Clarithromycin possess broad spectrum bactericidal activity ,with more activity against mycobacterial avium complex and post antibiotic effect with very good activity against opportunistic infections in Toxoplasmosis, Cryptosporidiosis; H.pylori in peptic ulcer. High concentration in the alveolar macrophages, lung tissue and tonsillar tissue show high penetration of the drug into the respiratory tract cells, a feature that enhances efficacy against typical and atypical pathogens causing pneumonia It is more acid stable, more active against mycobacterium avium complex with lower frequency of GI intolerance. Dose: Dogs and cats: 5-10mg/kg,PO, bid Azithromycin is slightly less active than erythromycin against staphylococci and streptococci and slightly more active against Haemophilus influenzae.; good activity against many intracellular organism. (Chlamydia, Toxoplasma) , mycobacteria ,mycoplasma ; but not against enteric gram-negative bacteria or Pseudomonas. The features: better oral absorption,better tolerance,longer half-life ,higher tissue concentration, broader spectrum of activity and lesser drug interactions . Dose: Dogs : 5-10mg/kg,PO, sid ; cats: 5mg/kg.PO, once daily or every alternate day. Roxithromycin is a longer acting and more stable: Dogs : 15mg/kg,PO, sid

Tacrolimus is a macrolide ; is an immunosuppressive with similar mechanism of action as another immunosuppressant, cyclosporine to inhibit T lymphocyte proliferation. It has topical anti inflammatory effects without the atrophogenic effects and metabolic effects of topical GC. It is used topically for the treatment of atopic dermatitis,psoriasis ,


134

alopecia areata and effective in canine perianal fistula and localized lesions in diseases like discoid lupus erythematosus, pemphigus erythematosus, pemphigus foliaceous.

LINCOSAMIDES: bacteriostatic/ bactericidal depending on the concentration/; particularly active against grampositive,mycoplasma, and anaerobes(most aerobic gram-negative bacteria are resistant). The agents are lincomycin and clindamycin. The antimycoplasmal activity of the lincosamides(clindamycin > potent) is similar to that of erythromycin but less than that of the other macrolides. In horses,rabbits, chinchillas, guinea pigs, neonates and hamsters: these are contraindicated due to risk of gastrointestinal adverse effects like serious fatal enterocolitis and diarrhoea. Ruminants exposed to oral lincomycin : anorexia, ketosis, and severe diarrhoea.

Interactions: Additive neuromuscular effects with anesthetic agents and skeletal muscle relaxants. Antidiarrheals,adsorbent (kaolin/astringent) significantly decrease absorption..

Indications: lincomycin HCl: respiratory tract, skin and soft tissue,dental infections, osteomyelitis (cats, dogs) ; swine dysentery, joint infections (pig); necrotic enteritis (chicken); clindamycin: severe anaerobic,respiratory infections . Dose: Lincomycin: 10 mg/kg, IM, bid- Cattle,pig,cats; 20 mg/kg, PO, sid- dog.; Clindamycin: 5-10 mg/kg, PO, bid- Dogs, cats

*****


134

ADVANCES IN ANTIMICROBIAL THERAPY OF MASTITIS

N.A. PATIL

Bovine mastitis is internationally recognized as one of the most economically important disease confronting the dairy industry. The disease not only decreases the quantity, but also reduces the quality of the milk, thus resulting in significant losses to the dairy farmer. The loss is further enhanced by the cost of the treatment and culling of animals due to permanent damage of quarters in certain cases. The key to combat losses due to mastitis is the early detection, accurate diagnosis, treatment and suitable control measures are to be undertaken.

Diagnosis : The various diagnostic tests that can be employed for detection of mastitis are

1. Strip cup plate test

A black surface strip plate is invariably used. Although, flakes and clots may be palpable or obvious on other surfaces, serum like or watery milk is appreciated on a black surface stripped plate.

2. PH indicator strips

Determination of milk pH is done by using specially prepared filter papers containing bromothymol blue, bromocresol purple etc. Mastitis is characterized by a change in pH towards alkalinity, though this change may not be present in the early stage of mastitis. Normal PH is 6.5 to 6.7 or 6.0 to 6.4 in colostral milk. It is around 6.0 in gangrenous mastitis and greater than 6.9 in other forms of mastitis.

3 White side test

Five drops of milk are mixed with 2 drops of sodium hydroxide solution on a microscope slide. If the milk is normal and has a normal cell count, homogenous turbidity develops within 2 - 3 seconds. If the cell count is high, flakes form and the mixture become stringy.

4. California mastitis test


134

Two ml of milk from each quarter are placed in the four dishes of a black or white test plate. 2 ml of the reagent is added to each dish and the contents are mixed by slow circular movements. The results are read after 10 seconds.

Negative Mixture remains liquid. No precipitates

Trace Precipitates tends to disappear with movement of paddle

1+ Distinct precipitates. No gel formation

2+ Gel becomes thick and lumpy

3+ Gel adheres to the bottom of the paddle

The principle of the test is the ability of surface active substances to dissolve leukocytes and their nuclei, liberating DNA from the latter. The DNA forms a complex with the reagent that appears as a gel.

5. Chloride test

In a normal milk chloride level varies from 0.08 to 0.14 per cent. Due to inflammatory exudate, abnormal milk have high chloride levels. The chloride level may be estimated by addition of 5 ml of 0.134% silver nitrate solution and 2-3 drops of 10% potassium chromate solution. Yellow color indicates chloride level more than 0.14% and brownish red color indicates less than 0.14% level.

6. Catalase test : examined by evolution of oxygen on adding 1 ml of 3% H2O2 to 9 ml of milk.

7. Electrical conductivity

The test which has received more attention is based on increase in sodium and chloride ions in mastitis milk and thereby increase in electrical conductivity. Electronic sensors with shielded electrodes are used and hand held devise with a built in cup into which milk is squirted

8. Serum albumin concentration in milk

This test set out to access the integrity of mammary mucosa. Radial immunodiffusion test (RID) called as mono mast test is employed.

9. NAGase test


134

This test is based on measurement of cell associated enzyme ( N-acetyl-beta D-glucosaminidase) in the milk. High level of the enzyme indicates high cell count and it is the most accurate as somatic cell count and they are high at the beginning and end of lactation.


134

10. Antitrypsin test

This test measurers trypsin inhibitor capacity of milk. This is high at the beginning of lactation due to antitrypsin activity of colostrums, but after the first month of lactation this activity is due to solely to serum antitrypsin activity which has leaked through damaged epithelium.

Treatment

Clinical judgment to distinguish between mastitis caused by Gram positive or Gram negative pathogens are not accurate. To select cows for antimicrobial therapy on the basis of bacteriogical culture is costly and delays treatment, clinical judgment would still be necessary because bacteria are not isolated from 15-40% of milk samples from cows with clinical mastitis. The first decision to make whether to treat parenterally or by intramammary infusion or both or not at all.

Parenteral antimicrobial therapy should be considered in all cases of mastitis in which there is a marked systemic reaction and swollen udder in which intramammary infusions are unlikely to diffuse to all parts of the glandular tissue. To achieve therapeutic levels of an antimicrobial in the mammary gland, it is necessary to use higher than normal dose rates daily for 3-5 days

Udder infusions are preferred because of convenience and efficiency. Cure rates are very high with infusions in cases of mastitis caused by Str. agalactiae. The degree of diffusion in to glandular tissue is the same when either water or ointment is used as a vehicle for infusion. Strict hygiene is necessary during treatment to avoid the introduction of bacteria, yeast and fungi in to the treated quarters. Use only a short canal that can just penetrate the external sphincter. Complete emptying of the quarter by the parenteral injection of oxytocin followed by hourly hand stripping of affected quarters before infusion is advisable in case of clinical mastitis.

Selection of antibiotics:

The Selection of antibiotics for therapy has been the basis of important criteria of sensitivity of the pathogens and the pharmacokinetic properties of the drugs. It is necessary to know something about their diffusion in to mammary tissue, the degree of binding of a drug to mammary tissues and secretions, the ability to pass through the lipid phase of milk and the degree of ionization. For lactating cows the preferred treatment is one which maintains a minimum inhibitory concentration (MIC) for 72 hours without the need for multiple infusion and without prolongation of the withdrawal time


134

The aminoglycosides neomycin and framycetin, ampicillin and amoxicillin and especially newer generation of cephalosporins are the drug of choice for use in cases in which infection may be caused by either a gram positive or gram negative organism. Penicillin is favoured for Gram positive infections. The drugs which have the best record of diffusion through the udder after intramammary infusion are ampicillin, amoxicillin, erythromycin and tylosin. Medium performance are pencillin G, cloxacillin and tetracyclines. Poor diffusers, which do have a longer half life in the udder because they bind to protein include streptomycin and neomycin.

In coliform mastitis antibiotics like gentamycin, amikacin, cephalothin, trimethoprim plus sulfadoxine, amoxicillin plus clavulanic acid is recommended as these have been claimed to be more effective.

Non steroidal anti-inflammatory ( NSAIDS) have the beneficial effects on the severity of clinical signs such as body temperature heart rate, size of the udder and pain associated with the mastitis. Meloxicam, flunixin meglumine (2.2mg/ Kg), flurbiporfen (2mg/kg, I/V) and Dexamethasone (1mg/kg, I/V) can be used as anti-inflammatory agents.

Supportive therapy including balanced electrolyte solutions containing 5% glucose at the rate of 100-150 ml/kg body weight per 24 hours by continuous intravenous infusion is indicated in cases where extensive tissue injury and severe toxemia are present. Antihistamines may be used to reduce toxaemia. Application of cold (crushed ice) in a canvas bag suspended around the udder may reduce the absorption of toxins. Injection of selenium and vitamin E may enhance the resistance of the mammary gland to infectious agents. Tri-sodium citrate given at the rate of 30mg/kg orally once a day for 10 days has been claimed to be effective in treatment of mastitis.

Control :The specific components of mastitis control program must be devised to fulfill three basic principles

Elimination of existing infections by detection and treatment of infected quarters during lactation and dry period and culling of chronic cases.Prevention of new infections achieved by good managemental practices,administration of vitamin E-3000mg of 5 to 10 days prior to calving, in diet at the rate of 4000 I.U. During last 14 days and 2000 IU during lactation decrease the incidence of infection. Monitoring udder health status: To reduce the new infections dipping of all teats after each milking should be done. Environmental and nutritional management have also become important for the prevention of new infections.


134

*****


134

CHEMOTHERAPUETIC PROTOCOLS IN HEPATIC AILMENTS

M. VIJAY KUMAR

Liver has very complicated functions and one of the most important function is the detoxification of drugs such as antibiotics and its metabolites. Some antibiotics can cause allergic reactions while others can cause direct damage to their liver, which can be quite severe in patients with chronic liver disease. For patients with a pre-existing liver disorder, the detoxification function of the liver is already compromised and substances that would normally be metabolized could actually accumulate in the liver or in the bloodstream.Liver disease may have a variable effect on drug clearance. There are no tests for hepatic function that will reliably predict drug clearance.

Antibiotics that accumulate in this manner could become toxic to the body and its functions can change drastically from its original purpose. For the most part in treating patients with preexisting liver disease who develop infections outside the liver, one should use caution in prescribing drugs known to be dependent on liver for inactivation or excretion. Usually a safer substitute drug can be found. If a potentially toxic drug must be used, blood levels can be useful in monitoring the dose to within safe limits. One should also take care to avoid use of hepatotoxic non-antibiotic drugs concomitantly. On the other hand, drugs metabolized and/or excreted by the liver are theoretically ideal for treatment of acute infections of liver and biliary tract. Each one of the ollowing antibiotic is ordered according to their potential harmful effects on the liver, the top group being the most potentially harmful and the last group being the least.

Tetracyclines: Used in larger doses, cause jaundice, fever, and fatty liver. Hepatitis patients should not be administered with these agents. All tetracyclines are concentrated in liver and excreted via bile into intestine, where they are reabsorbed. Variable amounts of each member of this drug family are thereafter eliminated in urine.; have prolonged half-lives in the serum because of slower renal clearance than that of tetracycline or oxytetracycline. With excess parenteral dose, liver toxicity progresses to acidosis, shock, coma and death.Other organs which may suffer simultaneous toxicity are pancreas, kidneys and brain. Pregnancy and chronic renal disease seem to predispose patients to this type of hepatotoxicity. Dosage adjustment is necessary, avoid exceeding a blood level of 10mcg/ml. Tetracyclines have adverse effects on several hepatic enzymes. Inactivated chlortetracycline causes same toxic hepatic changes as the active drug, so hepatic toxicity


134

appears not related to antibacterial activity; thus to be avoided completely in liver disease

Macrolides : Erythromycin: It causes damage to the liver via cholestasis (bile retention) and jaundice. The harmful effects usually start to show after 10 to 14 days use and the incidence rate is approximately 5 to 10%. Clinically, patients may develop abdominal pain, nausea, vomiting, jaundice, and elevation of liver enzymes. These conditions are often considered allergic reactions since the incidence rate is not very high Liver toxicity is caused by only estolate form. Avoid estolate form in liver disease and other forms in usual dosage. Estolate-induced hepatitis is a dose dependent. hypersensitivity reaction.

Lincosasmides: Lincomycin: is excreted and re-excreted via enterohepatic circulation. Bile levels are high upto 10-20x the serum level. Occasional jaundice and/or abnormal liver function tests which clear rapidly, sometimes even while drug is continued. Half-life of drug is doubled in liver disease accordingly drug dose should be reduced, or drug avoided entirely.

Kanamycin : Not Metabolised by liver.No change in dose in case of parenteral liver disease.in case of oral dose kanamycin at 8 Gm/day eventually builds serum levels to therapeutic range. This effect is even greater with hepatic disease and azotemia. Accordingly, such patients on gut sterilization with kanamycin should be watched for deafness and increasing nephropathy. Neomycin: Not metabolised by liver. No more than 6 Gm P.o in liver disease for gut sterilization. If azotemia also present,kanamycin is preferred.

Chloramphenicol: When metabolized in the liver, they combined with glucoronic acid and lose their anti-microbial effects. This combination of antibiotics and glucoronic acid can accumulate in the bloodstream, which can cause bone marrow inhibition. As a result, WBC and RBC counts can drop and patients with hepatitis should try to avoid this group if they can. Metabolism by liver. 85-95% is conjugated in liver to monoglucuronide and 3% is further converted to aryl amines and aryl nitro derivatives.Most of above is secreted then by kidney tubules. Significant concentration in liver tissue levels and average bile levels,that of plasma. Liver toxicity is rare. Use with caution in liver disease. If ascites or jaundice is present, use under 25 mg/kg/ day or another drug. Newborns are vulnerable to "grey syndrome"due to immature hepatic and renal function.


134

Penicillins: These antibiotics cause the least liver damage and only patients who are allergic may experience some side effects. Generally, antibiotics in the penicillin family are the most "liver friendly" and safe for chronic hepatitis patients to use.

Penicillin G: . Metabolism by liver: Only minor fraction is ordinarily handled by liver, but in impaired renal function the liver may be a major excretion route via bile. Attains significant liver tissue levels and also bile levels.Liver toxicity is rare, as part of a generalized hypersensitivity reaction. No change in dose in liver diseases if renal function is good and reduce dose in circumstances of combined kidney and liver disease.

Generally the information for penicillin G applies also for Alpha-phenoxy-peniclllins Methicillin., Oxacillin methicillin. Cloxacillin and broad spectrum penicillins: ampicillin, hetacillin, carbenicillin and nafcillin.

Streptomycin and Dihydrostreptomycin: Metabolism by liver.Small fraction is secreted into bile. Bile levels up to 10-20mcg/ ml on high doses. Liver toxicity is rare and also may aggravate existing liver disease. No change in dose in liver disease.

Cephalosporins: Cephalothin: Metabolism by liver, 70-80% usually excreted unchanged in urine. However, it can be inactivated by deacetylation (presumably in liver), then excreted in urine. Advisable to decrease in presence of combined renal-hepatic disease.

Nitrofurantoin: Metabolism by liver: 50-60% is metabolized at unknown site. Rarely, causes a hypersensitivity hepatitis with cholestasis, focal necrosis, infiltrates,eosinophils.

Sulphonamides: Metabolism is significantly, but not solely by liver (acetylation, glucuronidation, and/or oxidation), then excreted into urine. Not influenced by dose: direct hepatotoxicity and hypersensitivity. Either may go on to acute yellow atrophy. Best to avoid dose in liver disease. Pre-existing nutritional liver disease may predispose to sulfonamide hepatotoxicity. Kidneys appear to be more susceptible to damage by sulfas in patients with chronic liver disease.Neonate require less dose for therapeutic blood levels.

Metronidazole and related drugs (tinidazole, ronidazole): are sometimes used in patients with hepatic disease because of the anaerobic spectrum. The most serious problem caused by high dose of metronidazole has been attributed to CNS toxicity and include seizures, ataxia, nystagmus, tremors, and rigidity.4 These signs have been attributed to inferring with the inhibitory neurotransmitter GABA. Because animals with hepatic disease also may be prone to CNS disorders that also share these clinical signs, veterinarians should


134

understand the risks of metronidazole, and become familiar with the signs associated with toxicity.

Fluoroquinolones: The fluoroquinolones (enrofloxacin, marbofloxacin, orbifloxacin, difloxacin) have had a good safety record and increased risk of toxicity in animals with hepatic disease has not been documented. Although some of these drugs are metabolized, the clearance is low and probably not affected unless there is substantial loss of hepatic function. These drugs are also cleared by the kidneys

A common dilemma for veterinarians is which nonsteroidal antiinflammatory drug (NSAID) to administer to a patient with hepatic disease. The six approved NSAIDs for dogs: carprofen, etodolac, Meloxicam (cats), tepoxalin, deracoxib, and firoxixib. Because studies have not been conducted in animals with hepatic disease, there is no single drug shown to be safer than another. However, All NSAIDs have the potential to: (1) induce liver injury. (2) Pre-existing elevations in liver enzymes has not been shown to increase an animal’s risk for NSAID-induced liver injury, but a sharp increase in liver enzymes and/or bilirubin after instituting NSAID therapy is cause for alarm. (3) cause gastrointestinal injury, including erosions, ulcers, and bleeding. Patients with hepatic disease have an increased risk of these problems. (4) There is no NSAID yet to be shown safe for long-term administration for cats and hepatic reactions have been one of the problems associated with NSAID administration in cats. Tramadol and opiate analgesic drugs have high clearance and their metabolism is not likely to be affected by a loss in hepatic function or changes in hepatic enzymes. These drugs have a high safety margin and can be used safely in patients with hepatic disease.

*****


134

ADVANCES IN THERAPEUTIC PROTOCOLS IN VETERINARY ONCOLOGY

B.V.SHIVA PRAKASH

The effectiveness of a chemotherapeutic agent is measured in terms of concentration and exposure time. Routes of administration and absorption may influence the efficacy of an administered drug.The chemotherapeutic agents can be administered orally, subcutaneously, intramuscularly and intravenously for systemic effects.Local effects can be obtained by topical,intrapleural/peritoneal ,intra cystic/intrathecal into the CSF.All the chemotherapeutic agents can not be given by each and every route hence proper selection of route of administration can maximize the efficacy . Biotransformation of the drug also should be taken into consideration in chemotherapy.Prednisone used in chemotherapy has to be converted into prednisolone by the liver to be effective. Distribution of drugs partially determines its effectiveness. If the drug donot reach to the tumour,the exposure of tumour cells to chemotherapeutic agent will be nil. Some drugs will be effective during first time administration while they may not be so effective during their subsequent administration Drug resistance may develop by several means such as acquired resistance of the tumour may occur owing to decreased activation or increased deactivation of drug reducing its effective contact time..Toxicity: GI toxicity, bonemarrow suppression and immunosuppression.

Principles of combinations of chemotherapy: 1. Effective single agent used. 2. Two drugs with different mechanisms of actions should be used. 3. Intermittent treatment schedule

Guidelines for chemotherapy: Thorough clinical examination, history collection and appropriate data base are necessary for chemotherapy.

1. Histological diagnosis of tumour is must to know whether it is begnin or malignant

2. Biological behavior of tumors should be understood

3. Drug toxicities,dose level ,species limitations should be understood.

4. Monitoring of toxicities is essential.

5. Therapy should be undertaken with properly explaining the pros and cons to the owners.


134

Chemotherapeutic agents can be classified as : 1. Alkalyting agent’s 2.Antimetabolites 3.Plant alkaloids 4. Antibiotics 5.Hormones 6.Miscelaneous

1. Alkalyting agents: These are the compounds that substitute an alkyl radical (R-CH2-CH2

+) for hydrogen atom on some organic compounds. These agents interfere with DNA replication and RNA transcription.There are five class of alkylating agents

a) Nitrogen mustard derivatives: Methchloethamine,Cyclophosphamide,Chlorambucil and Melphalan; b) Ethenimine derivatives:Triethylenethiophospharamide; c)Alkyl Sulfonate:Busulfan d) Triazene derivatives:Dacarbazine; e) Nitrosoureas: Carmustine, Lomustine, and Somustine

Cyclophosphamide is the most commonly used alkylating agent in Veterinary practice.It is used for lymphoreticular neoplasms,carcinomas,mast cell tumour,TVT,Cyclophophamide requires activation to its active metabolite 4-hydroxy Cyclophosphamide by liver.Dose 50mg/ M2 per orally or weekly once for four times intravenously. Chlorambucil is used in canine lymphosarcoma.Dose rate is 2mg/ M2 Per orally or at weekly intervals for two to four weeks.

2. Antimetabolites: The antimetabolites are structural analogues of normal metabolite required for cell function and replication.They damage cells by interacting with cell enzymes (1).By substituting for a metabolite needed in key molecule,rendering it functionally abnormal (2.)By competing successfully with a normal metabolite that acts at an enzyme regulatory site to alter the catalytic rate of a key enzyme.

The important antimetabolite drugs are Methotrixate, 6-Mercaptopurine,)5-Flurouracil and Cytosine Arabinoside. The antimetabolite drugs are S-phase specific.

Methotrixate acts in S-phase to inhibit dihydroxy foliate reductase compitatively and interferes with both DNA and RNA synthesis.The folic acid antagonists are used in the treatment of lymphoreticular neoplasms,myeloproliferative disorders,transitional metastatic cell tumours,TVT,sertoli cell tumour and ostesarcoma.Methotrixate dose 2.5mg/ M2 per orally daily until response or toxicity.

3.Plant alkaloids: Vincristine and Vinblastine are the alkaloids extracted from the periwinkle plant.Vinca Rosea.They act specifically in M phase by binding with microtubular protein tubulin and blocking mitosis by interfering with chromosomal separation in metaphase.Both the drugs are used in the treatment of lymphoreticular neoplasms Vincristine is the treatment of choice for TVT and has been used for the treatment of carcinomas and mast cell tumour.


134

4.Antibiotics : They are derived from soil fungus( Streptomyces).They are cell cycle non –specific drugs.They damage the DNA.Inhibit DNA or RNA synthesis.Doxorubicin is a cytotoxic drug.Vomiting,diarrhea,myelosuprression,cardiac toxicity are the side effects.Doxorubicin must be given slowly when given intravenously.Pretreatment with histamine helps in avoiding complications.Dose:30mg/ M2 at three week interval for TVT,lymphosarcoma,carcinoma.

5.Hormones: Peptide hormones convert ATP to c-AMP(cyclic AMP).c-AMP is a secondary messenger to deliver and amplify signals to intracellular site.Steroid hormones enter cell and bind to specific receptor protein. “Transformation” (activation) of this newly formed complex allows it to pass the nuclear membranes where it binds to DNA.This binding alters transcription of cell messenger RNA,resulting in synthesis of new protein.Steroid induced increase in fatty acids may cause dissolution of the nuclear membrane,leading to cell death.

Adrenal corticoids are used for treatment of lymphosarcomas and mast cell tumours.Sex hormones are used in the treatment of mammary ,prostate and perineal gland tumours.Hormones have valuable role in replacement therapy following abalation surgery,in the management of some metastatic problems.Prednisolone 60 to20mg/ M2 per orally every 48 hours used in Lymphoreticular tumors mast cell tumour,and CNS tumours.Diethyl Stilbestrol 1.1mg/kg (not more than 25mg)- used for perianal adenomas, prostatic tumours.

6. Miscellaneous agents: examples: L-Asparginase o,p-DDD. L-Asparginase enzyme preparation is derived from the bacteria.L-asparginase deprives the neoplastic cells that lack the ability to synthesise L-asparginase of extracellular source there by inhibiting protein synthesis.L-asparginase acts against cells in G1 phase.Used for the treatment of lymphoreticular neoplasms @20,000units/ M2 intraperitoneally.Side effects are anaphylaxis and leukaemia. o,p-DDD: Directly suppresses normal and neoplastic adrenocortical cells,used in adrenocortical insufficiency @50mg /kg PO, to effect.

Drugs used in Chemotherapy:Chemotherapeutic agents dose is expressed in terms of mg per square meters of body surface area.This is physiologically more accurate method of determining the dose.Weight in grams is converted to body surface area(meter square)

as follows: M2 = Km xW2/3 / 104; wherein: M2 - Body surface area in square meters; W-

Weight in grams; Km- Species specific constant (10 for cats and 10.1 for dogs).The relation of body weight to surface area in square meters for dogs is given in this table:


134

Kgm2

Kg

m2

kg m2 Kg

m2

kg m2

0.5 0.06 6 0.33 12 0.52 18 0.69 24 0.83

1 0.10 7 0.36 13 0.55 19 0.71 25 0.85

2 0.15 8 0.40 14 0.58 20 0.74 26 0.88

3 0.20 9 0.43 15 0.60 21 0.76 27 0.90

4 0.25 10 0.46 16 0.63 22 0.78 28 0.92

5 0.29 11 0.49 17 0.66 23 0.81 29 0.94

DRUGS MAJOR INDICATIONS Dose& Route of Admn.

Cyclophosphamide Lymphoma,sarcomas, mammary adenocarcinoma,lymphocytic leukemia

60mg/kgBW daily oral

Melphalan Multiple myeloma 150mcg/kgBW/day or 250mcg/kgBW daily 4 weeks oral

Chlorambucil Chronic lymphocyticleukemia, lymphoma

100mcg/kgBW daily oral

Carboplastin CNS neoplasm,GI carcinomas 300-360mg/m2 BSA by IV

Dacarbazine Lymphoma 2-4.5mg/kgBW for 10 days IV10-15mg/day for 4-8days oral

Busulfan Chronic myelogenous leukemia, polycythemia vera

60mcg/kg BW daily oral

Methotrexate Lymphoma, Sertoli cell tumor, osteosarcoma, metastatic TVT

10-15mg/day for 4-8 days oral

Fluorouracil GI, lung, liver, and mammary carcinomas (systemic); cutaneous carcinomas (topical)

15mg/kgBW once a week oral15mg/kgBW in 500ml DNS

Dactinomycin (Actinomycin D)

Choriocarcinoma, testicular carcinoma, rhabdomyosarcoma, lymphoma

15mcg/kgBW per day or400-600 mcg/m2 BSA IV

Doxorubicin Lymphoma, acute lymphocytic granulocyticleukemia, sarcomas carcinomas

60-75mg/ m2 BSA IV


134

Bleomycin Carcinomas (testicular, squamous cell –head,neck,seminoma,malignant teratoma

15,000IU thrice a week IM/IV

Vinblastine Lymphoma and leukemias, mastocytoma

0.1-0.5mg/kgBW IV

Vincristine TVTs, lymphoma and leukemias,CNS tumors, mammary carcinoma

25-75 mcg/kg or 1.4mg/m2

IV

Cisplatin Osteosarcoma, carcinomas (transitional cell, testicular, squamous cell of head and neck, ovarian, cervical, bladder

50-120mg/m2 BSA with % NS, IV

L-Asparaginase Acute lymphocytic and lymphoblastic leukemia and lymphoma

1000units/kg BW/10days with NSor Dextrose 5%

Hydroxyurea Polycythemia vera, mastocytoma, granulocytic and basophilic leukemia, thrombocythemia

20-30 mg/kgBW oral

Prednisolone Lymphoma, mast cell tumors, palliative treatment of brain tumors

60mg/m2 IM,IV

Tamoxifen Estrogen-receptor-positive mammary carcinomas

20mg/day single dose oral

Flutamide Testosterone-receptor-positive prostatic tumors; surgical castration preferred

250mg TID oral

*****


134

CHEMOTHERAPEUTIC MANAGEMENT OF PROTOZOAL AND RICKETTSIAL DISEASES

B.G. RAVINDRA

Protozoan and Rickettsial diseases are responsible for considerable mortality and morbidity in animals leading to devastating losses. Protozoan parasites are unicellular, eukaryotic organisms present in blood cells, tissues, skin and intestines. The Rickettsial organisms are minute, lack cytoplasm and are present in blood cells. Attempts to develop vaccines aginst these have been greatly handicapped due to complexity of different parasitic stages and their life cycle. Few vaccines are available against these diseases. Drugs currently available are effective, if they are used specifically with proper dose, route and course of treatment. Integrated method of control is very important by using vaccines, drugs and other managemental practices.

PROTOZOAL DISEASES

BABESIOSIS (PIROPLASMOSIS, RED WATER FEVER): The viable protozoa are present in blood stream of animals only in active stages of infection. Ticks (Boophilus spp.) are natural vectors in which transovarial transmission occurs.Contaminated needles and surgical instruments can physically transmit the infection.

Clinical signs: acute syndrome- high fever (up to 106oF), anorexia, depression, weakness, suspension of rumination, decrease in milk yield, increased heart and respiration rates. Conjuctiva brick red but soon changes to extreme pale due to severe anaemia. In terminal stages, severe jaundice, urine dark red/ brownish and produces stable froath. Many severely affected animals die after 24 hours and which survive febrile reaction last for week; pregnant animals often abort, course of disease is 3 weeks. In subacute infection- mild fever, hemoglobinuria absent .B. bigemina- cerebral babesiosis- incoordination, posterior paralysis, mania, convulsions and coma. High mortality inspite of treatment in cerebral form.B. divergens- additional sign is spasm of anal sphincter and feces expelled with greater force in long thin stream referred to as “pipe-stem feces”.Dogs: Signs vary from mild fever lasting for several days to sudden high fever, marked anemia, hemoglobinuria and jaundice.There may be cerebral form (hyperexcitability), alimentary form (stomatitis, gastritis, enteritis), respiratory form (dyspnea), circulatory form (edema), ocular form (keratitis, iritis) and muscular form (muscular weakness).


134

Therapy: a) Quinoronium sulphate derivatives- Acaprin (@ 1ml/50 Kg BW s/c, maximum dose 6ml otherwise salivation, panting, diarrhoea), Babesan, Piroparv, Piroplasmin. b) Acridine derivatives- Acriflavin (50-100ml i/v as 1% solution), Gonacrine, Trypan blue, Euflavine c) Aromatic diamidines- Diminazine aceturate (Berenil- 0.8-1.6 gm/100 Kg BW deep i/m), Stilbamidine, Propamidine, Phenamidine. d) Imidocarbs- Imizole @ 1mg/Kg BW s/c. (Imidocarb hydrochloride and Imidocarb dipropionate)

In horses- Berenil @ 11mg/Kg BW deep i/m.; Imidocarb- most favoured drug. B.equi- @ 4mg/Kg BW four IM injections of 10% solution at 72 hour interval. B.caballi- @ 2mg/Kg BW two injections at 24 hour interval. In donkeys- maximum @ 2mg/Kg BW.; Buparvaquone @ 4-6mg/Kg BW to control B.equi infection.In sheep- Berenil @ 3.5mg/Kg BW on two successive days or 12mg/Kg single dose. Supportive treatment- blood transfusion, Vitamin B complex.

Theilieroisis: Theileria parva, T. annulata- tropical theileriosis, T. mutans- less pathogenic, T. ovis, T. hirci- sheep and goat.T. camelensis- camel. Mainly transmitted by Hyalomma spp ticks; the organism pass trans-stadially through stages of larva, nymph and adult. No transovarian transmission.

Clinical signs: Initial sign- enlargement of superficial lymph nodes (prescapular, prefemoral, parotid) within 7-10 days of tick attachment. After 1-2 days, fever (105-106oF), depression, anorexia and decrease in milk yield. In later stages- nasal and ocular discharges, dyspnea, generalized lymph node enlargement and splenomegaly. In severe cases- emaciation, weakness and recumbency followed by death due to asphyxia. Ocassional cerebral theileriosis- circling, tremors, convulsions, profuse salivation and head pressing. T. annulata infection- additional signs of anemia and jaundice.

Treatment: a) Halofuginone lactate- coccidiostat but also has schizonticidal effect @ 1.2-2.0 mg/Kg orally for two days. Higher doses may be toxic- salivation, diarrhea, conjunctivitis, subnormal temperature and even death. b) Parvaquone @ 10 mg/Kg, may be repeated after 48 hours. c) Buparvaquone (Butalex) @ 2.5 mg/Kg i/m, may be repeated after 48 hours. d) Tetracyclines, Nivaquine act only on the piroplasm stages. e) Supportive treatment- blood transfusion, liver tonics, diuretics (to check pulmonary edema).

Trypanosomiasis (surra): Trypanosoma evansi- highly pathogenic, produce surra/ murrina/ mal de caders affect cattle, buffalo, sheep, goat, horse, camel and dogs. Horses and dogs most commonly affected, camel are carriers (chronic disease- Tibersa in camels-


134

3 year sickness). Transmission is through biting flies- Tabanus, Stomoxys, Lyperosia, Glossina, Hematopota even vampire bats help in transmission from one animal to other.Dogs may contract disease by eating infected meat (after 20 days of eating placenta of affected cattle).

Clinical signs: i) Peracute form- sudden death within 2-3 hours, animal dies showing some convulsions. Ii) Acute- Intermittant fever (103-105oF), animal dull and depressed, eyes are starring and wide open, breathing hard and noisy, staggering gait, circling movements, cattle stretches the rope to which it is tied, animal strikes head against wall or manger, stamping of feet, apparent blindness, frequent micturition, profuse salivation, muscular twitching followed by stage of comma and death within 6-12 hours. iii) Subacute/chronic- dullness, lacrimation, animal show progressive emaciation, rapid pulse, intermittent fever, edema of legs, wasting of muscles, loss of weight, occasionally diarrhea, some animal remain standing with neck extended even throughout the day. Dogs: may be acute form of disease, intermittent fever, anemia, edema and corneal opacity.

Camel: in chronic form and may last for 3 years, first sign is weakness of all quarters, eyes dull, alopecia, mucus membranes pale and show petechial hemorrhages, edema of legs, abortion common, mange is frequently seen in surra affected cases.

Treatment: a) Quinapyramine sulphate (Antrycide) curative @ 5mg/Kg BW; Quinapyramine sulphate and chloride (Antrycide prosalt); prophylactic @7.4 mg/Kg BW. In horses- give injection at 2-3 sites, in weak animals there may be salivation, restlessness and muscular tremors. b) Suramin @ 10mg/Kg BW i/v as 10% solution in horses and camels. c) Diminazine aceturate- against T.vivax and T.congolense @ 3.5-7.0 mg/Kg, toxic to horses and camels. d) Homidium- bromide and chloride salts @ 1mg/Kg BW. e) Isometamidium @ 0.25-1.0mg/Kg BW. f) Pyrithidium bromide @ 2mg/Kg BW.

Coccidiosis: Eimeria bovis and Eimeria zurnii are the common species, transmited by Feco-Oral route .Sub-clinical coccidiosis occur in 95% of the cases of ruminants. The other 5% are clinical cases.Anorexia, Diarrhoea (may or may not contain blood), dehydration, weakness, depression, weight loss, cachexia, Anaemia and death, Nervous coccidiosis-muscle tremors, staggering, convulsions and occasionally blind nes.

Amprolium @ 10 mg/Kg BW for five days, 1.25% crumble, 9.6%solution, 20% soluable powder ; Sulphaquinoxaline @ 8-70 mg/ kg BW for five days, as soluable powder or feed alternative; Monensin @ 1 mg/ kg daily for 30 days, as feed additive is effective.


134

Giardiosis: It is a chronic protozoal disease, common in dogs caused by Giardia canis and characterized by diarrhea, dysentery and abdominal pain. Treatment is with: Chloroquin or Metronidazole 250 mg/kg for 10 days are effective.

Balantidiosis: Balantidium coli exist as a commensal in the large intestine of pigs. Infection of cattle occurs by ingestion of the cysts. The organisms cause ulceration of the mucosa and diarrhea. Diagnosis is based on the detection of cysts/trophozoites in the faeces. Tetracyclines and Metronidazole are effective.

Toxoplasmosis: It is contagious disease of all species including man and is manifested by abortions and stillbirths in ewes and in all species characterized by encephalitis, pneumonia and neonatal mortality.

Clinical signs: cattle: in acute form marked by fever, dyspnoea, ataxia, hyperexcitability in early stages followed by extreme lethargy, stillborn or weak calves die soon after birth. The parasite plays no significant role in bovine abortion. Congenitally affected calves show fever, dyspnoea, sneezing, coughing, nasal discharge, clonic convulsions and grinding of teeth. The death may occur after 2-6 days.; Pigs: highly susceptible, all ages affected. Adults show debility, weakness, incoordination, coughing, tremors and diarrhea but no fever. In young pigs, high fever, diarrhoea, dyspnoea, coughing and ataxia. The pregnant sows abort and piglets are premature or stillborn; Sheep: abortion at last 4 week of gestation and neonatal death. is fever, dyspnoea and generalized tremors whereas lambs show fever and dyspnoea. Goats: abortion and stillbirths; Horses- mainly nervous signs including ataxia, circling movement, paresis, myeloencephalitis that may be positive factor for Wobbler syndrome.

Treatment: a) A combination of sulpha drugs @200 mg/Kg BW i/v for 3-5 days (sulphadiazine, sulphadimidine, sulphamerazine, sulphapyrazine) and pyrimethamine @ 1-2 mg/Kg BW orally is quite effective b) Sulfomoyl diamino diphenyl sulphon (SDDS) tried in pigs only @ 5 mg/Kg BW, not used clinically.c) Linomycin and Clindamycin are reported to be quite effective. D) Treatment of anemia as there is blood loss.

Bovine trichominiasis: It is a non-febrile protozoal disease of cattle leading to irregular estrus intervals, early fetal deaths and cases of pyometra.Trichomonas (Tritrichomonas) fetus, the etiological agent. Clinical signs: The parasite normally persists for 3 months in female genital tract after infection and a mild vaginitis is seen after the infective coitusThere is death of fetus within 2-4 months of conception leading to cases of repeat breeding and infertility.Abortions are usually not detected and main feature is failure of


134

animals to hold to service.In bulls, infection is confined to penile and prepucial surface and cause mild inflammatory response.

Treatment: a) The majority of infected cows recover and clear the infection within 3 months so not normally treated. In bulls- douches of prepuce and penis with acriflavin. Dimetridazole @ 50 mg/Kg/day orally for five days is quite affective. Ipronidazole can be administered IM but priorl, bulls should be treated with broad spectrum antibiotic to reduce preputial commensal bacteria which might inactivate the ipronidazole.

RICKETTSIAL DISEASES

Anaplasmosis (gall sickness) : A non-contagious disease of ruminants caused by obligate intraerythrocytic parasites: Anaplasma marginale, A. centrale, A. ovis. Mainly transmitted by ticks: Boophilus spp., Dermacentor spp, tabanid flies; infected hypodermic needles, blood transfusions

Clinical signs: Subacute (in younger ones): Temperature rises slowly up to 105oF- remain elevated or fluctuate, partial anorexia, animal may die at this stage or survive in an emaciated condition- mucous membranes become pale, urine may be brown but no haemoglobinuria. Peracute cases: sudden onset of high fever, anemia, jaundice, severe dyspnea and death within 24 hours; animals become hyperexcited and may attack pregnant animals may abort. Recovered bulls- testicular function depressed for several months. Sheep and Goat- usually subclinical infection but sometime severe anaemia in goats.

Treatment: a) Oxytetracycline @ 6-10 mg/Kg BW for three days or single injection of long acting oxytetracycline @ 20 mg/Kg BW i/m. b) Imidocarb @ 3 mg/Kg BW s/c. The problem of carriers can be avoided by using tetracycline @ 10-30 mg/Kg BW i/m daily for 10-15 days or 22 mg/Kg BW i/v daily for 5 days or long acting tetracycline @ 20 mg/Kg BW i/m weekly for 2-4 times or two injections of imidocarb @ 5 mg/Kg BW i/m or s/c. The oral use of chlortetracycline @ 11 mg/Kg BW for 30-60 days or 1.1 mg/Kg BW for 120 days also eliminates carrier animals. c) Supportive treatment- blood transfusion if PCV less than 15%.

Ehrlichiosis: Ehrlichia canis, Ehrlichia bovis are the etiological agents, commonly transmitted by ticks: Rhipicephalus sanguineus. Clinical signs: Anorexia, fever, incordination and enlargement of lymphnodes. The disease is of low significance in indigenous cattle, however it is serious problem in imported and newly introduced cattle. In dogs: Anorexia, fever, respiratory distress, Limb oedema, enlargement of lymphnodes,


134

bleeding tendacy (epistaxis, hematuria), and petichial haemorrhages on mucus membrane, Progressive weight loss and Neurological disorder may be seen.

Treatment: Doxcycline @ 5-10 mg/Kg BW per oral for about 10-14 days for four days ; Oxytetracycline @ 5-10 mg/Kg BW for four days ; Chloromphenicol, @ 5 mg/Kg BW for four days, Enrofloxacin @ 2.5-5 mg/Kg BW for four days may also be effective

*****


134

ANTIMICROBIAL THERAPY OF FUNGAL SKIN INFECTIONS

SANTOSH .P. SARANGAMATH

The ideal antifungal agent would be one that targets structures present in fungal pathogens that are absent in other eukaryotic cells. The fungal cell wall, a structure that is both unique and essential to fungi, would seem to be such a target. The vast majority of traditional antifungal drugs selectively target ergosterol, an essential component of the fungal cell membrane, with greater affinity than for cholesterol in the mammalian cell membrane. New antifungals have evolved especially azoles and triazoles, which selectively target fungal cell wall with least toxic effect on the body. Compounds that interfere with the synthesis of important fungal cell wall components such as glucan, chitin and mannoproteins have become a focus in the development of new antifungal agents.

Among the cutaneous diseases fungal diseases involving skin and appendages (Dermatophytosis) i.e cutaneous mycosis are commonly encountered as compared to the deep mycosis involving deeper organs of the body. Fungal infections involving the keratinized layers of the skin and its appendages like hoof, nails, and horns caused by group of mycelial keratinophilic fungi are called dermatophytes, The term dermatophytosis indicates the relationship of the disease with dermatophytes as etiological agents. Dermatophytes of dog and cats mainly belong to T. mentagrophytes, M. canis, M. gypseum.

The clinical signs of dermatophytosis are extremely variable; lesions are circular, irregular and vary from scaly patches of alopecia to inflammed to nodular erythematous patch of alopecia. Hairs partially broken/ fallen with bran like scales and crusts, signs like erythema, scales, crusts, thinning of hairs frequently in the form of broken hairs with secondary folliculitis with pruritus are usually observed.

Diagnosis is based on clinical signs, skin scraping examination, examination of hairs by wood’s lamp, and finally by fungal culture on saborauds dextrose agar or dermatophyte test medium. The gold standard for diagnosis is a fungal culture. Wood's light examinations are only screening tools, and direct hair examinations, although inexpensive, are only practical when infected hairs fluoresce on Wood's light examination. Finding these hairs allows rapidly diagnosing the infection and starting therapy. However, if the hairs are not present, this tool is time-consuming and not cost-effective in practice.


134

Another type of fungal or yeast disease is malassezia dermatitis; the clinical signs of which may be localized or generalized. Involving the external ear canal, interdigital skin, ventral neck, axillae, and inguinal region. Affected areas are erythematous, alopecic and often lichenified with or without hyperpigmentation. The lesions surface is often greasy and affected dogs have musty or malodour.

Diagnosis of malassezia dermatitis is by cytological examination or acetate tape impressions, stained with methylene blue which will be examined for the presence of round to oval monopolar budding yeasts.

ANTIFUNGAL THERAPY

Dermatophytosis will spontaneously resolve in most healthy cats, but treatment is recommended as the disease is zoonotic and highly contagious. The end point of therapy will go up to the achievement of mycological cure as well as decontaminated environment but not the clinical cure on the animal itself so as to prevent re-infection. A mycological cure is defined as two or three consecutive negative fungal culture results at weekly or biweekly intervals, and treatment should continue until all these negative culture results are obtained.Treatment recommendations:

1) Clipping the coat:. Clipping the coat removes infected hairs , minimizes continued shedding of hair fragments and spores; also makes topical therapy application easier and allows for more thorough penetration of topical antifungal agent. In addition, clipping helps shorten the duration of therapy and ultimately decreases the cost of treatment. It may temporarily worsen the infection by causing microtrauma to the skin. Also, it may result in environmental contamination if appropriate efforts to capture infected hairs and spores are not taken.Dipping is required in pets that live with children and elderly or immunosuppressed people, as well as in shorthaired breeds with generalized lesions and in longhaired cats regardless of lesion severity

2) Administering topical antifungal therapy twice weekly: The most effective topical antifungal agents are lime-sulfur, enilconazole, and miconazole. Lime-sulfur is suitable for sole therapy; combined topical and systemic therapy is the treatment of choice. It is important to note that fungicidal efficacy does not imply that one application of any of these products is 100% fungicidal. These products are fungicidal with repeated application. Lime-sulfur (8 oz/gal water ) has been used as the topical therapy of choice, and in some cases as the sole therapy. Enilconazole topical solution 10% concentrated solution (100 mg/ml) is effective against M. canis. It is associated with hypersalivation, anorexia, weight loss, emesis, idiopathic muscle weakness, and slightly elevated serum


134

alanine aminotransferase activity. Miconazole, as a sole therapeutic agent or in combination with chlorhexidine, the shampoo needing a contact time of 10 minutes for the therapeutic effect. This product can be irritating to the eyes and can cause skin irritation. Other dips like povidone-iodine, chlorhexidine have been consistently found to be ineffective against M. canis.

3) Administer systemic antifungal therapy - Systemic therapy is the treatment of choice for feline dermatophytosis. The efficacy of griseofulvin, itraconazole, terbinafine hydrochloride, and lufenuron alone or in combination with other therapies showed that griseofulvin, itraconazole and terbinafine are most effective agents Griseofulvin : is fungistatic that inhibits nucleic acid synthesis and cell mitosis metaphase by interfering with function of spindle microtubules.Its absorption is enhanced by administering it with fatty meal or by using formulations containing polyethylene glycol. It is teratogenic and should not be given to pregnant animals. also may interfere with spermatogenesis, so it is best avoided in breeding males. Anorexia, vomiting, and diarrhea are seen, which can be managed by dividing the dose into twice-daily administrations. Bone marrow suppression and neurologic side effects are most likely idiosyncratic reactions. Do not use griseofulvin in cats that have feline immunodeficiency virus (FIV) infections, because severe neutropenic reactions have been seen in cats with FIV.

The most commonly used dosing regimen is daily: griseofulvin microsize at a dosage of 25 to 50 mg/kg given orally once a day or divided twice a day; griseofulvin ultramicrosize at a dosage of 5 to 10 mg/kg given orally once a day or divided twice a day. Higher doses may be needed in refractory cases. Ketoconazole : is administered at the rate of 5 to 10 mg/kg b.wt. orally once daily for 21 days. Available in the form of tablets or shampoos, this will be useful for topical as well as systemic use. This drug is also tolerated in dogs, but long term therapy may involve the potential risk of causing liver as well as renal damage. Itraconazole : is a triazole derivative that alters fungal cell membrane permeability by inhibiting ergosterol synthesis; is fungistatic at low doses, fungicidal at higher doses.It is well-tolerated in cats and dogs, with vomiton, anorexia being most common adverse effects a) Daily dosing: 10 mg/kg orally once a day; b) Combined continuous/pulse therapy: 10 mg/kg given orally once day for 28 days and then on an alternate week regimen (one week off and one week on) . c) Short-term cycle therapy: 10 mg/kg given orally once a day for 15 days, followed by fungal cultures 10 -15 days later, this cycle is repeated until the cure. . It has replaced griseofulvin as the drug of choice for treating dermatophytosisTerbinafine : is the newest systemic antifungal agent to be used in treating dermatophytosis. It is an allylamine antifungal agent that suppresses the biosynthesis of


134

ergosterol by inhibiting the fungal enzyme squalene epoxidase.31 The drug is considered to be fungicidal against dermatophytes. Fluconazole : Fluconazole is also hepatotoxic and nephrotoxic, but its elimination from the stratum corneum is approximately 2 to 3 times slower than the plasma. Also, due to its rapidity in accumulation the skin after oral ingestion makes the drug to be administered once a week or daily for 2 to 4 weeks will help in improvement of the condition. This is administered safely at a dosage of 5 mg/kg/day which is well tolerated in both dogs and cats. Lufenuron : is a benzoylphenylurea drug that disrupts chitin synthesis and is used for flea control. Chitin is a critical component of the outer cell wall of fungi, and it is possible that drugs that disrupt chitin synthesis might also have antifungal activity. One report suggested it is useful in treating variety of fungal diseases including dermatophytosis. But still, lufenuron has been a widely debated topic in veterinary practice. 4) Considering Fungal vaccines: Intense interest in developing a fungal vaccine to prevent and possibly treat dermatophytosis continues. Fungal vaccines as sole therapy are not effective in treating dermatophytosis, but they may be a useful adjuvant therapy when combined with appropriate topical and systemic therapy and environmental control or a practical alternative to topical therapy in situations in which topical therapy cannot be used.

*****


134

NEWER ECTOPARASITICIDALS AND MISCELLANEOUS ANTIBACTERIALS

MEERA V.C.

Milbemycins

These are (eg:Moxidectin,Nemadectin,Milbemycin oxime,MilbemycinD) endecticidal macrocyclic lactones, similar to avermectins, active against all stages of nematodes including GI and lung nematodes,eye worms, schistosomes and ectoparasites- tick, flea. mite, horn flies, warbles,maggot fly bots.Wide safety index, (greater margin of safety in ivermectin sensitive collies) with no embryotoxic/teratogenic effects and safe for use in breeding and pregnant animals. But Abamectin and Moxidectin are contraindicated in calves and foals (< 4 month old). Dose:Moxidectin-200µg/kg,PO,IM;Pour on-500µg/kg, Milbemycin oxime-0.5-.99mg/kg-dog; 2mg/kg-cats); recently has been combined with lufenuron in a tablet formulation for the simultaneous prevention and control of flea infestations and nematodes

Insect growth regulators and insect development inhibitors :

These do not kill the target parasite directly, but interfere with growth and development. They act mainly on immature parasite stages and are not usually suitable for the rapid control of established adult parasite populations. Where parasites show a clear seasonal pattern, insect growth regulators can be applied prior to any anticipated challenge as a preventive measure. Lufenuron is administered PO to dogs (once monthly at a dose of 10mg/kg ) or cats ( 30mg/kg ) or by injection to cats. suppress the growth of adult fleas up to 32 daysCyromazine is effective against blowfly larvae on sheep and lambs and also against other Diptera such as houseflies and mosquitoes in poulktry sheds, commonly given a spremix in feed.

Methoprene (and Pyriproxyfen ) is used as a feed-through larvicide for hornfly ( Haematobia ) control on cattle. Fenoxycarb usually formulated in collar or spray with either pyrethroid (permethrin) or OPC (chloropyrifos) as an adulticide

Imidacloprid and nitenpyram are nicotinoids are modeled after natural nicotine. Imidacloprid is applied as a 10% spot-on topical product and is used primarily to control fleas on both dogs and cats. It also has excellent activity against lice. Nitenpyram is administered PO in pill form to kill fleas in both dogs and cats.


134

Fipronil a broad-spectrum acaricidal against fleas, ticks, mites, and lice.;effective against insects resistant or tolerant to pyrethroid, organophosphate and carbamate insecticides. Spinosad works as both contact poison and by ingestion to external parasites. It should not be used in puppies under age 14 weeks and in pregnant or nursing females. It is given once a month to kill fleas in dogs only, at a dose rate of 30-60mg/kg .Metaflumizone presented in combination with amitraz as spot on solution; dose is 20 mg/kg, equivalent to 0.133ml/kg bodyweight. It is contraindicated in puppies under 8 weeks of age., sick or debilitated dogs or dogs suffering from heat stress, pregnant and lactating animals.

MISCELLANEOUS ANTIBACTERIALS

Polymyxins: Colistin (Polymyxin E; available as sulphate for oral and topical use) and Polymyxin B.The spectrum is gram negative bactericidal. They are synergistic with sulfonamide and trimethoprim against variety of enterobacteriaceae. Colistin is synergistic with rifampin against multidrug resistant P.aeruginosa and is employed in coliform mastitis.They are indicted topically for Infections of skin, mucous membranes, eye and ear.

Bacitracin: Activity against gram-positive organisms , used topically alone or with neomycin or polymyxin for: infected eczema, infected dermal ulcers. and ophthalmic applications: suppurative conjunctivitis. infected corneal ulcer.Vancomycin: (and Teicoplanin) : The spectrum is gram positive bactericidal. Dogs-3 mg/kg PO, bid;10-20 mg/kg IV,tid. Ototoxicity, nephrotoxicity, and thrombophlebitis -adverse effects. Administration with aminoglcosides to be avoided.Indicated in MRSApneumonia, empyema, endocarditis, osteomyelitis and soft tissue abscesses and in severe Staph. infection

Fusidic acid (Sodium fusidate) : is bacteriostatic effective only on gram-positive bacteria such as Staph. and Corynebacterium. It is used topically for minor local skin infections, wounds. It should not be used with quinolones, with which they are antagonisticMethanamine (Hexamine) : a urinary antiseptic is bacteriostatic agent, becomes cidal in acidic urine. Active against both gram positive & negative organisms.Methamine mandalate – Dogs:10-20 mg/kg PO, bid.GI disturbances ,painful micturation, albinuria, hamaturia, cystitis, CNS symptoms produced occasionally. Use of urinary alkanizers: Na bicarbonate and Sulphonamides antagonise its action.Concurrent use of urinary acidifires such as ascorbic acid, methionine enhances its action.


http://en.wikipedia.org/wiki/Gram-positive

http://en.wikipedia.org/wiki/Corynebacterium

http://en.wikipedia.org/wiki/Staphylococcus

134

Tiamulin: gram positive bacteriostatic ,including Mycoplasma spp., Spirochaetes and obligate anaerobes. It is used for enteric pneumonia complex-Pigs-15 mg/kg IM, sid; for 3 days ; 8.8 mg/kg PO.sid. Overdose: transient salivation, vomiting and CNS depressions . It should not be administered to feeds in combination with ionophore antibiotics (monensin, lasalocid, salinomycin) as toxicity may occur.

Virginiamycin: broad spectrum, bactericidal against a wide range of organisms including staphylococci, streptococci and enterococci. It is commonly used as feed additive Overdose may result in gastric disturbances, dyspnea, emesis, tremor and ataxia.

Novobiocin: Spectrum mainly gram positive;.Dogs: 10 mg/kg q8h PO; Cattle:For treatment of mastitis in dry cows:. For treatment of mastitis in lactating cows-using the penicillin/novobiocin.

Quinupristin/dalfopristin: Streptogramins; Antibacterial spectrum:G+ve cocci .Given by IV infusion. Inhibitor of CPY3A4 enzyme-increased levels of certain drugs like diazpam, warfarin, protease inhibitors.

Linezolid: oxazolidinone derivative; gram+ve organisms:. Primarily bacteriostatic, except for Strep for which it is bactericidal. Active against mycobacterium tuberculosis. Indictaed in vancomycin-resistant infections and multidrugresistant gram +ve bacterial infections.

Mupirocin: gram positive bactericidal spectrum;used topically for staphylococcal and streptocococcal skin infections, wounds, burns etc.

Metronidazole : It is the the prototype of the group, Nitroimidazoles ( examples - tinidazole, secnidazole, ornidazole, satranidazole, nimorazole etc), has both antiprotozoal and antibacterial activity. Bactericidal against anaerobic bacteria, protozoas ; anti-inflammatory in bowel.

Indications : Various tissue protozoal diseases(amoebiasis, giardiaisis, trichomoniasis etc), in anaerobic and mixed bacterial infections : abdominal abscesses, pleuropneumonia,peritonitis, empyema, genital tract infections, , otitis media, stomatitis, osteomyelitis, soft tissue infections(topical) osteitis, arthritis, meningitis and sepsis. Dose: dogs : 44 mg/kg, PO, followed by 22 mg/kg, qid for anaerobic infections; 25 mg/kg, PO, bid for giardiasis; and 66 mg/kg, PO, sid for trichomoniasis. Courses of therapy are generally 5-7 days. Cats: 22-25 mg/kg, q 12h ; Cattle-75mg/kg,IV,q 12h for 3 doses. Tinidazole-15mg/kg,PO,q24h; Ronidazole- 30mg/kg,PO,q24h; Carnidazole- 20mg/kg,PO,q24h.


134

Contraindications: first trimester of pregnancy, young puppies, kittens, lactating animals

*****


134

CHEMOTHERAPEUTIC PROTOCOLS OF PARASITIC INFESTATIONS

PUTTALAKSHMAMMA

Chemicals/Drugs used to treat helminthic infections are called Anthelmintics; are classified in to antitrematodal, anticestodal and antinematodals. The Ideal drug should be active against all stages, least toxic to host, have wide therapeutic index, economical and environment friendly. The principle sites of drug action in parasite include neuromuscular system, biochemical reactions involved in energy metabolism and those related to reproduction.

A. Antitrematodal drugs: Drugs used against liver flukes, rumen flukes, lung flukes and Blood flukes

1. Carbon tetrachloride : Effective against mature Fasciola hepatica but not against Dicrocoelium dentriticum. Sheep – 3 ml P.o or S.c. Cattle 20 ml S.c. or 5 ml P.o. This drug is hepatotoxic. Hyperaesthesia, convulsions and coma may occur. More toxicity in hypocalcemic animals. In toxicity, give calcium compounds and reduce the protein intake.

2. Hexachlorethane: Effective against mature Fasciola sp Haemonchus sp and Trichostrongylus sp. The dose is 20 gm/100 kg. Monthly dosing in areas of repeated infestations.

3. Hexachlorphene : 10 mg/kg 4. Triclabendazole : Acting on both mature and immature liver flukes. Cattle –

12mg / kg, Sheep and goat 10 mg/kg.5. Nitroxynil : Active against mature and immature stages (4 to 6 wks) of Fasciola sp

and gape worms in birds. Reaction at the infection site is common. Induce yellow staining of the skin and wool. It is not used in lactating cows.

6. Rafaxanide : Effective against mature and immature flukes, oetsum ovis larva and Haemonchus contortus. 10 mg/kg P.o. Toxicity rare but not used lactating cows.

7. Oxyclozanide : 10 mg/kg. P.o. Safe for lactating, young and pregnant animals. Toxicity: Transient diarrhoea and hypogalactia. Others from this group for subacute and chronic fascioliasis are brotianide (22.5 mg+ thiophanate 200 mg/ml) closantel – 5 mg/kg I. M or 15 mg /kg. P.o. Effective against flukes, Haemonchus sp, larval flies & ticks.


134

8. Diamphenithide : 180 mg/ml susp. 100 mg/kg against mature and immature flukes

9. Bithiona : 50 mg/kg in divided doses on alternate days for 3 or 4 weeks is effective against paragonimiasis, fascioliasis and clonorchiasis, taeniosis and Diphyllobothrium latum

10. Chlorsulon : A sulphonamide 100 mg + Ivermectin 10 mg/ml inj. S.c. Good for biliary fascioliasis in lactating cattle

11. Resorantel : 65 mg/kg P.o. in cattle and sheep against only intestinal paramphistomes.

12. Albendazole : 7.5 mg/kg in cattle, sheep and goat, for the control of Fasciola sp 15 mg/kg b.wt for the treatment of Dicrocoelium dentriticum in sheep.

13. Lithium Antimony thiomalate 6%. Cattle 15-20 ml i.m 2-3 doses at weekly intervals against nasal schistosomiosis.

14. Praziquantel : used in human schistosomiosis, clonorchis sinsensis and opisthorchis viveroni.

B. Anticestodals

1. Natural compounds : The earliest anticestodal drugs used were of plant origin, like minced pumpkin seeds, powdered rhyzome of male fern, kamala and Arecholine

2. Inorganic Compounds : a) Tin compounds were used against human, dog and poultry tapeworms. Stannous chloride – man, dog-0.5 gm daily for 8 days. b) Di-n-butyl tin dilaurate : 1ml for poultry c) Lead arsenate : used for treating Moneizia in lambs and calves.

3. Synthetic organic compounds : i). Hexachlorophene : 100 mg tab

ii). Bunamidine hydrochloride : Used against Echinococcus granulosus : second dose after 6 weeks to eliminates those which were immature, Also, effective against Dipylidium caninum and moniezia expansa.

iii) Dichlorophen : Dogs : 300 mg/kg ,Cats : 100-200 mg/kg

iv) Niclosamide : Dogs & cats: 100-157 mg/kg ,Cattle : 50 mg/kg ,Sheep, Goat, rabbit and monkey : 100 mg/kg

v). Paramomycin Sulphate :

vi) Praziquantel : 2.5 to 7.5 mg/kg P.o or S.c against Diphyllobothrium latum, Hymenolepis nana, Taenia saginata etc. Dipylidium caninum, Taenia sp, E. granulosus


134

Spirometra, Side effects: Malaise, dizziness, headache, abdominal discomfort with or without nausea. Not used in puppies or kittens younger than 4 wks.

vii). Nitroscanate : 50 mg/kg used against Dipyllidium caninum, Taenia

viii) Benzimidazoles : a) Mebendazole b) Albendazole c) Fenbendazole d) Oxfendazoel e) Febantel etc are effective against tapeworms.

C. Antinematodals

1. Phenothiazine : 10 gm/45kg used in strongyles, Triodontophorus, Haemonchus, Ostertagia and Trichonema. On exposure to light, it causes photosensitization keratitis manifested by ulceration of the cornea. So, avoid sun for 2-3 days.

(a) Piperazine : 75 mg/kg P.o. for mammals ,3g/bird in water for 3d in poultry

(b) Bephenium hydroxynaphthoate : irritant and poor absorption from the gut. 80%. Cure of Trichostrongylus in man, Ancylostoma in man and dogs and nematodirus in ruminants.

(c). n-Butyl chloride : 90% effective against ascarids and 60% against hookworms.

(d) Toluene : 0.2 ml/kg P.o. 98% effective in ascarids and hookworms in dogs and cats, Emesis, tremors and ataxia in pups and kitten.

(e) Tetrachloroethylene : Removes 90% hookworms. To prevent toxicity give fat free diet 48h before dosing. It is hepatotoxic, causes dizziness, inco-ordination and death. Contraindicated in tapeworm infection as the tapeworms may ball up due to irritation and occlude the intestinal passage.

(f) Methyridine : 200 mg/kg P.o., S.c, or I.P. Twice the normal dose is toxic. Diethylcarbamazine potentiates toxicity.

(g) Diethyl Carbamazine citrate: 6 mg/kg P.o or S.c in dogs in Spirocerca lupi, human wucheria bancrofti or Loa loa, onchocerca volvulus, cutaneous larva migrans and tropical eosinophilia. 22 mg/kg i.m for 3 days in early cases of Dictyocaulus viviparous infection in cattle, 5mg/kg daily or alternate day commencing before exposure and continuing 60 days after exposure.

(h) Disophenol : 10 mg/kg P.o., S.c. or i.m. Effective against hookworms and spirocerca lupi of dogs, syngamus trachea in turkeys. It causes pyrexia, tachycardia, polypnoea,


134

corneal and lens opacity in dogs which regress within 7 days. Non blood sucking and histotropic parasites are unaffected, orally administered drug is more toxic.

(i) Phtholofyne : 200 mg/kg for whip worm. 24hour fast followed by light meal after dosing. Toxicity leads to emesis, ataxia, and death.

(j) Hygromycin-B : An antibiotic in feed for swine and poultry against ascarids, capillaria, oesophagostomum and Heterakis gallinarum. Feed 6 weeks prior to farrowing in swine.

3. Tertrahydropyrimidines : Less active against larval stages and have minimal action on hypobiotic larvae. Not ovicidal.

a) Morantel citrate : Not effective against adult lung worms. 10 mg/kg P.o in cattle & sheep

b) Pyrantel pamoate : used for round worms in horses, dog and man. Due to mutual antagonism, piperazine and pyrantel compounds should not be combined.

c) Oxantel : Specific single dose treatment of Trichuriasis in dog at 55 mg/kg.4. Benzimidazoles :Benzimidazoles have a high therapeutic index, but not to be used in the first month of pregnancy (teratogenic).

a) Thiabendazole : Not widely used now b) Mebendazole : Generally not used in cattle, sheep and horse 10 mg/kg. 25-50

mg/kg twice daily for 5 days for round worms and tapeworms in dogs.c) Parbendazole : 30 mg/kg P.od) Albendazole : It is used in the treatment of roundworms, tapeworms and flukes. 5

mg/kg for roundworms and 7.5 mg/kg for flukes in sheep and goats .7.5 mg/kg for round worms and 10 mg/kg for flukes in cattle. 5 mg/kg in horses

e) Fenbendazole : In addition to important roundworms, it is effective against hypobiotic larva and also on tapeworms in sheep, Goat and dogs.

f) Oxfendazole : Active against round worms, their inhibited larva and tapeworms 4.5 mg/kg P.o as a single dose to cattle, sheep and pig. 10mg/kg daily for 3 days in horses and dogs

g) Oxibendazole : Effective against roundworms and lung worms in horses 10 mg/kg P.o.

h) Flubendazole : 5 mg/kg P.o. mainly used in pigs against round worms i) Luxabendazole : Effective against round worms and flukes .7.5 mg/kg for round

worms


134

5. Benzimidazole pro-drugs.These are converted in vivo to benzimidazoles. The drugs are ovicidal, larvicidal and affect adults including some tape worms (Taenia sp)

a) Febantel : Converted to fenbendazole and oxfendazole, 7.5 mg/kg in cattle and 5 mg/kg in sheep

b) Thiophanate : Converted to lobendazole 50 mg/kg c) Netobin : Converted to albendazole 7.5 mg/kg P.o in cattle & sheep

6. Imidazothiazoles :

a) di-Tetramisole b) Levamisole (1-Tertramisole) : Effective against larvae (but not hypobiotic and not ovicidal) and adults. anthelmithic dose is immunostimulant. The drug is non-teratogenic and hence can be used in pregnant animals. The dose is 7.5 mg/kg Antidote is Atropine

7. Macrolides (macrocyclic lactones)

a) Ivermectin : 0.2mg/kg single oral or P.o.Effective against nematodes and ectoparasites. Used at 6 ug/kg at one month intervals for prevention of Dirofilaria immitis infestation in dogs. Other macrolides includes Doramectin, milbomycin-D, milbomycin oxime, Eprinomectin, Moxidectin and selamectin.

8. Organophosphorus compounds : The use is restricted to the treatment of round worms of dogs, cats, pigs and especially horses where they also control the stomach bots.

a) Dichlorovos : 20 -40 mg/kg in horses ,30-40 mg/kg in pigs,27-33 mg/kg in Dogs. They may be incorporated into polyvinyl chloride resin pellets for slow release and safety

b) Coumaphos : 2 mg/kg/day for 6 days in feed c) Trichlorofon : A prodrug of dichlorvos used in horses at 40 mg/kgd) Napthalofos : Narrow margin of safetye) Crufomate: used for warble fly control.

Broad Spectrum Combinations

1. Clorsulon and Ivermectin : For use in cattle 1 ml/50 kg. S.C.2. Dichlorophene and Toluene: used in dogs against cestodes and nematodes 3. Diethylcarbamazine and oxibendazole : used in dogs for prevention of infection

with D. immitis and A. caninum, and for the removal of T. canis and T.vulpis


134

4. Febantel, praziquantel, and pyrautel: A single dose is given to dogs to remove D. caninum, T. pisiformis, E.granulosus, A. caninum, U. stenocephala, T. canis, T. vulpis

5. Milbemycin oxime and Lufenuron :This is given once every mouth to remove G I worms and control of flea population

6. Praziquantel and pyrantel : A single dose is given to cats and kittens to remove D. caninum, Taenia sp Ancylostoma sp and T. cati

7. Ivermectin and pyrantel pamoate : This is given orally to dogs every 30 days to prevent D. immitis and for the treatment & control of T. canis, T. leonina,

*****


134

CHEMOTHERAPEUTIC PROTOCOLS OF IMPORTANT ZOONOTIC DISEASES PRADEEPKUMAR

The antimicrobial therapy of important diseases of zoonotic importance are discussed in brief in this article.

Anthrax:Penicillin, the drug of choice for years other drugs from penicillin family such as amoxicillin should be equally effective. Doxycycline, one of the tetracyclines, most recently listed as the drug of choice in treating anthrax. Ciprofloxacin, one of the quinolone antibiotics and is also effective. is recommended as the first drug to use until the sensitivities of the organisms are known Lung infections may be treated with IV antibiotics.If untreated, cutaneous anthrax may result in death. Untreated inhalation anthrax always results in death.

Brucellosis: Use of surgical hand gloves is recommended during vaccination and yhe vaccine should be handled properly. Vials, syringes, needles and gloves used during vaccination should be discarded by suitably disinfecting them.Streptomycin is the drug of choice. Doxycycline (per oral dosage) is also effective. Flouroquinolones can also be used.

Tuberculosis: Tuberculosis is curable only with a combination of chemotherapy, in which a medley of three or four anti-tubercular drugs is administered. The first line drugs are Isoniazid, Rifampicin, Ethambutal, Pyrizinamite, and Streptomycin. The treatment is streamlined over a period of 6-9 months.Azithromycin, clarithromycin, ciprofloxacin are the second line agents, used in cases of resistance and toxicity tio first line drugs.

Toxoplasmosis: From acute maternal infection during pregnancy; incidence/severity related to trimester of infection; may cause abortion, stillbirth, and premature birth. Manifestations varied: if not evident at birth, usually develop in later life (85%) and may include: microcephaly, hydrocephaly, neurologic disease/mental retardation, ocular disease, pneumonitis, hepatomegaly, splenomegaly, icterus, anemia, thrombocytopenia. Clindamycin; sulfa trimethoprim; monitor for evidence of bone marrow suppression. Do not feed raw or undercooked meat to cats, keep cats inside and do not let them hunt.

Plague (bubonic, pneumonic, and septicemic): The etiological agent is: Yersinia pestis (gram-negative coccobacillus); Rodents (dog, ground squirrel, rock squirrel) are the major reservoirs. Bubonic form (most common; 80 - 90% of cases): enlarged, painful


134

lymph nodes (axillary, cervical, inguinal), fever, chills, weakness, GI signs, headache, myalgia. Septicemic: septic shock, meningitis, coma, .Pneumonic (least common: severe pneumonia, fever, dyspnea, and hemoptysis). Aminoglycosides, fluoroquinolones, are effective agents with supportive care.Insect repellent, appropriate clothing, flea control for pets and environment, rodent control. Avoid contact of cats with reservoir hosts.

Ringworm: Patchy pruritic dermatitis that may be multifocal. Many possible etiologies in people (zoophilic, geophilic, anthrophilic dermatophytes); M. canis most common zoophilic dermatophyte and infections are from cats. Keeping the affected part of the body dry and clean and antifungal agents like griseofulvin, terbinafine, miconazole, ketoconazole are used.

Cryptosporidiosis : Cattle, rodents, dogs, cats, birds, raccoons are the reservoirs. Immunocompetent ones: Self-limited acute watery diarrhea, epigastric pain, nausea, anorexia requiring fluid therapy. Immunocompromised: chronic profuse watery diarrhea, fever, epigastric pain, nausea, anorexia. Gall bladder infection possible. Respiratory tract infection may occur. Azithromycin may be effective. Evaluate for concurrent immunosuppressive conditions if prolonged treatment needed. Clean and disinfect environment (100% ethanol or 50% bleach with 30 minutes of contact effective after removal of organic matter)

Q-fever : Coxiella burnetii is the etiological agent. Cattle, sheep, and goats are the primary reservoirs. Inhalation of organisms from air that contains airborne barnyard dust contaminated by dried placental material, birth fluids, and excreta of infected herd animals. Outbreaks occur mainly from occupational exposure involving veterinarians, meat processing plant workers, sheep and dairy workers, livestock farmers, and researchers at facilities housing sheep. Acute: high fever (up to 104-105° F), severe headache, general malaise, malign, confusion, sore throat, chills, sweats, non-productive cough, nausea, vomiting, diarrhea, abdominal pain, hepatitis and chest pain. 1-2% mortality in humans. Chronic: Endocarditis, generally involving the aortic heart valves, less ommonly the mitral valve. Patients who recover can develop lifelong immunity. Incubation period: 2-3 weeks. Doxycycline is the treatment of choice for acute Q fever. Antibiotic treatment is most effective when initiated within the first 3 days of illness. A dose of 100 mg of doxycycline taken orally twice daily for 15-21 days is a frequently prescribed therapy. Quinolone antibiotics have demonstrated good in vitro activity against C. burnetii and may be considered.


134

Influenza : Two antiviral agents: zanamivir (TN: Relenza) and oseltamivir (TN: Tamiflu) are used to prevent or reduce influenza A and B symptoms. These should not be used indiscriminately, because viral resistance to them can and has occurred. Also, they are not recommended if the flu symptoms already have been present for 48 hours or more. Severe infections in some patients may require additional supportive measures such as ventilation support and treatment of other infections like pneumonia that can occur in patients with a severe flu infection. General precautions to prevent zoonotic infections: Hand hygiene: Consistent thorough hand hand washing with plain (nonantimicrobial) soap and running water mechanically removes organic material and reduces the number of transient organisms on the skin, whereas antimicrobial soap kills or inhibits growth of transient and resident flora.To reduce the opportunity for cross-contamination, liquid or foam soap products should be selected rather than bar soaps. Hands should be washed between animal contacts and after contact with feces, blood, body fluids, and exudates. Alcohol-based hand rubs are highly effective against bacteria and enveloped viruses and may be used if hands are not visibly soiled. Use of gloves and sleeves: reduce the risk of pathogen transmission by providing barrier protection; though, wearing gloves is not a substitute for hand washing. Gloves are available in a variety of materials. Choice of gloves depends on their intended use. If allergic reactions to latex are a concern, acceptable alternatives include nitrile or vinyl gloves.Facial protection: prevents exposure of mucous membranes of eyes, nose, and mouth to infectious materials. Whenever exposures to splashes or sprays are likely to occur, such as those generated during lancing of abscesses, flushing wounds, dentistry, suctioning, lavage, and necropsy, facial protection- surgical mask worn with goggles or a face shield is used.. Respiratory tract protection: designed to protect the airways of the wearer from infectious agents that are transmitted via inhalation of small particles.It may be appropriate in certain situations, such as during investigations of abortion storms in small ruminants (Q fever), high mortality rates among poultry (avian influenza),positive herd (bovine tuberculosis), and avian chlamydiosis. Disposable particulate respirators often resemble surgical or dust masks but fit closely to the wearer’s face and are designed to filter smaller particles (surgical masks are not designed to prevent inhalation of small particles). Protective outerwear: a. Nonsterile gowns: Gowns provide better barrier protection than laboratory coats. Permeable gowns- used for general care of animals in isolation. Impermeable gowns should be used when splashes or large quantities of body fluids are present or anticipated.. b. Footwear: Footwear should be suitable for the specific working


http://www.medicinenet.com/script/main/art.asp?articlekey=11941

http://www.medicinenet.com/script/main/art.asp?articlekey=11942

134

conditions (eg, rubber boots for farm work) and should protect personnel from exposure to infectious material as well as from trauma. Recommendations include shoes or boots with thick soles and closed-toe construction that are impermeable to liquid and easy to clean.. d. Head covers: Disposable head covers provide a barrier when gross contamination of the hair and scalp is expected.

*****


134

STEROIDS AND ANTIHISTAMINICS OF VETERINARY CLINICAL IMPORTANCE - AN OVERVIEW

U.SUNILCHANDRA

The class of steroids include sex steroids, corticosteroids (glucocorticoids) and anabolic steroids. The clinical pharmacological aspects of glucocorticoids, anabolic steroids and antihistaminics of veterinary relevance have been outlined in this article. Glucocorticoids (GC) potentially affect every cell in the body and produce a wide spectrum of effects depending on tissue concentration and cell type. Classification: 1. Short acting (duration of action < 12 hours) eg: cortisone, hydrocortisone (1 *) 2. Intermediate acting (duration of action: 12–36hours) eg: prednisone(4*),prednisolone(4*), methylprednisolone(5*), isoflupredone(50*) and triamcinolone(5 *) 3.Long acting (duration of action > 48hours)eg: dexamethasone (30*), betamethasone (30*),, paramethasone (120*), and flumethasone (120*) * Antiinflammatory potency as determined by comparison to a cortisol a value of 1.0.Injectable glucocorticoids: To treat shock, doses of GC are 50 to 100 times the physiological level.; phosphate and succinate esters are used IV. .To suppress the immune system, doses are about 20 times the physiological level; solutions of free steroid alcohols administered IVor IM; Egs include: Dexamethasone, FlumethasoneTo inhibit inflammation, doses are 10 times the physiological levels.Preparations are acetate and acetonide esters; given IM,SC or intra-articular (into the joint).Egs of long-acting formulations include:methylprednisolone acetate, triamcinolone acetonide, isoflupredone acetate, betamethasone dipropionate. Isoflupredone acetate is 14 and 4 time times more potent than hydrocortisone and prednisolone respectively as anti-inflammatory. Topical corticosteroids: the potencywise classification:Mild: e.g. hydrocortisone prednisolone, dexamethasone ; Moderate: e.g. betamethasone valerate triamcinolone acetonide fluocinolone acetonoide.;Potent: e.g. betamethasone dipropionate betamethasone valerate, diflorasone diacetate;Very potent: e.g. clobetasol propionate, halobetasol propionate,, betamethasone Topical agents alone or in combination with antibiotics are used to treat chronic superficial keratitis, conjunctivitis or minor cuts, scratches, hot spots, or inflammation due to contact dermatitis, allergies, ear infections or inflammations Clinical Indications of GCs: 1.Adrenocortical insufficiency (acute,chronic): (Addison’s disease).A rapidly acting parenteral corticosteroid with the most mineralocorticoid effect administered in conjunction with vascular volume expander-isotonic saline.


134

Relativemineralocorticoidpotency:hydrocortisone>prednisolone/prednisone>methylprednisolone > dexamethasone 2.Allergic disorders: Dexamethasone , methylprednisolone acetate, prednisolone sodium succinate, triamcinolone acetonide injectables are indicated in the treatment of allergic conditions such as bee stings, drug allergy, pruritic dermattose,allergic lung (rhinitis, astma). In acute case of atopic/flea allergy dermatitis the lowest dose necessary or, if possible, alternate day therapy with either prednisolone, methylprednisolone, or triamcinolone is instituted.. 3. Ocular and Aural Inflammtion(otitis externa) : Topical steroids -for conditions of the anterior chamber; systemic steroids for posterior chamber. Contraindicated in viral infections, fulminant bacterial infections, fungal infections, injuries (ulcers) and glaucoma. 4.Musculoskeletal Inflammation,: osteoarthritis, bursitis, tendonitis, immune mediated rheumatoid arthritis, myositis; used in conjunction with therapies that target the underlying cause 5. Adjunct therapy of cardiogenic and hemorrhagic shock: The primary treatment is the administration of large volumes of crystalloid solutions.Dexamethasone sodium phosphate and prednisolone sodium succinate are recommended. The primary treatment of septic shock (endotoxaemia) is antimicrobial therapy and supportive parenteral fluid therapy 6. As immunosuppressive in immune mediated haematopoietic and skin diseases: immune-mediated:hemolytic anemia,thrombocytopenia,neutropenia(Dexamethasone, prednisolone, and prednisone) skin diseases like Systemic lupus erythematus, pemphigus complexus and myasthenia gravis.7.Respiratory conditions: in acute respiratory distress syndrome in cattle, chronic obstructive pulmonary disease in horses, feline asthma syndrome, aspiration pneumonia, pulmonary oedema from drowning, inhalation injury etc 8. Malignancies/Neoplasia: As a component of most combination regimens for malignancies, in acute lymphocytic leukaemias, CNS tumors, lymphosarcoma, mast cell tumor, multiple myeloma. 9. Termination of pregnancy/ Induction of abortion: Dexamethasone injection ,after the 100th to 150th day of gestation, in conjuction with prostaglandins. Mummification, retained placentas, metritis or dystocia are the possible complications 10.Induction of Parturition : Dexamethasone,betamethasone and flumethasone have been used; generally in conjunction with a prostaglandin.Parturition may be induced in the last few weeks of gestation involves much less risk to the fetus than earlier termination of pregnancy. 11. Cerebral oedema/ Hydrocepahlus due to CNS neoplasms/parasites, sarcoidosis, spinal cord injury due to acute trauma: Methylprednisolone sodium succinate administered 12.Intervertebral disc diseas.:Dexamethasone, within 8 hours of an acute spinalcord injury. flumethasone,Methylprednisolone,prednisolone, administered at an anti-inflammatory dosage, are indicated as supportive therapy in intervertebral disk disease (Hansen type:1).13.Ketosis in Cattle: Dexamethasone,flumethasone,isoflupredone acetate and prednisolone acetate injectable suspension - more effective when administered with IV


134

glucose solutions. .A significant decrease in milk production is expected in lactating cattle. 14. Mastitis: Dexamethasone is used as adjunctive therapy in the treatment of selected cases of acute coliform mastitis to relieve some of the systemic signs (due to endotoxin) and mammary gland inflammation; administered in conjunction with IV fluids and antimicrobialsSide effects : of GC are mainly due to two types: from abrupt withdrawal or after chronic therapeutic use of high doses. The longterm use of supraphysiologic doses. may lead to iatrogenic Cushing’s syndrome, characterized by polyuria, polydipsia, bilaterally symmetric alopecia, increased susceptibility to infection, peripheral myopathy and muscle atrophy, and redistribution of body fat. Longterm suppression of HPAA may cause adrenal gland atrophy and resultant iatrogenic secondary hypoadrenocorticism (acute adrenal insufficiency/ Addisons disease).-lethargy, weakness, vomiting, and diarrhea particularly in dogs and horses. Other adverse effects: flare up of underlying diseses, fluid and electrolyte disturbances (potassium loss, sodium retention, and fluid retention), inhibition of bone growth, collagen synthesis ,decreased growth rate, delayed wound healing, gastrointestinal irritation/ulceration/perforation. hematopoietic changes;weight gain or weight loss, precipitation of diabetes mellitus, increased susceptibility to infections,immune response suppression,osteoporosis, myopathy, cataracts etc. Contraindications: Infectious diseases,GIT/ peptic and corneal ulcers, diabtes mellitus, demodicosis, osteoporosis, epilepsy, CHF, renal failure, late pregnancy, recent major surgery , hypertension, ulcerative colitis and pancreatitis Principles of GC therapy1. Administered at the lowest dose known to be effective or the smallest dose that

achieves the desired effect. Drugs with primarily GC activity and minimal dose to achieve the desired effect is chosen. Topical or local therapy is preferred whenever possible. Once-daily dosing is usually preferred Large steroid doses are administered in divided doses to reduce local GIT effects.

2. Animal should not have been vaccinated several weeks before/ after GC therapy. In order to mimic the normaldiurnal cycle and reduce the risk of adrenal suppression, GC should be given in morning between 6–10AM

3. Alternate day therapy: every other day treatments are used to maintain remission without side effects of daily or twice daily administration such as HPAA suppression.

4. Pulse therapy: parenteral administration of supra pharmacological doses of short acting steroids for shorter periods of time

5. Short term therapy: ( <2weeks) : short acting steroids, administered in divided doses ,bid, till the condition is controlled (4-7days) and discontinuing therapy once the condition is controlled


134

6. Long term therapy: Starting as above for 2 weeks, then bringing the dosage to the lowest possible single dose per day or doubling the dose and give every other day. Giving adjunctive therapy like antihistaminics,to keep steroid dose as low as possible. Tapering the dose and gradually withdrawing before stopping therapy in order to avoid iatrogenic hypoadrenocortisism.

Dosages: Hydrocortisone: adrencocortical insufficiency- dogs: 0.5mg/kg.PO.bid; adjunctive therapy of shock- dogs and cats: 50mg/kg,IVq3-6h;antiinflammtory activity-dogs and cats: 5mg/kg,PO,bid, IV,IM(sid); adjunctive in photosensitization-cats: 100-600mg(total) in 1 L 10% dextrose saline,IV. Isoflupredone acetate: cattle-10-20mg total dose, q24h, IM; Pig-0.036mg./kg/day,IM; dog-0.125-0.25mg/kg/day,IMCortisone: Dogs and cats: 1mg/kg.PO,IM,sid.Prednisolone: chronic/subacute adrencocortical insufficiency- dogs: 0.2-0.4mg/kg.PO.sid;acute adrencocortical insufficiency- dogs: 4-20mg/kg.IVq6h; adjunctive therapy of shock- dogs and cats: 5-10mg/kg,IVq3-6h; for antiinflammtory activity-dogs and cats: 0.5-2mg/kg,PO,sid,IM; dermatological /immune mediated disorders- dogs: 1-2mg/kg,PO,bid for 7-10 days,-cats: 2-4mg/kg,PO, q48h 100-600mg(total) in 1 iL 10% dextrose saline,IV. Methyl prednisolone: anti inflammtory action -dogs and cats: 0.25-1mg/kg,PO; Methyl prednisolone acetate(depot preparation)-dogs: 1mg/kg,SC,IM,cats-2-5mg/kg,SC,IM for CNS trauma, spinal cord injury: dogs: 30mg/kgIV Triamcinolone:dogs,cats:0.11-0.22mg/kg,PO,sid;cattle:0.02-0.04mg/kg,IM;horse-0.1-0.2mg/kg,IM Dexamethasone: adjunctive therapy in shock-dogsand cats:4-6mg/kg,IVq3-6h; antiinflammtory -dogs and cats: 0.05-0.125mg/kg,PO,sid,IM; cattle- 0.06-0.1mg/kg,IM.sid; swine-1-10mg(total) IM,IV;induction of parturition- cattle: 20-30mg(total),IM single dose; sheep-8-16mg(total); termination of pregnancy- cattle: 25mg(total),IM,slow IV, bovine ketosis: 5-20mg(total)Betamethasone: antiinflammtory acion-dogs and cats: 0.025mg/kg,PO,sid, all species-0.04-0.08mg/kg,IM,IV; for induction of parturition- cattle: 20-30mg(total),IM single dose; for bovine ketosis: 0.04-0.08mg/ kg,IM,IVANABOLIC STEROIDSAnabolic (androgenic )steroids are synthetically produced variants of the naturally occurring male hormone testosterone. The anabolic effects of the drugs promote the growth of skeletal muscle, and the androgenic effects promote the development of male sexual characteristics, which is responsible for the majority of the side effects of steroid use. Nandrolone and Stanozolol are two agents commonly used in animals.Clinical Indications: 1) Convalescence: Following surgical operations and febrile diseases; .Debilitating, wasting diseases, catabolic states, in major acute illness, immunosuppressive state sand diseases, severe trauma, -conditions where there is negative nitrogen balance


134

2) Bone metabolism conditions – osteoporosis in elderly, to remove tissue depleting processes in young ones , in diseases like CD, heavy parasitism, hypoproteinaemia etc. 3) To hasten the tissue repair (tendon, bone damage) after major surgery and to promote the healing and reunion in fracterous conditions. 4) To counteract glucocorticoid induced catabolism and negative effects 5) To stimulate erythropoiesis in conditions of hypolplastic, hemolytic anemia and malignancy conditions 6) Testosterone deficiency conditions – male hypogonadism, andropause Nandrolone decanoate (laurate): Dose : 1 mg/kg bodyweight,IM,SC at three week intervals, monthly up to 50 mg (Dogs); 25mg (cat); 200mg(horse). Stanozolol : has appetite stimulant action especially in cats. Dose: 0.25-3 mg/kg, PO, SID; 2-10 mg/kg, IM, once weekly Contraindications: Pregnancy, prostate or breast carcinoma in male.They may improve glucose tolerance and decrease the need for insulin or other antidiabetic medicines in diabetics. Side Effects: Hypertension, acne, fluid retention, gynaecomastia, increased aggression, epistaxis, withdrawal depression, reduced sperm count,prostate enlargement,sterility(long term), reproductive failure, suppressive effect on sexual development in young male animals, libido reduction, appetite stimulation, benign prostate enlargement acne and hair loss; In female: Masculinisation of a female foetus, growth of facial hair, male-pattern baldness, changes in or cessation of the menstrual cycle, enlargement of the clitoris, deepened voice

ANTIHISTAMINES

Antihistamines are a) H1-receptor antagonists: that provide symptomatic relief of allergic signs caused by histamine release, including pruritus and anaphylactic reactions and b) H2 -receptor antagonists that mainly control overproduction of gastric parietal cell mediated acid secretion.

H1-RECEPTOR ANTAGONISTS

Conventional antihistaminics, are categorized as First generation (Sedative,withanticholinergiceffects:Eg:clemastine,dimenhydrinate,diphenhydramine,doxylamine,pheneramine,chlorpheneramine,pyrilamine,tripelennamine,cyproheptadine,promethazine,alimemazine,hydroxyzine,bromopheniramine and the behavior-modifying tricyclic antidepressants: amitriptyline,clomipramine, doxepin) and Second generation (Nonsedative,with non anticholinergic, lesser antiprutitic action; Eg:oxatomide terfenadine, azatadine cetirizine, loratadine, astemizole) antihistamines.


134

Clinical Applications and Interactions : Responses to antihistamines vary considerably, and several may need to be tried to find one that is effective for an animal As adjunct therapy for the management of systemic anaphylaxis ( allergens, insect

stings, drug induced), to control ongoing mediator release following the acute therapy of circulatory collapse . with adrenaline and fluids.

In the management of pruritus, generally given in conjunction with glucocorticoid, and when pruritus is controlled (generally within 5 days) the glucocorticoid is withdrawn and antihistamine therapy maintained to prevent recurrence of pruritus.

Act synergistically with NSAID, glucocorticoids and ω-6/ω-3 (omega-6/3) fatty acid supplements and may allow dosages of these agents to be reduced in some cases

Used in acute septic gangrenous mastitis, septic metritis, retained placenta, myoglobinuria, ruminal atony conditions in ruminanants.

Some ( eg: promethazine,meclizine,cyclizine, diphenhydramine) are used as antiemetic during travelling (motion sickenss) proheptadine has been indicated as the appetite stimulant in dogs and cats

Used for anxiety disorders in dogs and cats like inappropriate urination associated with anxiety, excessive unexplained nocturnal activity such as pacing and vocalization and pruritus associated with anxiety .Doxepin, has proved more useful than other antihistamines for the treatment of anxiety-related pruritus and self-mutilation.

Adverse effects

CNS depression (lethargy, depression, drowsiness,somnolence) which may resolve after 3–7days, even if antihistamine administration is continued. Anticholinergic effects (dry mouth, throat, noseand eyes; urinary retention or dysuria; intestinalatony) An increase in pruritus has occasionally been recognized in dogs treated with with higher dosages of the drugs

Overdosage-Excitement (restlessness, nervousness, tremors,hyperactivity), due to reduced seizure threshold;Gastrointestinal effects (anorexia, vomiting, diarrhea,constipation) which may be prevented if the drugs are givenwith food; Cardiovascular effects (tachycardia, arrhythmia,hypertension) after overdosingwith some antihistamines.

Contraindications and Precautions: include avoiding the concurrent administrationof : monoamine oxidase inhibitors (e.g.selegiline,amitraz), or CNS depressans.; Astemizole or terfenadine with ketoconazole, itraconazole, fluconazole,clarithromycin; phenothiazine antihistamines, diphenhydramine with antidiarrheal mixtures (e.g.kaolin/pectin),antacids, adrenaline. Not recommended in animals with hepatic,cardiovascular disease, glaucoma,


134

hyperthyroidism , history of seizures,urinary retention , intestinal atony. There is no detailed information on the safety of administration during pregnancy or potential effect of milk. Treatment of antihistamine toxicosis: primarily symptomatic and supportive. Induction of Emesis, Activated charcoal, useful for recent ingestion. Diazepam to control seizures Physostigmine to counteract the CNS anticholinergic effect .

Dose: Amitriptyline:1–2 q.12 h (dog); 5–10 q.12–24 h (cat); Astemizole : 1mg/kg q.12–24 h (dog); Azatadine- 1 mg/dog q.24 h (dog); Brompheniramine- 0.5–2, q.12 h (dog); Cetirizine- 0.5–1, q.24 h(dog);Chlorpheniramine-0.2–2 q.8–12 h (dog)2–4,q.12–24h(cat); Clemastine-0.05–1.5 q.12 h(dog);0.68 q.12 h (cat);Clomipramine 1–3, q.24 h; Cyproheptadine- 0.1–2, q.8–12 h(dog) 2q.12 h (cat); Dimenhydrinate-8,q.8 h (dog);Diphenhydramine- 1–4q.8 h (dog)2–4,q.12h(cat);Doxepin-0.5–1 ,q.8–12 h(dog); Doxylamine-1–2, q.8 h(dog); Hydroxyzine 2–7 q.8 h (dog); 5–10 q.8–12 h; Ketotifen- 2–4 mg/dog q.12 h; Loratadine -0.5 q.24 h(dog);Oxatomide 0.5–2 q.12 h (dog) ,15–30 q.12 h (cat); Promethazine 1–2.5 q.12 h(dog)5 q.24 h (cat); Pyrilamine 1–2 q.8–12 h(dog); Terfenadine 0.25–10 q.12–24 h (dog); Trimeprazine 0.5–5 q.8–12 h(dog); tripelennamine 1 q.12 h (dog).H2 RECEPTOR ANTAGONISTS (H2 BLOCKERS)They are competitive inhibitors of histamine at the gastric parietal cell H2 receptor by blocking the H2 receptor; thus effectively blocking the gastric acid secretion .They strengthen gastric mucosal defenses against ulceration, enhances cytoprotection. Cimetidine, ranitidine, nizatidine and famotidine are the common ones.Cimetidine reduces the metabolism of other drugs by inhibiting hepatic microsomal enzyme systems. Potencywise:Famotidine> nizatidine >Ranitidine >cimetidine. Food delay the absorption of cimetidine, has minimal effect on ranitidine, and enhances absorption of famotidine .

Indications: 1.Peptic Ulcer, Gastroesophageal Reflux,Dyspepsia,in monogastrics 2.Gastric ulcers in canines, foals, and pigs. 3. Prolonged inappetence in ruminants 4. Abomasal ulcers in cattle and calves. Abomasal ulcers are common in high-producing cows within the first 6 wk after parturition. The most likely cause is prolonged inappetence, which results in sustained periods of low abomasal pH. The adverse effects of cimetidine include: hypotension. , dizziness, confusion, diarrhea, constipation, and rash, gynaecomastia in males, loss of libido, impotence,( antiandrogenic) which are reversible upon discontinuation

Interactions: Antacids reduce the absorption; are to be administered at least 1 hour interval . Cimetidine inhibits hepatic microsomal enzymes and may may increase the serum concentrations to toxic levels of drugs like: theophylline, phenytoin, lidocaine, ,


134

propranolol,tricyclic antidepressants, benzodiazepines, sulfonylureas, metronidazole. Contraindications : neonates, hepatic,renal insufficiency

Dose: Cimetidine-Dogs: 5-10 mg/kg, PO, QID Horses: 4 mg/kg, IV, BID; 18 mg/kg, PO,BID; Raniitidine-Dogs, cattle : 0.5 mg/kg, PO, SC, or IV, BID Horses: 1.3 mg/kg, IV, BID; 11 mg/kg, PO, BID Famotidine-Dogs: 0.5-1 mg/kg, PO, IV, SID Horses: 0.4 mg/kg, IV, BID; 3 mg/kg, PO, BID

*****


134

ADVANCES IN CHEMOTHERAPEUTIC PROTOCOLS IN POULTRY

Sandeep Halmandge

Disease is deviation from the normal state of health; it could be due to bacteria, Viruses, Fungi, Protozoa, Parasites or nutritional or other causes. In poultry industry productivity, profitability is enhanced by application of principles of bio-security, vaccination, management and understanding and prevention of emerging diseases of economic importance. Improved bio security and appropriate vaccination reduces the risk of disease. There are several diseases which causes severe economic losses to this industry either in the form of decreased egg production, meat production or from mortality.

Some of the important diseases of poultry which are of economic concern are listed here.

Disease Name & Etiology

Transmission Clinical Appearance

Pathology Diagnosis Treatment and Prevention

BACTERIAL DISSEASES

Pullorum / Bacillary White Diarrhea

Etiology : Salmonella pullorum

Vertical transmission

(Trans ovarial route), Horizontal Transmission by direct contact with affected birds, indirect contact with equipments

Depressed, Anorectic and tend to huddle under brooder, Cupious white diarrhea which will be adherent to the plumage surrounding vent, stunted growth and lameness due to arthritis, and huge mortality at 2-3 weeks of age.

Spleenomegaly

Hepatomegaly

Inflammation of the naval

( omphalitis ) and focal abscess on heart, lung and liver

Isolation and Identification of the bacteria by culturing

Treatment is of not much helpful only it reduces the severity of the disease. Sulphadiazine / Sulphaguinadine at 0.5-0.75 % conc. in feed or 1 gr/1 Ltr of water for 5 days.

Chloramphinicol ( 0.5 % ) in feed for 10 days or 1 gr per 5 Ltr of water.

Chlortetracycline


134

-200 mg/kg i.m

Enrofloxacin – 10 mg/kg i.e 1 ml per 1 ltr of water.

Fowl Typhoid

Etiology: Salmonella gallinarum

Vertical Transmission

(Trans ovarial route), Horizontal Transmission by direct contact with affected birds, indirect contact with equipments

Peak mortality at 2-3 weeks after outbreak, affected bird are sleepy, poor growth, Sudden drop in feed intake, Diarrhea, depression, Decreased egg production ( but these signs are not of diagnostic)

Spllenomegaly

Hepatomegaly

Inflammation of the ovary, peritonitis, greenish bronze sheen on the liver surface upon exposure to air and focal abscess on heart, liver. and liver

Isolation and Identification of the bacteria by culturing

Sulphamerazine -0.2 %conc. in feed for 5 days ror 1-2 gr / Ltr of water.

Furazolidone -0.01- 0.04 % in feed for 10 days or 2 gr per tonne of feed or 1 gr/ ltr of water.

Enrofloxacin-5 mg/kg, i.e. 1 ml per 2 ltr of water.

Vaccination at 8 and 10 week of age

Avian Paratyphoid

Etiology :

S.typhimurium

S.virchow

S.agona

S.enteritidis

Vertical Transmission

(Trans ovarial route), Horizontal Transmission by direct contact with affected birds, indirect contact with equipment

High chick mortality, huddling with profuse watery diarrhea

Hepatomegaly, Spleenomegaly

Inflammation of the ovary, peritonitis, focal abscess on heart, liver.

Conformation is by isolation & identification of organism, lesions,

Specific ELISA Kits are available for detecting Anti bodies against

Sulphadiazine / Sulphaguinadine at 0.5-0.75 % conc. in feed or 1 gr/ltr of water.

Chloramphinicol ( 0.5 % ) in feed for 10 days

Chlortetracycline -200 mg/kg i.m

Furazolidone at 0.04 % conc. in feed for 2 weeks or 1 gr/ ltr of


134

S.enteritidis

water.

will suppress the mortality but not eliminate infection.

Avian Pasturellosis/Fowl cholera/ Avian HS

Etiology: Pasturella multocida

Direct contact with infected birds, rodents, wild birds. Indirect by Contaminated feed and water, saliva, feces.

Incidence is more when birds attain maturity with high mortality and morbidity. Sudden death without any signs, poor appetite, Mucous discharge from eye, nostrils and mouth, diarrhea, cyanosis of comb and wattle, swollen foot pads, tracheal rales and torticolis due to otitis interna.

Spleen and liver enlargement with hemorrhages on viscera, heart and Ovary. Yolk material in the peritoneal cavity. Hemorrhagic lesions in the respiratory tract.

Clinical signs

PM lesions

Isolation and identification of the bipolar organism from liver impression smears and lab. Animal inoculation test.

Tetracycline -0.02 to 0.04 % in feed or 5 gr per 4.5 ltr of water will reduce the mortality and clinical signs.

Chlor tetracycline-40 mg/kg i.m

Erythromycin-1 lb/ 500 gallon of water

Chloramphinicol- 20 mg/kg i.m or 1 gr in 5 ltr of water.

Vaccination at 6- 8 weeks of age. Repeat at 14-16 weeks of age.

Staphylococcal infection

a) Arthritis/

Tenosynovitis

Staphylococcal species

a) Swollen hock joint, lameness, arthritis of phallengial joints

a)synovial membrane of joint/ tendon sheath is thick and edematous with fibrin depositb) lesions are dark, moist and

Clinical signs

PM lesions

Isolation of the organism

Chortetracycline -40 mg/kg i.m

Streptomycin-150 mg/bird

Sulphaquinnalone-0.05% in drinking water

Ampicillin –


134

b) gangrenous dermatitis

c) Sub dermal abscess

( bumble foot disease)

d) yolk sac infection

( mushy chick disease)

b) All age of birds are affected, wing tip and dorsal pelvic region most affected

c) Affects more mature birds/ heavy breeds, undersurface of the foot is affected.

d) High chick mortality, yolk sac infection, distended abdomen, huddling tendency

gangrenous in appearancec)

d) Prominent with necrotic naval, inflamed, unabsorbed yolk sac with yolk abnormal in color.

1gr/ltr of water for 4 -5 days.

Doxycycline – 1 gr/ltr of water for 3 -5 days.

Enrofloxacin – 5 -10 mg/kg b.wt. for 3-5 days.

Infectious Coryza/ fowl coryza

Etiology : Haemophillus paragallinarum

Direct contact with affected birds, indirect contact with equipment, personal. Aerosol transmission

Seromucoid nasal discharge, conjunctivitis, edema of the face, swollen wattles, decreased egg production

Severe conjunctivitis with edema of the face and inflammation of periorbital fascia, sinusitis

Isolation of organism from sinus swabs/ nasal discharge. And from

Clinical signs

Tetracycline -0.04 % in water or 5 grper 4.5 ltr of water.

Chlortetracycline – 40 mg/kg i.m

For immature birds- sulphamethaxazole-0.5% in feed for 5 days or 1-2 gr per ltr of water.

VIRAL DISEASES


134

Marek’s disease

Etiology: herpes virus

Horizontal transmission -infected birds feather dust contaminate with virus, maybe distributed by wind, equipment/personal also by inhalation

5 to 35 weeks of birds are affected with mortality may reach as high as 50 %. Weakness of legs which lead to paralysis of legs, wings. Depression, ataxia, blindness, pupil is irregular and will be small pin point opening, impaction, diarrhea, torticolis

Enlargement of feather follicles on the skin

Enlargement of peripheral nerves of sciatic and brachial plexus

Neural lesions are diagnostic, histological examination of nerves will show lymphocytic infiltration

Day old chick vaccination.

Infectious Bursal disease/ Gumboro disease

Etiology : RNA virus/ avibirna virus strains

Direct contact of young birds with infected birds. Indirect contact with contaminated equipment, houses, clothing and personal

Variable morbidity and mortality in young chicks of up to 6 weeks of age, whitish watery diarrhea, depressed, recombancy, ruffled feathers.

Muscular hemorrhages in the dead birds, enlargement o bursa of fabricius which is surrounded by gelatinous exudates

Bursal changes are diagnostic, by symptoms and lesions, and by virus isolation

No treatment

Vaccination at 18- 21 days of age by drinking water repeat at 7 week.

New castle disease/

Inhalation and ingestion

Causes high morbidity and high mortality. Hemorrhages

on digestive


134

Ranikhet disease

Etiology : Avian paramyxovirus type 1

of contaminated feed and water

Velogenic Viscerotropic virus – causes acute onset, cessation of respiration, respiratory and nervous signs with high mortality (100 %)

Mesogenic virus – nervous and respiratory signs with less lethal disease. Decrease egg production

Lentogenyc virus – mild respiratory infection with high morbidity

tract especially on proventriculus. Severe trachitis, pulmonary congestion.

Conjunctivitis, with mild hemorrhagic trachitis.

Symptoms, PM lesions, Isolation of virus from lung, spleen, trachea, chloacal swabs.

No treatment.

Vaccination:

F-strain ( lasota) to day old to 7 day of age

R2B (Mukteshwar strain) at 8 – 10 week of age.

Infectious Laryngeotracheitis

Etiology : Herpes virus

Inhalation, direct contact with infected birds, indirect contact with contaminated equipment and personal

Sudden onset of respiratory signs like

(snicking/gurgling), Stretched neck with open mouth breathing, dyspnoea,

Hemorrhagic tracheitis with blood clots, caecious exudates in the trachea

Symptoms and lesions. Isolation and identification of virus from the tracheal contents.

No treatment because of existence of carrier state. Only symptomatic therapy with antibiotics will reduce the severity.


134

conjunctivitis, swollen head, expelled cough material contaminated with blood or blood clots

Vaccination at 10 -16 week of age

Avian infectious bronchitis

Etiology : Corona virus

Direct contact of young birds with infected birds. Indirect contact with contaminated equipment, houses, clothing and personal

Decreased egg production with malformed shells, low flock mortality, sneezing, respiratory rales (gurgling) with ocular discharge.

Red discoloration of trachea and accumulation of mucus in nasal cavity

Symptoms and lesions.

Isolation and identification of virus by egg inoculation.

No treatment

Vaccination with Massachusetts / Connecticut strain, at 2 – 3 weeks of age and repeat at 4 – 6 weeks of age.

Avian Influenza

Etiology : Type A orthomyxovirus having

Haemagglutinating (HA) and Neuraminidase (N) antigen on the surface.

Indirect infection occurs by moving flocks, equipments, and personal and by wind dispersal (aerosol).

Direct infection occurs between infected carrier and susceptible

High Pathogenic Avian Influenza (HPAI) result in sudden decline in egg production with rapid increase in mortality along with respiratory and nervous signs. Sneezing, coughing, rales, cyanosis of comb and wattle, edema of head/face are commonly

Subcutaneous hemorrhages and odema of the head. Vesicles on the comb/wattle. Hemorrhages on respiratory tract and lymph nodes of the intestine.

Isolation and identification of the virus using serum virus neutralization. ELISA Kits are available for sero- surveillance of antibodies.

No treatment

Slaughter and disposal of the affected flocks. Quarantining of the affected area, restriction of the movement of the flocks, products from the area of infection.


134

flock. noticed.

PROTOZOAN DISEASES

Coccidiosis

Etiology: Various Eimeria Sps

E.acervulina

E.mivati

E.nicatrix

E.maxima

E.tenella

E.brunetti

Sporulated oocyst can be transmitted mechanically by personal, contaminated equipment. Also ingestion of contaminated feed and water

Sudden onset, depression, ruffled feathers/plumage, diarrhea, pale comb and wattle and blood mixed caecal droppings (Dysentery )

Hemorrhages on intestine especially duodenum and jejunum, white foci/lesion on the serous surface of the intestine. Intestinal contents are mixed with blood and mucus.

Signs of diarrhea and dysentery. Microscopic examination for the demonstration of oocyst.

Sulphaqunaxline at conc. 0.1% for 3 -5 days. Or 30 gr in 20 ltr of water

Amprollium soluble powder 0.012 – 0.024 % for 3- 5 days. Or 30 gr in 25 ltr of water.

Nitrofurazone and furazolidone combination- 1 gr/ltr of water.

ENDOPARASITIC INFESTATION

Ascardias

is

Etiology :

A.galli

Heterakis gallinnaru

Ingestion of contaminated feed and water, also intermediate hosts like cockroaches, earthworms.

Reduced egg production, Death may occur due to intestinal obstruction.

Stunted/debilitated birds.

Easily seen upon PM examination., catarrhal enteritis.

Fecal examination for the egg

Piperazine -50-100 mg per bird.

Levamisole- 5 gr/100 birds.


134

m

Cestodal Infestation

Etiology:

Hymenolepsis spp

Raillietina spp

Ingestion of intermediate hosts like ants, beetle and flys.

Decreased weight gain, diarrhea with mucosal shreds.

Tape worms are readily seen, catarrhal enteritis with fluidity is observed in the intestinal lumen

Fecal examination for the egg

Niclosamide 0.5 gr/kg

Dichlorophen – 0.3 gr/kg orally

Vaccination Schedule in Poultry:

Vaccination involves administration of an antigen to stimulate the immune system to produce specific antibodies against viral, bacterial and protozaol disease. Vaccination programme should be based on these following considerations:

Disease prevalent in the area, risk of exposure, immune status of flock, cost of acquisition of vaccine, availability of specific vaccines, cost to benefit ratio associated with vaccination taking into account the risk of infection and financial losses from the disease.

Vaccination schedule for Layers:

Disease Vaccine Age (weeks) Dose & route

1. Marek’s disease HVT vaccine Day old 0.2 ml im or sc

2. Ranikhet disease Lasota vaccine 1st 1 drop in eye/nostril

3. Gumboro disease Gumboro (live) 2 - 3rd 1 drop in eye/nostril

4. Infectious bronchitis IB live Massachusetts

strain vaccine

4th Drinking water

5. Ranikhet disease Lasota vaccine 4 – 5th Drinking water


134

6. Fowl pox Fowl pox vaccine 6th Wing web prick

7. Ranikhet disease R2B vaccine 8th 0.5 ml im or sc

8. Infectious coryza Infectious coryza killed 8th 0.5 ml im or sc

9.Fowl Cholera Fowl cholera killed 8th 0.5 ml im or sc

10. Infectious coryza Infectious coryza killed 12th 0.5 ml im or sc

11.Fowl Cholera Fowl cholera killed 12th 0.5 ml im or sc

12. Fowl pox Fowl pox vaccine 14 - 16th Wing web prick

13. Ranikhet disease R2B vaccine 18th 0.5 ml im or sc

14. Gumboro disease Gumboro (killed) 18 – 20th 0.5 ml im or sc

*****


134

CLINICAL ASPECTS OF ANTIMICROBIAL DRUG INTERACTIONS

SUNILCHANDRA.U

Drug interactions can reduces the effect of the ‘ primary/target drug” (the drug already there) or increases the toxicity of the target drug – often perceived as an adverse effect of one of the drugs because of increased drug concentrations and on very few occasions these drug interactions may be beneficial in increasing the overall activity.

Incompatibility: Mixing of certain drugs together in the same syrienge or with intravenous fluids may lead to physical incompatibility (change in turbidity or colouration) or chemical reactions (viz; hydrolysis, oxidation, reduction or complex formation) and thereby loss of pharmacological activity. The vehicle/ stabilizers /preservations used in the product may also cause drug interaction

Solutions may be incompatible with other solutions because of ionic interactions. For example sodium bicarbonate will react with calcium-containing solutions, forming calcium carbonate.

Fluoroquinolones should not be mixed with cation-containing fluid solutions, when given by intravenous route. Admixing tetracyclines with calcium-containing solutions will result in precipitation. It is not advisable to mix salts of hydrochloric acid (HCl) (e.g., dobutamine HCl, dopamine HCl, and epinephrine HCl) with alkaline solutions. Vitamin B1 (thiamine hydrochloride) is unstable in alkaline solutions and should not be mixed with alkalinizing solutions, carbonates, or citrates. Caution to be exercised in administration of fluids, especially those containing sodium ions, to patients receiving corticosteroids

Potassium containing solutions should be used with caution in the presence of cardiac disease, particularly in digitalized patients or in the presence of renal disease. Solutions containing lactate ions should be used with caution as excess administration may result in metabolic alkalosis. The solution has to be clear and container undamaged. It is always better to discard unused portion of the solution.

Incompatibility may result in failure to get desired response, untoward responses like febrile response, venous thrombosis ,phlebitis, extravasation and hypervolemia.

Normal saline, comparatively appears to be the most compatible intravenous fluid among all, for most of the antimicrobial drugs. The admixture of any drug with other medications in the same syrienge or intravenous fluid bottle is generally not


134

recommended as it may result in substantial mutual inactivation and drugs should not be mixed in infusion or syrienges unless the componments are of known compatibility.

Antibacterial drugs can be classified by their action as time-dependent or concentration-dependent. If the drug is concentration-dependent, usually a once-daily regimen can be administered effectively as long as a sufficiently high dose is administered. When treating a pathogen for which emergence of resistance is a concern, a higher dose may be justified, but the interval remains the same (e.g., once-a-day). A time-dependent antibiotic, on the other hand, does not produce better bacterial killing with higher concentrations. Activity is improved with longer exposure. Therefore, for these drugs, a long half-life is beneficial. If the drug has a short half-life (e.g., a cephalosporin or penicillin a constant rate infusion may improve therapeutic success

Examples of antimicrobial interactions of veterinary importance

Drug Interacting agent (drug) Result/adverse effect

Fluoroquinolones Na+ and Cl-. Aluminum, Iron, calcium, and Mg+2 , antacids

Theophylline(methyl xanthines)

NSAIDS

Decrease absorption

CNS stimulation-Convulsions

Increased risk of seizures

CNS Depressants Antihistamines, opioid analgesics, Phenothiazine derivatives

Enhanced depressant effets

Tetracyclines (oral)

Antacids , Calcium supplements, Milk, Iron supplements, Magnesium-containing laxatives, Sodium bicarbonatePhenobarbital or Microsomal enzyme inducers,

Chelation and reduced tetracycline absorption

Reduce efficacy

Digitalis Phenolphthalein (laxative), antihypertensives

Abnormal rhythmicity

Acid labile drugs like erythromycin

Anticholinergic drugs (eg: atropine) Decrease absorption

Linocomycin Antidiarrhoeals-kaolin, pectate

Chloramphenicol, erythromycin, neostigmine Opioid analgesics

Decreased absorption

Antagonistic-reduced efficacy

Potentiate respiratory depression

Antibiotics administered per os in ruminants

Large dose of atropine Decreased bioavailability


134

Aminoglycoside Cephaloridine, cephalothin polymixins, furosemide, curare like drugs, anaesthetics, amphotericin

Nephrotoxicity, neuromuscular blockade

Chloramphenicol Dicoumarol, barbiturates Cyclophosphamide Phenytoin, Salicylates

Prolonged anesthesia, anticoagulation/ bleeding

Griseofulvin Dicoumarol, barbiturates Reduced anticoagulant effect

Monensin Tiamulin Neurotoxicity

Rifampin Theophylline Enhanced theophylline clearance

Sulfonamides Oral anticoagulants Prolonged anticoagulation effect

Oral hypoglycaemics(eg: tolbutamide)

Salicylates ,Chloramphenicol Phenylbutazone, long acting sulpha drugs

Severe hypoglycemic effect

Corticosteroids Acetazolamide

Antidiabetic drugs

Barbiturates

Diuretics

Metoclopramide

NSAIDS

Increased hypokalemic risk Antagoniosm of hypoglycaemia

Increased risk of hypokalemia

Antagonism of diuretic effect,

Aggression

Risk of GIT ulceration

Phenobarbitone Barbiturates Chloramphenicol Corticosteroids Progesterone Testosterone Thyroxin,Griseofulvin,Phenytoin Phenylbutazone Cyclophosphamide

Cross tolerance can exist between many of them

Warfarin phenylbutazone,phenytoin salicylate,sulphinpyrazone

Increased warfarin toxicity

Decongestants in cold and cough (antihistaminics)

Diuretics Aggravate high blood pressure

Antihistamines used for allergies and colds,

Barbiturates, tranquilizers, CNS depressants

Increased sedative effects

NSAIDS Anticoagulants, corticosteroids

Diuretics,beta blockers,ACE inhibitors Sulfonylureas

Risk of excessive bleeding

Reduced antihypertensive effect

Increased hypoglycaemic effect

Ketoconazole Antacids , H2 receptor antagonists ,Sucralfate


134

Omeprazole,Isoniazid Rifampin, Phenytoin , Carbamazepine Phenobarbital

Reduced absorption and efficacy

Antidiarrhoeal medication (e.g., diphenoxylate)

tranquilizers (e.g., diazepam), sedatives

increased effect of tranquilizers, sedatives

Fat-soluble vitamins

Mineral oil Reduced absorption of the vitamins

Cephalosporins

Antacids, H2 recpetor amatagonists

Nephrotoxci mediactions- Aminoglycosides, Diuretics

anticoagulants

Reduced efficacy

Potentiate nephrotoxicity

Potentiate bleeding

Macrolides(eg: azithromycin eryhthromycin)

Chloramphenicol , Florfenicol, Lincosamides, penicillins

xanthines

Antagonistic: - Reduced efficacy

Increased toxicity

Penicillins Chloramphenicol, tetracyclines , sulfonamides; phenyl butazone

Oral- Antacids

Antagonistic: - Reduced efficacy; reduced distribution

Decrease absorption

Levamisole Organophosphorous compounds, diethylcarbamazine

Enhanced toxicity

Metoclopramide

Antimuscarinic drugs, opioid analgesics,

butyrephenones, phenothiazines, corticosteroids

aspirin, paracetamol

Antagonism

Increased CNS signs

Increased absorption

Zinc salts Iron salts, tetracyclines Reduced absorption

Bacteriostatic antibacterials

Tetracyclines, sulphonamides, chloramphenicol, macrolide, spectinomycin,

Bactericidal antibacterials

Penicillins, cephalosporins, aminoglycosides, monobactams, carbapenems, fluoroquinolones, metronidazole etc

Tetracycline with

Inhibitors of protein synthesis:

Macrolide, clindamycin,

Bactericidals action will be

Ineffective

Interfere with one another’s


134

trimethoprim, clindamycin, fusidic acid, lincosamides

chloramphenicol , spectinomycin dalfoprostin, lincosamides

action against bacteria reducing the net effcet

*****


134

AN UPDATE ON HERBAL ANTIMICROBIAL AGENTS

Dr.Sagari Ramdoss

Anthra, an organization of women veterinary scientists working in the field of livestock production and development, has been involved since 1996 in a Research Project to document and validate local ethno -veterinary and animal management practices carried out by livestock rearing communities in different parts of the states of Andhra Pradesh and Maharashtra in India. Communal knowledge and innovations are an integral part of the day to day healing and management practices of farmers in all areas and over 80% farmers continue to use these because they are easily and quickly available, especially in remote villages. However this knowledge is today being rapidly lost. Farmers, both men and women, have expressed a keen desire to increase their own knowledge of these systems. This paper outlines the validation framework evolved by ANTHRA wherein farmers using these medicines are actively participating in an evaluation process. Major findings are that local practices are effective, participating farmers use them confidently and other farmers are keen to use and increase their knowledge of them.

In 1996 Anthra had initiated an action research on Documnetation of ethnoveterinary practices from six different regions of Andhra Pradesh and Maharashtra initiated a process of reclaiming their indigenous knowledge systems with respect to animal health. The entire process, which evolved through several stages, which can roughly be classified into stages of learning and documentation, community prioritization and social validation, wide spread dissemination, use and continuous innovation and in-situ conservation of IK related plant and animal genetic resources, was facilitated by Anthra, and has been widely described in several publications (Anthra, 1998; Anthra, 2006; Anthra 2008, 2009; Ghotge et. al, 2002; Ghotge N. 2004; Ramdas et. al., 2004, Ramdas et. al., 2009, Ramdas, 2009). The knowledge was fast disappearing and eroding, primarily due to a breakdown of the systems of oral transmission of knowledge couple with a loss of the genetic resources. We would like to reiterate and focus on the pro-active and preeminent role-played by women at every step of the process of taking back control over the knowledge system, from its inception to today.

The process began with young members of the community, of whom half were young women, apprenticing with knowledgeable elders and healers-both women and men, from whom they learnt-. They documented the knowledge in different ways- written, visual, photographic, stories, as also learnt practically. A total of 126 disease


134

conditions/symptoms in Maharashtra and 61 disease conditions in Andhra Pradesh affecting livestock (large ruminants, small ruminants, camels, donkeys, pigs, poultry) were documented. Diseases ranged from contagious diseases, diseases of the digestive, respiratory, reproductive and urinary systems, to skin diseases and simple surgical conditions. While a number of home remedies were known to farmers--men and women, certain remedies were known exclusively to specialist healers. A total of 1223 treatments in Maharashtra and 1186 treatments in Andhra Pradesh were documented. The same treatments for the same disease were cited by more than one healer/farmer, and there were numerous common treatments documented from all six regions. There were single and mixed-plant treatments as also animal-based and chemical ingredients used in treatments. Numerous plants were used for multiple purposes. Trees, herbs, climbers, shrubs, grasses, legumes were used in treatments. The stem bark was the most commonly used part, followed by leaves, seeds, roots, fruits and flowers (Anthra, 2006).

Women were key in the subsequent phase of “social validation”, where over 32 women from their communities, used the practices of their mentors- who were the traditional healers and elders, to prevent and treat a variety of disease conditions. Of the total diseases documented, 20% of the diseases were prioritized for further validation. The treatments for these prioritized diseases constituted 25% or one-fourth of the total documented treatments. One hundred twenty treatments (20%) were categorized as A, 372 (64%) as B treatments and the remaining 15% treatments were in the C category. Forty-four per cent or 165 of category B treatments were used in field trials between 2000-2003. Nine hundred ruminant cases were treated. Of these, an average 92% of the cases were cured and 8% were not cured. Similarly, 1777 poultry were treated with a success rate of 100 per cent. Finally, a total of 20 treatments for 10 disease conditions in ruminants and poultry in Andhra Pradesh, and 14 treatments in 8 disease conditions in Maharashtra met the set criteria and have been socially validated and were widely disseminated to farmers in the community for their further use (Anthra, 2006).

Women played a similar key role in the validation of traditional fodders. Women continued to play a key role in taking the knowledge back to the community- through sharing the practices with the village level women’s groups, sharing the information and approach with communities in other areas, becoming trainers who in turn trained new community volunteers and sharing experiences through jatras and campaigns. Anthra, was able to make the knowledge accessible to the younger generations with literacy skills, through low-cost publications in local language, school textbooks, and audio-visual learning materials.


134

In the context of Anthra’s work with communities, the impetus to study ethnoveterinary medicine came particularly from women farmers, who have historically been denied access to many aspects of this body of knowledge, since practices have been primarily transmitted from father to sons and only rarely to daughters. They wished to know remedies that are easy to prepare, effective, readily available, inexpensive and which could be used confidently. They also wanted to learn to recognise conditions that cannot be treated with local remedies but need other kinds of management.

Some of the key findings with respect to ethno-veterinary practices were:

While indigenous knowledge and practices exist in every area and over 85% of farmers –both women and men in all regions prefer ethno-veterinary treatments as the first choice for treating their animals, it is becoming increasingly difficult for them to use it mainly due to the absence of healers, breakdown of traditional systems of knowledge transmission, rapid depletion of local bio-resources on which this knowledge depends and emergence of new “problems” for which local innovations alone are inadequate. No single person or individual has access to “all components of the communities knowledge”. While the majority of members within the community universally shared parts of this body of knowledge, other information was known to only a few.

In quite a few areas, people were scared to discuss their practices, as they believed the government had banned its use.

Ethno-veterinary practices documented in each area are almost entirely linked to the local flora and fauna of the area. Regions that shared similar agro-ecological features and thus flora type- share a greater number of common etho-veterinary practices than those that were agro-ecologically very different.

While women perform between 50-90% of all day to day activities related to the care and management of livestock and poultry, they have been effectively excluded from the vast body of ethno-veterinary practice. 99% of all specialized healers are men and transmit information only to sons. Women however are seen to have developed expertise and knowledge on ethno-veterinary management practices specifically for the young, pregnant, lactating animals and poultry.

Farmers - especially women are keen to obtain guidelines for the proper use of ethno veterinary treatments, as they observe that some treatments are effective and others are not.

With loss of bio-resources required for ethno-veterinary remedies- there is a growing


134

body of “new and dangerous practice” which are a crude mix of modern harmful drugs and chemicals that are readily available in today’s rural market with some “traditional” ingredients. Typical examples are using crop pesticides such as “Endosulfan with turmeric or naphthalene balls/gammexane to clean maggot wounds”.

The field validation commenced in June 1999. As of December 1999, AHW’s have been trained in the diseases that have been selected for validation. Select “B” category treatments are being used in the field since May 1999 (about 6 months). Treatments that have been categorized as “A” have been compiled in the local languages and disseminated to the communities in the project areas.

While it is still in its initial period, preliminary analysis indicates a virtual 100% success rate in the effect of the “B” treatments (Table 5.a & b), in a sense reconfirming our decision to place priority on empirical information while formulating a protocol for validation. Women, who knew nothing about treating animals, are today confidently using these simple and readily available remedies to treat cases. Where once healers were rigid about teaching this knowledge to women, today these very same healers look upon the women AHW’s as their partners- and jointly together are breathing new life into this knowledge system which was threatened with extinction.

In this model of social validation where farmers are actually actively participating in the validation process there remain many unanswered questions. For instance the wider academic community still insists upon “statistical significance “to prove the “validity” of a treatment. They may question the bias within this model of “in-situ” validation.

We are still trying to address the issue of “statistical significance”. On the one hand all the treatments have histories dating back hundreds of years. Under this protocol of validation the efficacy of these age-old treatments on sick animals; are being recorded “real-time”, possibly for the first time. There are some treatments that have been used and recorded under this current “social validation “ process maybe only 10 times, yet have produced a positive cure each time. While this may not meet the “numbers” required for statistical significance, the women who use these treatments are now so confident about their effect, that they will use it and share the knowledge with others. At a social level, the process of “personal use” convinces them of its “significance” and validity.

Our attempt in evolving this model of social validation is also in a sense to challenge the conventional paradigms of “validity” and put forth-new ones.


134

*****


134

HANDLING OF VETEROLEGAL POISONING CASES

M.VIJAY KUMAR

Every veterinarian will be encountered with diagnosing and treating the animals exposed to toxicant / poisoning which may be either accidental or malicious in origin.History, clinical signs and necropsy of the animals will assist in rapid tentative diagnosis which will help in the treatment of other affected animals in case of accidental poisoning. In case of malicious poisoning, which may turn up into veterolegal case, the identification of the toxin/poison is a must to establish the cause of death. In all poisonous/toxicological cases, chemical analysis of the biological specimens is essential to know the cause of death or illness. For which proper collection and despatch of toxicological specimens to the laboratory is necessary.

History of the case is of great importance in the diagnosis of poisoning. This includes the number of animals in the farm, number of animals affected, and method of feeding, regularity of feeding, recent changes in the rations or attendants, spraying of pastures with pesticides or fertilizers, rodenticides, presence of poisonous plants in the farm environment. The possibility of industrial effluents coming in contact with grazing/watering sources etc.

Important aspect of Autopsies is to determine the date and time of death. Autopsists, generally know the time and date of death from owner of dead animal or from the clinical history forwarded by clinician or government farms. In Medicolegal (Veterolegal) cases, Autopsist is to determine the exact time and date of death of animal during post-mortem examination because police and court of law may like to know the time & date of death of that animal.

Determination of time & date of death is difficult work. After a regular examination of a good number of dead bodies, Autopsist will be able to gain experience to determine the time of death. After gaining the experience of several post-mortem examinations, determination of time of death becomes very easy. Do not send the material from medicolegal / veterolegal cases to any of the institute directly - send through police only. Some of the important points are mentioned below by which pathologist can determine the time of death. Indications as to when death occurred are obtained from the presence or absence of rigor-mortis, abdominal tympany, protrusion of rectum and an odour of putrefaction of dead body. It is very essential to examine the carcass very carefully for


134

post mortem changes. If the dead body is very fresh and not showing any P.M. change and blood clot is also of recent origin, it indicates that death has taken place 2 to 4 hours earlier from time of examination. If there are P.M. changes in the dead body, then time of death is determined on the basis of the presence of rigor mortis and on status of dead body. Rigor-mortis is the shortening and contraction of muscles which occurs after death. Due to Rigor mortis, body muscles become very hard, stiff and immobilize. Presence or absence of rigor mortis helps in determining the time of death because rigor mortis appears gradually in the body and also disappears in same order.

Rigor mortis first appears in the anterior portion of the cadaver (dead body) and progress in the posterior direction. It usually appears first in head, then neck then fore limbs, then trunk and finally in the hind limbs. It disappears in the same order. It disappears first head then neck then from fore legs then trunk and finally from hind limbs. 'Whole body again becomes loose. Rigor-mortis appears only once in the dead body. Appearance and disappearance of rigor-mortis take certain time after death and this time intervals of appearance and disappearance help in determining the time of death. These vary due to high and low temperature of the atmosphere.

Appearance of rigor-mortis causes whole body stiff in which mouth cannot be opened and joints of legs cannot be twisted. In the winter, rigor mortis appears in head within 2 to 8 hours after death but in the summer, it appears in the head in half to three hours after death. Rigor mortis appears in head, neck and fore limb in about 12 hours and in the whole body in about 15 hours after death. During autopsy if rigor mortis is present in the whole body, That means death has taken place between 15 to 20 hours earlier from the time of post-mortem examination. Disappearance of rigor mortis takes place in the same order. After 20 hours of death, hind limbs are only found stiff and other parts are loose. Disappearance of rigor mortis from whole body takes place in 24 to 30 hours and whole body becomes loose but putrid or obnoxious smell is found in the dead body. Decomposition or putrefaction is complete on the dead body after disappearance of rigor mortis. Disappearance of rigor mortis depends upon the rapidity with which decomposition occurs. The longer an individual has been dead the more advanced will be the changes of decomposition. This occurs after 24 to 30hours of death. The carcasses give obnoxious bad smell. Abdomen is distended with accumulated gas. Gas is produced as a result of bacterial fermentation in the stomach and other parts of the body.

So when the carcass is completely putrefied, it means death has occurred more than 30 hours earlier from the time of P.M. examination. While determining the time of death of an individual, atmospheric temperature and seasons are taken into account because the appearance of rigor mortis and putrefaction are hastened by high external temperature,


134

violent exercise (racing, fighting or struggling) or when violent muscular contractions have taken place as seen in death of tetanus or strychnine poisoning, likewise, rigor mortis is retarded by low external temperature (winter). In emaciated animal animals, rigor mortis appears very slowly. Sheep putrify more quickly than short coated animals, as the fleece keeps the heat in the body. Fat animals retain heat owing to poor heat-conduction property of adipose tissue.

Postmortem :

Necropsy by routine procedure is to be performed as soon as possible after the death of animal. The animal should be examined externally for the presence of any incisions (for sui poisoning, snake bite etc.,) on the skin or mucous membranes. The oral cavity is examined for corrosive lesions (acids/alkali) or changes in colour of mucous membrane (nitrate, co, cyanide poisoning). As most of the toxins gain entry through gut, examination of gut mucosa, the contents, their smell, colour and pH (acids, alkali, urea) is a valuable guide in diagnosing toxicoses. Poisoning by salts of heavy metals results in significant post mortem lesions but poisoning by alkaloids like strychnine produces very feeble lesions.

The natural orifices, sub-cutaneous fat tissue, muscles, bones and teeth (in fluorine poisoning), body cavities, and internal organs should be examined. The stomach should be punctured rather than cut open for examination to note the character of smell. Puncture ensures greater accuracy and a longer time smell. Some of the poisons emit characteristic smell like bitter almond in hydrogen cyanide poisoning, garlic odour in phosphorus poisoning, rotten garlic or horse radish smell in selenium, tobacco odour in nicotine, acetylene odour in zinc phosphide and ammoniacal odour in urea poiosoning.

The colour of stomach contents also to be examined as copper salts impart a greenish blue colour whereas picric and nitric acid impart yellow colour to the contents.

The contents of the stomach, small intestine and large intestine vary from traces to flakes of paints or lead objects, grains or baits, seeds etc. Blood should be examined for its colour and clotting characters. Cyanide poisoning imparts cherry red colour, arsenic imparts rose red colour and nitrate poisoning turns the blood to brown colour.

Examination of other visceral organs should be done in relation to their size, colour etc. Spleen size is decreased and colour is changed to dark brown or black in copper poisoning and spleen size is increased in mycotoxicoses. The description of morphological changes should be noted clearly and absence of changes should be notified.


134

Submission of specimens:

A complete set of tissues collected from PM examination should include the brain , eyeball, thymus, thyrioid, heart, lung, spleen, kidney, liver, urinary bladder, pancreas, lymphnodes, various sections of the gastrointestinal tract, ovaries, placenta, testes etc. In case of many animals being affected, sample from more than one animal should be used.

The following specimen samples are preferred to be sent for different suspected poisoning/

Sr.No.

Suspected Xenobiotic for Analysis

Specimen required

Amount required

Remarks

1. Ammonia/Urea

Whole Blood or serum

Urine

Rumen contents

5ml

5ml

100 g

Frozen or add 1-2 drops of saturated mercuric chloride.

2. Arsenic

Liver, kidney

Whole blood

Urine

Ingesta

Feed

100g

15ml

50ml

100 g

1-2 kg

--

3.Chlorinated hydrocarbons

Cerebrum

Fat

Liver, Kidney, Ingesta

½

100g

100g

Use only glass containers

Avoid aluminum foil for wrapping specimens

4. Copper

Kidney, Liver

Serum

Whole blood

Feed

Faces

100g

2-5ml

10ml

1-2kg

100g

--


134

5. Cyanide/HCN

Forage /Ingesta

Whole blood

Liver

1-2kg

10ml

100g

Rush sample to laboratory

Frozen in air tight bottle. Stomach contents in 1% mercuric chloride

6. Fluoride

Bone

Water

Forage

Urine

20g

100ml

100g

50ml

Ideal sample will be lesion seen in organal bone

7. Herbicides

Treated weedy

Urine

Ingesta

Liver, Kidney

1-2kg

50ml

500g

100g

--

8. Lead, Mercury

Kidney

Whole blood

Liver

Urine

100g

10ml

100g

15ml

Heparinized, do not use EDTA

9. Mycotoxins

Forages, Feed sample,

Liver, Kidney, Brain.

100g

100g

Airtight containers or plastic bags. Cloth bags for dry feeds

10. Nitrate/Nitrite

Forage/Ingesta

Water

Body fluids

1kg

100ml

10-20ml

Ingesta in chloroform or formalin filled air tight container

11.

Organophosphates and

Organocarbametes

Feed

Ingesta

Liver

Urine

100g

100g

100g

50ml

--

12. OxalatesFresh forage

Kidneys

100g

100gFixed in formalin


134

13.Sodium Chloride (NaCl)

Brain

Serum

CSF

Feed

100g

5ml

1ml

1-2kg

--

14. Znc phosphideLiver, Kidney

Gastric contents

100g

100g--

Packing:

1. Samples submitted to the laboratory should be individually packed and labelled so as to avoid any confusion about specimen identification. Sample should be -wrapped in foil to protect light sensitive compounds from degrading or frozen to prevent volatile compounds from escaping o. All specimens should be double bagged ans submitted in appropriate shipping containers to prevent leaking.

2. Following points to be taken in to consideration during packing the sample to be sent for the investigation .

3. Samples must be placed in strong waterproof plastic bags or wide mouthed glass container without adding any preservatives/fixative to the sample

4. The container tightly stoppered, properly sealed with paraffin sealing wax should be kept kept in a larger wooden box which is sealed in cloth

5. All the specimens are to be taken in separate containers (polythene jars/covers), securely tied, properly labelled with particulars of date, case number., organs collected, species, name of preservative used etc.

6. A sample of the preservative used, brief history of the case along with treatment given particulars should be sent

7. Details of the addresses of the sender and the address of the laboratory is written on outside the box which can be sent either through a messenger or by post

8. The sample should not come in direct contact with any absorbent material like cotton wool, gauze which will dry out the sample.

9. Empty used medicinal bottles, plastic mineral water bottles should not be used10. Glass containers if used , must be well protected to prevent breakage in transit , by

packing with sufficient absorbent material like sawdust, newspaper etc11. The containers should never be filled completely as fermentation may occur

particularly with stomach/ ruminal contents12. The samples transported at ambient temperature or higher must be provided heat

seal, screw caps must be reinforced with tape.


134

13. In case of the samples being transported in refrigerated or frozen state using ice pack/ waterproof frozen sachets, screw caps should not be used.

14. Rumen contents/vomitus is preferred to be sent to establish that the toxin has been ingested.

15. Liver, spleen and blood are preferred to establish toxin/ poison absorption.16. Kidney, urine and milk are preferred be sent for detecting toxin excretion.17. A sample of preservative in a separate sealed container to be sent particularly in

veterolegal cases18. The container with indelible pen / marker labelling must be sealed properly to

ensure that the original contents are not being tampered or so as to to provide proof for being tampered especially in vetero legal cases .

19. In case of small animals (poultry, small dogs, lab animals) the cadavers are sent as it is, in case of large animals the gastrointestinal contents are collected from the vicinity of changes in the gastric/intestinal mucosa. If there are no changes, a representative sample is collected, but in medium sized animals the stomach tied at oesophageal and duodenal end, intestine tied at both ends and bladder with tied ends is sent separately.

20. It is always preferable to send the specimens through a special messenger.21. In medico legal cases, the specimens should be sealed in the presence of a witness

a sample of the preservative used should be sent.

22. It is always better to have a duplicate sample stored properly in a refrigerator for future reference.

Preservatives :For visceral organs like pieces of liver, kidney, stomach, intestine, contents of a stomach and intestine saturated solution of sodium chloride can be used.Suspected plants or food can be sent to the laboratory without adding any preservative Ice pack/ waterproof frozen sachets, are used in case of the samples being transported in refrigerated or frozen state.Rectified spirit (95% ethyl alcohol) 1 ml/g of tissue is the ideal preservative for toxicological specimens. ( except in alcohol, phosphorous and carbolic acid poisoning conditions).Formaline should never be used for toxicological analysis of specimen samples as it hardens the tissue without giving scope for scraping and interferes in with the the analysis by making the extraction of poison much more difficult. . Blood, urine and serum should be refrigerated and never be frozen.The materials for histopathological examination can be kept in a fixative preferably 10 percent formalin in a wide mouthed glass container with proper labelling and well protected by cotton padding/ covering.


134

Labelling information:The samples being sent to the laboratory must be accompanied by proper protected labelling with all the details regarding the case, including the following information

1. Name and address of the doctor and the owner of the animal2. Animal identification characteristics-species, colour, age, sex, breed etc.3. Number of animals affected and number of animals dead4. Date of onset of symptoms and the death5. Clinical signs recorded by the doctor and symptoms noticed by the owner6. Type and the quantity of samples sending7. Post-mortem findings8. Suspected poison/toxicant9. Any other circumstantial fact or information which may assist the laboratory in

identifying the causative agent10. In veterolegal cases, the label containing the details is placed inside the specimen

container and another label is pasted on the wooden box/cloth covering the container. The sample is then sent to the forensic laboratory , with the forwarding letter ,a copy of request letter from the police and a copy of the postmortem report

*****


134

CLINICAL MANAGEMENT OF POISONINGS OF VETERINARY IMPORTANCE

B.KALA KUMAR

In veterinary field toxicities are often found as a result of ingestion of poisonous substances while grazing or through water. Suspicion of poisoning is also aroused when illness occurs in a number of previously healthy animals, all affected at a same time, sharing the same signs, necropsy findings, to the same degree of severity. Poisoning in most occasions is accidental in farm animals, but may occasionally be deliberate .

SOURCE OF POISONINGS

1. Insecticides:Insecticides are the major source of poisonings in livestock.. Most of the insecticides are basically ‘neurotoxic’, hence they may share some of the clinical signs, Insecticides can be classified in to following categories: 1. Organochlorines: Eg: Aldrin, Endosulfan, Lindane, Dicofol etc 2. Oraganophosphates. Eg: Acephate, Malathion, Parathion, Methyl parathion, Dimethoate, Phosphamidon,, Chlorpyriphos, Chlorfenvinphos, Monocrotophos etc 3. Carbamates. Eg: Carbaryl, Metacil, Dimetan, Pyramat etc. 4. Pyrethroids (Synthetic): Deltamethrin, Cypermethrin,Permethrin, Allerthrin etc. 5. Miscellaneous: Chloro-nicotinic acid (nicotine), Arsenic compounds,Captan

Organochlorines: By virtue of their high lipid solubility these agents can enter the neuronal membrane with ease and therefore interfere with normal functioning of the nerve membrane sodium channel. The clinical signs of toxicity can be broadly categorized in to:

Behavioural signs - Anxiety, aggressiveness, abnormal posturing, maniac symptoms like jumping over inanimate objects, wall climbing etc. Neurological signs – Hypersensitive to external stimuli, spasm and twitching of fre-and hind quarter muscles, fascicualtions of facial and eye lid muscles and variations in body temperature (subnormal temperature to hyperthermia, up to 116F). Autonomic effects: Marked salivation (normally thick/ sticky saliva), Mydriasis, frequent urination, defecation and lacrimation.

Organophosphates: Clinical essentially appears as a result of irreversible inhibition of AChE, causing accumulation of acetylcholine in the neuro-muscular junction leading to ‘spastic paralyses. The cause of death is due to respiratory collapse. Muscaranic signs (miosis, watery, drooling saliva, urination, colic and /or defecation, lacrimation are the


134

common signs followed by nicotinic effects (muscle fasciculations, tremors) and C.N.S effects( ataxia, convulsions and later depression of respiratory and circulatory centers). Hypotension, bradycardia and dyspnoea are observed in poisoned animals.

Carbamates: The inhibition of AChE enzyme by carbamates is ‘reversible’, therefore, on most occasions animals recovers on own unless ingested large quantity of pesticide.

Synthetic pyrethroids: Although these compound process low insect: mammalian toxicity ratio, treatment of poisoned animals may be a difficult task probably because of multiple mechanisms involved in toxicity and variations among pyrethroid class (type-I & type-II). Hypersalivation, lacrimation, mucoid nasal discharge, excitement, in-coordination, extension of limbs are observed in deltamethrin toxicity in buffalo calves. Few pyrethroids also cause contact dermatitis.

2. Rodenticides:.

Anticoagulant rodenticides: These include warfarin (less used now a days) and second generation anticoagulant rodenticides viz: Bromadiolone , brodifucoum. The main source of poisoning is the ingestion of residues of the rodenticides or baits intended for killing rodents.. The poor coagulation mechanism cause massive internal haemorrhages over aperiod of time. Normally after period of about 2-5 days clinical signs appears and these include anorexia, pulmonary coughing (epitaxis, dyspnoea),hypothermia, haematuria, stiffness of hind quarters and sudden death. Internal haemorrhage, blood in the GIT(gastroenteritis), haemopericardium and menigeal/cerebral bleeding and haemorrhages in joints are the pathological lesions one can observe during necropsy. The affected animals should be shifted to quiet and warm place and the line of treatment include Vitamin-K1 in physiological saline (Vitamin-K3 not recommended) and cardio-vascular support.

Zinc phosphide/ Aluminium phosphide: It is one of the cheapest and quite effective rodenticide. Monogastric species are more sensitive rather than ruminants. Clinical signs include anorexia, lethargy, abdominal pain, bloat (in ruminants), deep respiration, ataxia, prostration and dyspnoea, gasping, convulsions and death. Post-mortum lesions include pulmonary congestion, edema, sub-pleural haemorrhages, congestion of liver and kidneys. Acetylene odour may be detected in stomach. No specific treatment is possible, however symptomatic and supportive care maybe given. Gastric lavage with 5% Sodium bicarbonate, Calcium boro-gluconate injection, anticonvulsants and measures to prevent shock can be undertaken as a life saving measure.


134

3. Herbicides & Fungicides:Dinitro-compounds: Dinitrophenol, DNP; dinitro-orthro cresol, DNOC); are some of the commonly used as herbicides. Accidental ingestion of foliage sprayed with these compounds may lead to toxicity in ruminants. These compounds induce methaemoglobinemia (intravascular haemolysis),hyperthermia, dark coloured blood and gastroenteritis. Rapid onset of rigor mortis, yellowish-green coloured tissues/urine may be recorded during post mortem examination.

Zeneb & Thiram: Zeneb (Zinc-ethylene dithiocarbonate) and Thiram (Tetra-methyl thiuron sulfide) are the two most commonly used fungicides in agricultural practice. Although acute poisonings is less likely to observe in field, chronic toxicities may get unnoticed. Zeneb can induce thyroid hyperplasia, hypothyroidism, degenerative changes in myocardial, skeletal tissues and depletion of testicular germ cells. Thiram exposure may cause conjunctivitis, rhinitis, bronchitis, abortion (ewes) and teratogenic effects.

4. Hydrocyanic acid (HCN) /Cyanide:The most prevalent form of HCN poisoning in livestock is caused by various cyanogeneetc plants capable of producing hydrocyanic acid. Such plants contain cyanogenetic glucocides (dhurrin in sorghum, amygdalin in bitter almond etc.) which hydrolyzed in to HCN in ruminants. Wilted, drought affected, injured (chopping, rinsing etc.) plants are more dangerous than fresh plants because of their preformed HCN. Any plants possessing 20mg HCN per 100gm (wet wt.) may serve as potential source of HCN poisoning. Other source of cyanide poisonings are: industrial grade Na/K and calcium cyanide (also fertilizer) and effluents from vicinity of electroplating/metal coating industries workshop.

Hyperoxygention of blood would lead to cherry red/ bright red colour of venous blood . Intoxicated animals shows salivation (frothy), bradypnoea, mydriasis, ataxia,tremors, epileptiform scizure, cardiac arrhythmia and clonic-tonic convulsions. Invariably loss of conscious, coma and death with several jerky and convulsive movements if poisoned animals are not attended with in a with in 1 hour after the appearance of clinical initial signs. Odour of the breath is ammonical/ bitter almond due to benzaldehyde production (often bloating, regurgitation is observed). Opening of rumen during post-mortem examination impart similar odour. Animals suspected for HCN poisoning must be differentiated from nitrite and other sr milar agents before initiating antidote therapy . In addition to antidotes, per oral administration of Cobalt chloride(10 mg/kg)and glucose is also indicated.

5. Nitrate/Nitrite:Drought is one of the root causes of nitrite toxicity in cattle/buffaloes. Nitrates are reduced to nitrite in ruminates. Otherwise, pigs are most sensitive species for nitrate toxicity. Contamination of drinking water with sewage, several plants species


134

(Amarantus sps,Palak etc.), plants grown in highly acidic soil, water logging and rich nitrated fields / effluents zone, deep well water or pond water originated from leaching of top soil (after -nitrate fertilizer application) are some of the common source of nitrite poisonings. Water soaked/entry of moisture may also render paddy hays/ corn in to nitrite rich within 18-22 hours. Frequent application of fields with non-toxic weed killer 2,4-D and nitratic fertilizer favour accumulation of nitrtes in plants. Any forage that contains over 1.5% nitrate (expressed as pot. nitrite) is considered relatively unsafe for livestock and should be fed with extreme caution. Nitrite ions induce meth-haemoglobenaemia as well as marked vasodilatation. Clinical signs include cyanosis, staggering gait, muscular tremors, rapid pulse, dyspnoea and dilated pupil. Opisthotonus, polyurea, chocolate brown colour of the blood and cyanotic mucous membranes are the characteristic features of nitrite toxicity. Untreated animals die with out a struggle. Reducing agents like Methylene blue or Ascorbic acid are the antidotes (see table 2 for details). Mineral oil or mucilaginous substances and diluted vinegar (4-5 lt. in cold water, per os) must be administered to counter GI irritation and further reduction of nitrates in the rumen respectively. Cardiovascular support (vasoconstrictor); and stimulants to counter prostration.

6. Poisonous plants: Toxicities/ death due to ingestion of poisonous plants are also often being the etiology of poisoning in the farm animals. Commonly with plant poisonings there are perplexing epidemiological features. For example, animal already grazing in the dangerous field are often unaffected while recently introduced may be poisoned. Drought, starved, ailing from pica, hungry, ravenous animals, curiously excited animals (often do not eat), and young animals less discriminate plants with different texture (attraction). Poisonous plants often show geographical limitations in their distribution, particularly industrial enterprises may create ‘poison hazard’ in local areas (Ipomea carnea, Amaranthus spinosus) and certain agricultural practices / soil type may also pose toxicities (eg. Nitrite, Selenium). Severe drought followed by rain/moisture/humid atmosphere favour accumulation nitrite in many plants. Similarly re-emergence of fresh leaves following harvesting also contains dangerous levels of HCN.

Essentially the source of plant poisoning can be classified into: a. naturally occurring b. Commercial crops/byproducts and c. Conventional and non-conventional fodders. Immature sorghum, maize, flax (linseed); Manihot esculenta (tapioca) newly emerging bamboo shoots and rubber leaves are the common source of HCN poisonings. Accidental ingestion of castor bean, rotten beat roots, adult nicotine leaves,Mimosa invisa (used to increase nitrogen fixation in soil) may become fatal.. Plants or foliage belonging to Brassicaceae sps.(Cruciferae) family i.e kale, rape,turnip, cabbage,reddish plants and


134

mustard seeds or meal may elicit severe toxicities in animals when fed /ingested large quantity due to the presence of glucosinolates in such plants..Digestive disturbance(enteritis),goiter polioencephalomalacia (rape blindness), pulmonary emphysema are the sequelae. Bloat, photosensitization is also observed. Affected animals are to be treated symptomatically.

Feeding of urea treated straws in excess/or fed to un-acclimatized animals may lead to urea poisoning, long term feeding of subabul may lead to hypothyrodism and feeding of fungus infested straws (sorghum, paddy or leguminous fodders) may pose threat of mycotoxicosis when fed relatively for a long period. Ficus tsjhela (Karnataka-Kerala boarder, Western Ghats); Acccia leucopholea (HCN), Amaranthus spinosus (nitrite); Jatropa curcus (purging nut); Crotalaria juncia (hepatotoxic pyrrolizidine alkaloids: monocrotaline);Flax(linseed, HCN); Ipomea carnea (LSD alkaloid like effects, also source of nitrite and cause photosensitization). Strychnous nux-vomica (coastal Karnataka); Abrus precatorius (Gulaganji); marking nut, Calitropis gigantica (yakka), croton oil and Yellow oleander are also some of the plant source of accidental poisonings and/or recorded in case of malicious poisoning in animals.

Antidotes and supportive treatments for common poisonings in large animals

Poison/toxicity Antidote/ treatment Dosage and method of treatment

Hydrocyanic acid (HCN) /Cyanide

Sodium nitrite followed by Sodium thiosulfate

Administer 1% sodium nitrite @ 15-25mg/kg,i.v followed by 25% sodium thiosulphate @ 1.25gm , slow i.v Na nitrite + Na thiosulfateCattle: 3gm + 15gm in 20ml water, s.c; Sheep/goats: 2gm+5gm in 15ml water,s.c. Cobalt chloride @10.2 mg/kg, per os; Approx. 4 lt. vinegar in 10-20lt. cold water; A large dose of vitamin B12 and anticonvulsants, if necessary. Give cobalt chloride 10mg/kg per-orally. Fluid therapy with dextrose-saline is ideal

Nitrate/nitrite Methylene blue

Or

Ascorbic acid

1% Methylene blue @ 8.8mg/kg, i.v and repeat 30 min later and if necessary administer at 6-8hr. interval Broad spectrum antibiotics intra-ruminally; Administer 8-10L cold


134

water and give osmotic purgatives Treat for hypotension/shock, (vasoconstrictors like 1:1000, 0.5 ml adrenaline, slow iv); Blood transfusion, if possible

Heavy metals

(Arsenic,antimony, mercury)

Arsenic/Mercurial insecticides)

Arsenic poisoning

British anti-Lewisite(BAL)

d-penicillamine

BAL: 3mg/kg as 5% mixture of 10% benzyl benzoate in mineral oil. Give deep i.m injection every 4hr. on first two days, every 6hr. on third day and then b.i.d for next 10 days. In cattle and horse sodium thiosulfate can also be used @ 8-10gram in the form of 10-20%solution (i.v) or 20-30gram per-orally in 300ml water.

Fluid therapy and other supportive treatment as required. Administer @ 30-40mg ,i..v + 60-80mg/kg; P.O, b.i.d or t.i.d for 3-4 days

Urea No antidote

Reduce the rumen pH

Administer 20-30lt. water and drench 4-6lt. 5 % acetic acid ; Anticonvulsants, if required

Strychnine

(Strychnous- nux vomica)

Phenobarbital sodium

Chloral hydrate

Phenobarbitone sodium,30mg/kg,i.v

Chloral hydrate @ 5g/45 kg, i.v

Drench tannic acid and then purgative

Rest the animal in cool, noise free & in dark room after a dose of purgative

Lead Calcium disodium EDTA Make 6.6% solution and administer @ 73 mg/kg,i.v (repeat or two treatment daily for 3 days if required). Combined thrapy with thiamine HCl @2-4mg/kg/day, s.c is more effective, Anticonvulsants, if required

Warfarine Vitamin- K1 Vitamin-K1: 300-500mg, S.C,every 4-6hr.Blood transfusion transfusion @ 20ml/kg or plasma @ 9ml/kg body wt;


134

Bromodiolone Sedatives/tranquilizer

Pyrethroids

(Deltamethrin,

Cypermethrin etc.)

No specific antidote, but

Diazepam HCl + Atropine SO4

Diazepam: 0.5-2 mg/kg, i.vAtropine SO4 as required

Activated charcoal (1-2kg), P.O Fluid therapy

Carbamate insecticides Atropine sulphate 0.25mg-0.5mg/kg,give ¼ intravenously and remaining ¾ by intra-muscular or sub-cutaneous route

Organophosphates Atropine sulphate +

2-PAM

Or

DAM(diacetyl -monoxime)

Atropinization: 0.25mg-0.5mg/kg,give ¼ i.v,remaining ¾ by i.m or s.c for every 3-6 hours. Observe for papillary dilatation and recovery symptoms and continue treatment as required.

2-PAM: 20%solution @ 25-50mg/kg,i.v or intra-muscualrly, Activated charcoal,P.O

Fluid therapy and supportive care

Organochorines ( D.D.T;, B.H.C & endosulphan etc.,)

Pentobarbitone sodium Or Chloral hydrate

30mg/kg,i.v and supportive care

5g/45 kg ,i.v and supportive care

Dinitro-herbicides (Dinitro-orthocresol-DNOC & Dinitrophenol-DNP)

In ruminants only: Treat for Methaemoglobinemia with methylene blue

Or

Ascorbic acid

Methylene blue: 2-4%,8-10mg/kg,i.v every 8hr. Or Ascorbic acid: 5-10mg/kg,i.v; every8hr. for first 24-48hr.Note: Do not give antipyretics to control hyperthermia. Administer saline purgatives. Fluid therapy with DNS

*****


134

CARE AND MANAGEMENT OF CRITICAL PATIENTS IN CLINICS

VIVEK.R.KASARALIKAR

Critically ill patient is special challenge to the clinician because the underline problem is not evident for about 24 to 48 hours after initial presentation. Expeditious therapy in right time can be life saving, whereas delayed adequate therapy may be ineffective therapeutic failure. Most common clinical conditions in ambulatory patients are trauma with internal/ external hemorrhage, poisoning and post surgical complication. In fact, specialized care of emergent patient begins with initial phone call from the owner and instructions to be given regarding first aid and transport procedures. Level of consciousness, breathing pattern and external hemorrhage should be enquired on priority.

The important first aid measures are:

Immobility and transport on firm flat surface Mouth to nose resuscitation in critical patient which is unconscious and not breathing

(Ten to twelve times per minute) Pulsating arterial bleeding is controlled by digital pressure and pressure bandage Penetrating foreign objects should be left in place till specialized help is available Head elevated by 200 in altered mental status after head or spinal injury

Evaluation and initial treatment: Three important assessment criterion in emergency patients are A, B and C by evaluating certain parameters .

A – Airway: Airway patency should be evaluated on priority. Noisy breathing without need of stethoscope suggests Large airway problem e.g. trachea and bronchus, whereas, inspiratory dyspnoea implies extra-thoracic airway compromise. Loud expiratory sounds reflect towards pathology of intra-thoracic airway including bronchioles and lung parenchyma.

B – Breathing: Sequence of respiratory compromise is increased in respiratory rate initially, followed by change in respiratory pattern. Laboured open mouth breathing with development of cyanosis suggests significant compromised pulmonary function.

In both the above conditions, immediate Oxygen administration is the priority. Intra-nasal catheter is the best choice for compromised breathing patients, whereas slash tracheotomy


134

with endotracheal intubation is preferred in unconscious and apneic patients (Nasal Oxygen flow rate should be kept at 50 – 100 ml/kg/min).

C– Circulation: Hemodynamic and cellular changes that occur as a result of abnormality in circulation is referred as shock or peripheral circulatory failure.; is clinically classified in to four main categories.

Hypovolemic: occurs due to atleast 15-25 % t deficit in circulatory blood volume Cardiogenic shock: occurs due to failure of heart to pump requisite quantity of

blood in to circulation Distributive shock: due to impaired distribution of circulatory blood volume as a

result of peripheral vasodialatation Septic shock: This is endotoxin mediated shock

Therapeutic management of critically ill patient:

1. Cardio-pulmonary Resuscitation (CPR):Hallmarks of Cardio-pulmonary arrest are a) stage of apnea with cyanosis of visible mucous membranes b) absence of palpable pulse c) absence of heart sounds and d) dilatation of pupils

Guidelines for Cardio-pulmonary resuscitation

a) Positioning of animal:Lateral recumbency on small animal examination table is optimal position in small sized dogs (< 7 kgs), whereas dorsal recumbency is preferred for large sized dogs.

b) Resuscitation:Chest compression coupled with mouth to nose ventilation should be performed in patients in apneic stage.Compression rate should be 60 to 120 per minute and the compression – ventilation ratio should be 15:2. It means for every 15 compressions 2 cycles of ventilation should be performed.

2. Management of shock: Assessment of shock is governed by these parameters Pale to cyanotic mucous membranes Tachycardia with weak pulse Significant fall in Systolic blood pressure (Below 60 mm of Hg) Central Venous Pressure (CVP) less than 5 mm of H2O Elevated level of Blood lactate (> 80 mg/dl) Significant increase in Capillary Refill Time (CRT)

Therapeutic management: Emphasis should be given to

Fluid therapy:The main aim of fluid therapy is to restore circulation and improve the tissue perfusion. Choice between crystalloid and colloidal solutions should be


134

determined. Crystalloid supplements fluid along with electrolytes, whereas colloidal solutions expand the plasma volume.Commonly used colloidal solutions are: Dextran 70, Hexastarch,Gelatin polymers, Frozen plasma, Packed cell component. Commonly used crystalloids are: Normal Saline, Lactated Ringer’s solution, Dextrose Normal Saline, 7.5 % Normal saline and Hypertonic dextrose solution

Corticosteroids:Stabilization of cell membrane, blocking of arachidonic acid metabolism and gluconeogenesis are few important roles of corticosteroids in the treatment of shock Cyclo-oxygenase inhibitors:These decrease the prostaglandin synthesis and other vaso-active amines.Eg; Flunixin Meglumin( 0.25 mg/kg); Ketoprofen(0.5- 2.2 mg/kg) Antibiotic therapy in septic shock: Broad spectrum antibiotic therapy has additional advantage in endotoxin related shock. Anti-bacterials with synergistic action are also preferred in septic shock. III to IV generation ceophalosporin like cefoperazone, ceftrioxone and cefixim are frequently used in small animal practice. Control of hemorrhage and blood transfusion: Antifibrinolytic drugs are preferred to counteract extensive hemorrhage. PAMBA (Para amino methyl benzoic acid), EACA (Epsilon amino caproic acid) and Botropase have fast styptic activity Alpha Adrenergic agonist: These drugs help in improving cardiac output and thereby improve tissue perfusion. Dopamine used @ 5 – 10 µg/kg/min as constant infusion has positive ionotropic effect and increase the systolic pressure.

*****


134

MANAGEMENT OF TOXICITY OF COMMON HOUSEHOLD SUBSTANCES

U. SUNILCHANDRA

Household products being formulated as complex chemical mixtures with multiple active ingredients designed for specific applications may be hazardous to pets and children with accidental exposure.The common route of exposure of the household hazardous compounds may be dermal, oral, ocular or inhalational. Some of the important indoor substancse with higher toxic potentiality are described especially with reference to pets.

SOAPS AND DETERGENTS: This class include soaps,shampoos, spray cleaners, dishwash liquids , powders, laundry products, disinfectants, fabric softeners and sanitizers. Bath soaps and bar soaps usually have low toxic potential, causing mild gastroenteritis with vomition, on ingestion. Demulcents and diluents: milk , rinsing with water for dermal and ocular exposure; Induction of emesis if soap is non alkaline( noncorrosive), if there is no spontaneous vomition within thirty minutes of ingestion and, fluid and electrolyte therapy.

Nonionic detergents ( alkyl ethoxylate; sources: shampoos, dishwash detergents,laundry detergents) generally have low order of 125oxicoses125 and toxicity, being non corrosive. Anionic (alkyl sodium sulfonate, dioctyl sodium sulfosuccinate, sodium lauryl sulfate; sources: shampoos, dishwash detergents, laundry detergents) and cationic ( benzalkonium chloride, ,cetirimide; sources: fabric softeners, germicides, disinfectants, sanitizers) detergents (Quaternary ammonium compounds) are corrosive and highly toxic. Ethanol and isopropanol, often found in cationic detergents ;enhance gastrointestinal absorption and damaged skin favours percutaneous absorption.

Toxicity related clinical signs are vomition, diarrhoea, gastrointestinal discomfort, intravascular hemolysis in impaired liver condition, dermal irritation, corneal damage ; Oral-corrosive damage, salivation,muscle weakness, respiratory and CNS depression, seizures, collapse, comapredominantly seen with cationic detergents. Treatment involves dilution with milk, water, egg white, administering act.charcoal, saline cathartics, fluids, antibiotic, analgesics and thorough washing the skin with soap and water and eye lavage with isothermic isotonic saline for 20minutes.

CORROSIVES:. Acidic corrosive (Hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, sodium bisulfite) product examples are antirust compounds, toilet bowl


134

cleaners, automobile batteries, gun barrel cleaning fluid and swimming pool cleaning agents. Alkaline (sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonium hydroxide, potassium permanganate) product examples are drain cleaners, washing products, liquid cleansers and toilet bowl products. On dermal and ocular exposure: serious burns, extremely painful, corneal/conjuctival necrosis, perforation and opacity. On ingestion: corrosive burns of mucosal membranes ( milky white/ grey, turning to wrinkled black). Vocalization,depression,,panting, inability to swallow.haematemesis, abdominal pain, polydypsia, respiratory distress, shock, secondary pneumonia from aspiration of vapours, gastrointestinal bleeding, perforation and fistula are the other signs observed depending on the severity. Oral dilution with egg white , milk or water, skin and eyes thourghly flushed with copious water and sterile saline respectively; therapy for shock: IV fluids, steroids within 48 hours, which reduce the fibroblastic activity and inflammation, reduce the stricture from circumferential alkaline burns. Analgesics and antibiotics prophylactically in animals with perforations. Attempts to neutralize burns chemically(as exothermic reactions produce elevated local heat and thermal burns), gastric lavage, induction of emesis are contraindicated. . Charcoal is ineffective in binding to caustics.

DISINFECTANTS: found in cleanimg products include quaternary ammonium compounds, phenol, pine oil, bleaches, alcohols; are more toxic than soaps and detergent compounds

Phenols: highly reactive,corrosive contact poisons; denatures and precipitates cellular proteins of all contacting cells. nephrotoxic, hepatotoxic and neurotoxic; rapidly absorbed through ingestion, inhalation or skin. Cats are highly sensitive. Sources of phenolic compounds: flooring materials, coal tar, creosote, tar paper. It results in intense pain, areas of coagulative necrosis; treated by glycerol, polyethylene glycol washing, thorough rinsing with water , dressings soaked in 0.5% soda bica. Also may cause corrosive burns of mouth, oropharynx, oesophagus. Vomition, salivation,ataxia, panting, weakness, tremor, coma, seizures, methhaemoglobinaemia, respiratory alkalosis, severe liver and kidney damage. Demulcents-milk, egg white, gastric lavage and emesis(contraindicated if severe damage) activated charcoal, saline cathartic, 1% methylene blue, 4mg/kg;IV; ascorbic acid 20mg/kg,PO; N-acetyl cysteine 140mg/kgIV, 70mg/kg PO. Q,id for 3 days. Ocular exposure is treated by sterile saline wash.

Bleaches: preparations contain sodium hypochlorite.Calcium hypochlorite and trichloroisocyanuric acid are present in industrial strength bleaching solutions ,swimming pool chlorine products and chlorine laundry bleaches. Non chlorine bleach preparations or colorfast bleaches contain sodium peroxide, sodium perborate or enzymatic detergents.


134

Generally, the toxicity of bleaches is of lower degree, resulting in irritation of ropharynx, salivation, vomition and abdominal pain. Bleaching of hairs, pulmonary irritation- coughing , dyspnoea and retching on inhalation may also be seen. Nonchlorine bleach products, (sodium perborate, sodium peroxide) are alkaline and severe gastric irritatants causing renal damage and CNS excitation, depending on the amount ingested.

Treatment: Milk and water orally; washing with soap and rinsing with abundant water/sterile saline on dermal/ocular exposure. Induction of emesis and orogastric lavage is contraindicated to avoid the risk of causing further oesophageal irritation. Milk of magnesia (2-3ml/kg) can be administered and other clinical signs are treated symptomatically.

Deodorants: composed of aluminum chloride and aluminum chlorohydrate; which have moderate toxicity potential. Ingestion can cause oral irritation, necrosis, gastroenteritis and nephrosis.; which can be treated by orogastric lavage, antiemetics and gastroprotectant drugs.

SOLVENTS AND ALCOHOLS: The most commonly encountered solvent (acetone: sources: nail polish remover, varnishes, glues )and alcohols include isopropanol(perfumes,cologne, grooming products), methanol (antifreeze products, automotive wind shield clesnser, consumer products) and alcohol (alcoholic beverages, cosmetics, mouthwashes ,common baker’s and brewer’s yeast). Activated charcoal is ineffective in binding to the alcohols, not to be used. Clinical signs noticed are CNS and respiratory depression acidosis, ataxia, hypothermia, cardiac arrest, coma; which is treated by emesis induction, (if < 2 hrs); IV fluid Ringers lactate/ saline solution with NaHCO3(1-3mEq/kg). Ethanol reduce severity of methanol poisoning.

Petroleum distillates: The compounds include cyclohexane, alkanes and alkenes. Sources: gasoline (petrol), kerosene, motor fuels, solvent paints and vehicles for pesticides. Because of low surface tension, chance of aspiration is most common. Dermal exposure may result in dermatitis. Oral exposure results in aspiration pneumonia, cough, hyperthermia, cyanosis, CNS depression and pulmonary oedema.. Emetics and oily purgatives are contraindicated, as they increase the risk of aspiration. Gastric lavage and activated charcoal should be reserved for ingestion of large amount(2ml/kg) or when other toxicants are present. Oxygen therapy, rest , flushing the skin and eyes with water and IV fluids to maintain hydration and electrolyte balance is recommended. Other solvents (eg: acetone, turpentine) or other hydrocarbons should not be used for removing the petroleum distillates from skin.


134

BATTERIES : Automotive or dry cell batteries contain sulfuric acid, that can be irritating on contact with eyes, skin and gastrointestinal tract., which is treated accordingly as with acid exposure.The sources of small disc/button batteries include batteries used in calculators, cameras, hearing aids, watches , the content being mainly mercuric oxide. The dry cell batteries , commonly used in toy flash lights, may contain the alkaline ( NaOH, KOH; alkaline batteries) or acidic compounds (ammonium chloride, manganese dioxide, heavy metals- Li, Ni, Zn, Ag, Cd) in them. On ingestion, most of the intact batteries pass through digestive tract within 24 to 36 hours without producing any major adverse effects, except for mechanical obstruction occasionally. Gastrointestinal distress may occur resulting from retention and obstruction, which has to be diagnosed by radiography and has to be corrected by endoscopy and surgery . If battery is chewed and split apart, it may cause corrosive damage depending on the chemical content in it. Timely surgical intervention together with the administration of saline cathartics, enemas and appropriate chelation therapy with specific chelating agents if any (eg: DMSA or D-Penicillamine as for Pb), can minimize the corrosive damage caused. Lead is the major source of toxicity among the metals, resulting in acute or chronic toxicity upon ingestion. The sources of lead are paints, batteries, solder, plumbing supplies, lubricating material, ceramic containers, Pb pipes, toys, inks, dyes, used oil from vehicles that burn leaded gasoline. The clinical signs noticed are Acute- CNS excitability signs, convulsions, behavioural changes, ataxia, tremor, blindness. Chronic-gastrointestinal disturbance signs, vomition, pica,diarrhoea, abdominal pain. Treatment is by administering Ca disodium EDTA, 25mg/kg, q.i.d, SC diluted in 10% dextrose ,Oral D-penicllamine, 110mg/kg/day, 1-2 weeks, Dimercaptosuccinic acid(DMSA), 10mg/kg,t.i.d.

CYANOACRYLATE ADHESIVES ( SUPERGLUE) : Uncured cyanoacrylate adhesives form an almost instantaneous bond on contact with hair/skin resulting in annoyance and frustration of the animal. Cured ones are nontoxic upon ingestion .Dermal exposed areas are soaked with warm soapy water as quickly as possible. and with acetone for several minutes, if area is away from face or eye. The hairs may be clipped to reduce the tension on skin. The surfaces should not be pulled apart, with direct opposing actions.Ocular : Eyelid/eyeball is thoroughly washed with warm water and Elizabeth collar is applied to prevent self trauma. The animal will be able to open eyes on its own with no residual tissue damage within 2-3 days and hence forceful manipulation should not be done.

Methylxanthines: Sources: Coffee, tea, chocolates, cola/soft drinks, asthma, analgesic,cold medications. Caffeine, 128oxicoses128is and theobromine are the primary


134

toxic agents. Clinical signs manifested by vomition, diarrhoea, polyuria, weakness, hyperexcitability, tremors, seizures, coma and death resulting from cardiac tachyarrhythmias. If ingestion is less than 2 hours, emetics administration followed by, activated charcoal and saline cathartic is indicated. Since methylxanthines undergo enterohepatic recycling, charcoal should be administered every 3-6 hours until symptoms disappear. Antiarrythmics (lidocaine, without epinephrine; 1-2mg/kg,IV- loading dose; 40-60mg/kg/min infusion rate, slow IV- as maintenance dose) or beta blocker (metoprolol; 0.1- 0.3mg/kg,PO,tid) to control arrhythmia;Diazepam or phenobarbitol to control seizures and fluid therapy to maintain hydration and electrolyte balance is recommended. Corticosteroids and erythromycin should be avoided as they decrease urinary excretion of methylxanthines.

Aspirin : Clinical signs of aspirin toxicoses in cats are dose-dependant and may include CNS depression, anorexia, vomiting, gastric hemorrhage, 129oxicoses129is , toxic hepatitis, anemia, bone marrow hypoplasia, hyerpnea and hyperpyrexia, hyperthermia, hyperglycemia, and glycosuria. Treatment is by GI decontamination with emetics, activated charcoal and cathartics, within 4 hours of ingestion. Acid-base imbalance is corrected with a slow infusion of sodium bicarbonate, carefully monitored and adjusted to avoid pulmonary edema being developed. The resulting hyperthermia should be controlled by external cooling; the use of antipyretic drugs should be avoided.

Paracetamol: Toxicity Signs: Dirty brown colored gums, dyspnoea, haematuria, jaundice ,facial and paw edema , cyanosis, hypothermia, and vomiting. Less common signs include coma, generalized weakness, and death. If ingestion is less than 2 hours, emetics, activated charcoal and saline or osmotic cathartic are indicated.. If severe cyanosis is present, oxygen therapy should administered, and the animal should be subject to as little stress as possible.IV Administration of acetylcysteine, 140mg/kg/hr for 7 hours; Ascorbic acid, 30 mg/kg orally to reduce methemoglobinemia to Hb. Supportive care including fluid therapy for possible metabolic acidosis is also recommended.The other drugs used for NSAID 129oxicoses include ranitidine(2mg/kg,tid,IV,PO),omeprazole(0.7mg/kg,sid,PO),metoclopramide(0.2-0.4mg/kg, tid,PO,IM), sucralfate (0.5-1g, bid,PO)and misoprostol(2-5µg/kg,tid,PO)

Xylitol: is a sweetener used in sugar free products/chewing gums;induces hypoglycaemia by stimulating insulin secretion , resulting in weakness,m ataxia, seizures and collapse. Therapy: Inducing emesis administering activated charcoal, 50% dextroseIV and liver tonics


134

Amitraz: poisoning occurs commonly from ingestion of a tick collar. Clinical signs include ataxia, bradycardia, CNS depression, vomition, diarrhoea, and seizures. Treatment involves decontamination (emesis, activated charcoal, saline cathartic) and repeated injections of yohimbine (0.1mg/kg.IV) or atepamizole to reverse its adrenergic agonistic effects and atropine has to be avoided as it may increase the absorption.

*****


134

MANAGEMENT OF MYCOTOXINS AND ZOOTOXINS OF VETERINARY IMPORTANCE

M.VIJAY KUMAR

Mycotoxins are the toxic metabolites released by moulds under certain conditions conducive for their growth. Acute or chronic toxicoses can result from exposure to feed or bedding contaminated with toxins that may be produced during growth of various saprophytic or phytopathogenic fungi or molds on cereals, hay, straw, pastures, or any other fodder. The principles that characterize mycotoxic diseases: the cause may not be immediately identified; they are not transmissible from one animal to another; treatment with drugs or antibiotics has little effect on the course of the disease; outbreaks are usually seasonal because particular climatic sequences may favor fungal growth and toxin production and study indicates specific association with a particular feed.

There are various types of mycotoxins and are classified as follows. Based on the causative organism: Aflatoxins - Aspergillus flavus, A. parasiticus.;Rubratoxins - Penicillium rubrum, P.purpurogenum.; T-2 toxins - Fusarium sp. F.gramaenareum and F. roseum.; Ergotoxins – Claviceps purpurea and C. paspali.Among these most common are aflatoxins. Aspergillus moulds grow rapidly when the moisture is <15%and the temperature is 24-25ºC.They commonly affect GNC, CSC, coconut cake, sunflower cake, wheat, sorghum, millets, soybean, peas and almonds.

Susceptibility:Ducks, rabbits, dogs, pigs, calves, chicken, cows, quail and sheep are susceptible in the order of preference. Broilers are more susceptible than layers. Calves are more susceptible than adult dairy cattle. Maximum allowable conc. in dairy cattle is 20 ppb (0.02 ppm)Depending on fluorescence aflatoxins are classified into B1, B2, and G1, G2. B1 is most toxic and need to be converted into its active metabolites.Toxicity is through ingestion of aflatoxin-contaminated feed. Aflatoxins are not accumulated to any appreciable extent by animal tissues with the exception of milk.

Signs:Acute - sudden death or anorexia, depression, dyspnoea, coughing, nasal discharge, anaemia, epistaxis, bloody faeces, possible convulsions and death. Subacute - jaundice, hypoprothrombinemia, haematomas and haemorrhagic enteritis. Chronic - decreased feed efficiency, decreased productivity and weight gain, rough hair coat, anaemia, enlarged abdomen, mild jaundice, depression and anorexia. Abortions may occur.


134

Postmortem Lesions: Wide spread heamorhages,Icterus,Gastroenteritis,Hepatic necrosis,Massive centrilobular necrosis,fibrosis of bile duct,Enlarged liver,Hydrothorax, Ascites,Oedema of Gall bladder wall,Pericellular cirrhosis

Diagnosis: based on History,Clinical signs,PM findings,Detection of Aflatoxin M1 in milk & urine,liver, kidney,Serum liver enzymes SGOT,SGPT,ALP elevated,Reduced prothrombin activity,Hyperbilerubinemia,Tlc,HPLC,RIA,ELISA

Differential diagnosis: Warfarin (haemorrhages), coal tar (mottling of liver) Copper poisoning (haemoglobinuria, hemolysis); Pyrrozolidine alkaloids (present in plants), CCl4, blue-green algae, crotalaria are hepatotoxic.Treatment: 1. Avoidance of contaminated feed. 2. Hydrated sodium calcium alumino silicate (HSCAS) adsorb aflatoxins @5kg /ton 3. Stanozolol (2 mg / kg) I/M decreases hepatic necrosis 4. Oxytetracycline (10mg / kg) I/M decreases hepatic necrosis.( Never administer oxytetracycline and stanzolol combination, they are mutually antagonistic) 5. Activated charcoal 6.7 mg / Kg I/R as 30% W/V slurry in M/15, PH 7 PBS(Along with charcoal,stanzolol/oxytetracycline(any one) ) 6. GSH Precursors Cysteine,methionine @2.2mg/kgi/p 7. Multi vitamins Like E,K & Selenium 8. Feeding easily digestible and low fat diet containing adequate protein

Sample collection : Samples can be taken at various stages:growing crops or during transport or storage. Whenever possible, samples should be taken after particulate size has been reduced (Ex: by shelling or grinding) and soon after blending has occurred (as in harvesting, loading, or grinding).Most effective if small samples are taken at periodic, predetermined intervals from a moving stream of grain or feed. These individual stream samples should be combined and mixed thoroughly, after which a subsample of 10 lb (4.5 kg) should be taken.. A suggested method of probe sampling is to sample at 5 locations, each 1 ft (30 cm) from the periphery of a bin, plus once in the center. This should be done for each 6 ft (2 m) of bin depth. Thus, taller bins would require more samples, and the total weight should be >10kg.

Dry samples are preferable for transport and storage. Samples should be dried at 176-194°F (80-90°C) for > 3 hr to reduce moisture to 12-13%. If mold studies are to be done, drying at 140°F (60°C) for 6-12 hr should preserve fungal activity.Containers should be appropriate for the nature of the sample. For dried samples, paper or cloth bags are recommended. Plastic bags should be avoided unless grain is dried thoroughly. Plastic bags are useful for high-moisture samples only if refrigeration, freezing, or chemicals are used to retard mold growth during transport and storage. Once a sample has been cooled or frozen, warming may induce condensation and allow mold growth.


134

Zootoxins :Out of 236 species of snakes in India, only 50 are venomous, However, the common poisonous snakes of India that man and animal come into contact, are : Cobra, Krait, Russel’s viper and Sea scaled viper, Apart from these, the other venomous snakes found in India includes Sea snakes, Pit viper and King cobra.. In animals, many a time incidence of snakes bite is near leg region and nostrils.

Sensitivity: Horse>Man>Sheep>Cattle>Goat>Dog>Pig>Cat

Venom composition: The venom compositions vary significantly among various class of poisonous snakes. Therefore, the course of toxicity as well as well as cause of death will be different, and obviously therapeutic approach will also vary. On most occasions, the identification of snake is not available or doubtful. The nature of toxicity of poisonous snakes are: Elapidae: Cobra , King Cobra, Krait- Neurotioxic; Viparidae: Russel viper- Haemotoxic; Crotalidae: Pit Viper- Neutrotoxic Haemotoxic. All the bites from venomous snakes do not lead to death due to “dry bites” which means that no venom was injected. But, some snake venoms (krait) do not have immediate effect even in a bad bite, it is wise to give veterinary/medical care.

Cobra:. identified by their “defence display” by spreading their long bones to their famous hood. ; are most active at dust, having along the wedges of agricultural fields in search of rats/mice. For this reason they live mostly in cultivated area.. The cobra venom is rich in enzymes, cardiotoxic, neurotoxic factors. The cobra venom is rich in enzyme acetylcholinesterase. Therefore, rapid depletion of acetylcholine (ACh) at neuromuscular junction occurs following envenomation. This leads to “muscular paralysis” (flacid paralysis). In addition to it, the alpha-neurotoxin is a powerful cholinoceptor blocker (nicotinic receptors). These factors hinder the function of muscles involved in respiration and consequently death occurs due to “respiratory paralysis”. It is important to identify the “big four” dangerous snakes. At first sight cobra looks like a non-venomous rat snake, but, remember that the rat snake has a pointed head and larger eyes and it can run faster.

Krait: The common krait has bluish-bluck body with white cross bands and the head is short and blunt. Kraits venom is 10 times as powerful as that of the cobra and of all the Asian snakes its venom is the most toxic (neurotoxic). Kraits are noctoural. They are active at night and rest during the day. They are found throughout India and live mostly in sandy soil in rat burrows. Their favarite hiding places are piles of wood (on bricks which provide many pray to shelter in. They are canibalistic- eat snakes, rats, lizards and birds. Famale lays eggs (10-15) and stays with them until hatch.


134

Russel viper: is a fat and bulky snake, but it can move with surprising speed when in danger. Its regular chain-like pattern and flat arrow shaped head make it easy to recognise. Its fangs are along and curved.. Venom is rich in proteolytic enzymes, hemolytic factors.

Pit vipers: are forest snakes and feed on frogs and lizards. Commonly found in coffee and tea plantations in India. Pit vipes have a small “pits” between nostrils and eyes. They are heat sensitive and can detect change in temperature when warm blooded animal comes near. Venom is not powerful and seldom results in death.

First-Aid treatment: The first aim, in case of cobra/krait bite is to retard the absorption of venom from the site of bite. ;done by applying a torniquet, provided site of bite is suitable for that. Do not disturb/ or/excite the animal with little care incise the area (1/4) and bleed. It is always better to avoid KMnO4 solution for wound wash and instead use 5% soap wash in 30 min. after bite. It is not advisible to apply torniquet in case of vipers bite as this venom is rich in spreading factors (local tissue necrosis).

Hospital treatment: The nature of hospital treatment practically depends on identity of the poisonous snake. Polyvalent antivenin is the drug of choce in the absence of identity. It is better to avoid administration of antihistaminic as they are found to increase toxic potential of certain vipers venom. Popularly, hospital treatment can be remembered as “AAA”: A = Antivenin.; A = Antibiotic (broad spectrum) andA = Antitetanus / Gas gnagrene antitoxins.

The antivenin (monovalent/polyvalent) should be administered IV at the rate of 100 ml. (small animals) or 10-50ml. (large animals). Administer antivenom with 1:00 epinephrine (0.5-1 ml. s/c) to avoid shock. Apply 1-2ml. of antivenin over the wound (site of bite in case of viper bite. Monitor the cardio vascular activity constantly. Narcotic analeptic is recommended in case of cobra bite to counteract intense pain. Epinephrine and corticosteroid to overcome hypotension and shock. Employ plasma volume expander (6% dextran-40) and calcium gluconate to reduce hemolysis. In case of viper bite, even if the patient survive, amputation may be performed to avoid spread of local tissued necrosis or gangrene formation.

Note: - Anitivenom should be stored at 40C. Do not administer if they are discoloured or after the date of expiry.

*****


134

A BRIEF NOTE ON ANTIDOTES OF VETERINARY IMPORTANCE

U.SUNILCHANDRA

Acepromazine maleate: (Acetyl-promazine): Indicated in seizures associated with amphetamine methamphetamine, 4-Methylimidazole, metaldehyde poisoning,usually preceding use ofbarbiturate or other anticonvulsant. Contraindicated in organophosphate or strychnine poisoning Dose: Dogs, Cats-0.03-0.05 mg/kg IV, IM;Swine-0.1-0.2 mg/kg IV, IM;Cattle, Horses- 0.02-0.1 mg/kg IV, IM;Sheep-0.03-0.05 IV; Goats 0.03-0.1 mg/kg

Acetic acid (Dilute 4%-6%)/ : Indicated in Ammonia toxicosis; urea, carbon monoxide, hydrogen sulfide, and opiate, metallic salts; arsenic, selenium, tin, thallium, antimony Sheep, Goats-0.5-1 L/ animal/ PO Cattle, Sheep,Goats- 5-7 ml/kg of a dilute solution 1:4 or 1:5 with water or 20% DextrosePO

Aminophylline/ Theophylline: Respiratory stimulants, used in benzodiazepine type poisonings: flurazepam, midazolam, forazepam. Dose: Horse- 4-15 mg/kg PO, IV; q8-12h Dogs- 4-10 mg/kg PO, IV; q8-12h

Amyl Nitrite/ Isoamyl Nitrite/ Isopentyl Nitrite/: indicated in cyanide, hydrogensulfide, acrylonitrile,chloroform, iodine,nitrates and strychnine poisonings. Cattle,Horse -30-60 minute inhalation; Dogs- 1.5-5 minute inhalation

Activated Charcoal: (10%): Carbon absorbent which absorbs toxic substancesand irritants, non-specific organics Not effectivefor minerals (elemental,acids, salts, alkalis), nor oils. Cattle, Sheep, Goats-1.0-3.0 g/kg PO; Horses-0.5-1.65 g/kg PO; Dogs,Cats -2-8 g/kg PO

Atipamezole HCL: Indicated in medetomidine, xylazine,amitraz, midodrine, and phenylepherine overdose poisoning and Dogs- 50 mcg/kg IM q3-4h . Yohimbine HCl is alpha adrenergic antagonist with weak monamineoxidase (MAO) inhibition. Used in the treatment of drug overdose and poisoning: Amitraz, Xylazine, Clonidine.

Ascorbic acid(Vitamin C): indicated for drugs, plants and metal poisonings; copper,iron, selenium,chromium,cobalt,lead,arsenic,nitrate-nitrite,chlorates,aniline, hydrazine,hydroquinones, benzocaine, phenacetin, potassium permanganate, quinines, toluidine,sulfonamides, acetaminophen, ,Johnson Grass(Sorghum), Feed Grain plants that have been stressed with drought or herbicide and thereby accumulate nitrates. Cattle,


134

Horses - 7.5-15 mg/kgIV,IM,SQ,PO;Dogs,Cat10-25mg/kgIV,IM,,PO;Rabbits, Rodents100mg/kgIV,IM,SQ,PO;

Swine,Sheep-5-10mg/kgIV,IM,SQ,PO;Goats-2.5-5mg/kgIV,IM,SQ,PO.

Atropine Sulfate (dl-Hyoscyamine): Indicated in Poisonings: carbamate and organophosphate pesticides:Aldicarb,Fumarate,Bromophos,Carbaryl,Chlofenvinphos,Chlorpyrifos,Diazinon,Dicrotophos,Dioxathion,Disulfaton,Fensulfothion,Fenthion,Malathion,Methidathion,Methiocarb,Methomyl, Parathion,Profenphos, Propoxur,Terbufos, Tetraethyl, pyrophosphate, Sarin, Soman, Tabun, Paraxon, Tacrine HCL,Baclofen, Bethanechol chloride, Bisprolol, Chloroform, Nicotine,Mushroom,Carbolic Acid, Phenol,Benzene,physostigmine,Nitrobenzene, Cyanides,Opium, Morphine, as well as to treat poisoning associated bradycardia,hypotension. Dose: Cattle, Horse,Dog, Cat, Swine,Sheep, Goats, Birds,Reptiles, Rabbits, Rodent -0.1-2.0 mg/kg administer ¼ dose IV ;with the remainder SQ or IM

Calcium gluconate/ Calcium borogluconate: (Calcium chloride; Calcium lactate) : Indicated in hypocalcemia and cardiac dysrhythmias associated with hyperkalemia: Lead, Fluoride, Carbon tetrachloride, Ethylene glycol, Oxalic acid, Chlorinated hydrocarbons, Hydrogen fluoride, Hydrofluric acid, Calcium channel blockers (Nifedipine,Diltiazem),Phosphine, Hypermagnesemia, Oxalates. Dose: Ca gluconate: Cattle, Horses, Sheep,Goats, Swine -150-250 mg/lg IVslowly, PO; Dogs, Cats 25-150 mg/kg IV slowly PO; Birds 50-100 mg/kg IV slowly ,PO Ca chloride: Cattle,Horses25-125 mg/kg IV slowly PO; Sheep,Goats20-30 mg/kg IV slow,PO; Swine- 20-60 mg/kg IV ,Dogs, Cats 5-50 mg/kg IV slow; Ca lactate: cattle, Horses, Goat, Sheep- 40-250 mg/kg PO ; Swine-40-500 mg/kg PO PRN; Dogs, Cats-30-150 mg/kg PO

Diazepam/ Methyl Diazepam: Anticonvulsant and Anxiolytic, indicated in the treatment of seizures that may be caused bydirect toxic effects or secondary to hypoxia or other metabolic or electrolyte disturbance; Isoniazid, Lithium, Salicylates, Theophylline,Caffine, Theobromine, Amphetamines, Nicotine, Atropine, Aminopyridine,Lead, Metaldehyde, Cyanides, Fluoroacetate,Mycotoxins,Organochlorines,Organophosphates,Carbamates,TricyclicAntidepressants,Strychnine, Cocaine, Opioids, Mefenamic Acid, Methylxanthines, Phenylethylamines, Ergot Alkaloids . Dose: Cattle, Sheep,Goats -0.5-2.0 mg/kg IV, IM; Horses -0.5-50.0 mg/kg IV, IM ; Swine- 0.5-10.0 mg/kg IV, IM; Dogs- 0.5-5.0 mg/kg IV, IM; Cats-0.5-2.5mg/kg IV, IM; Rabbits- 0.5-10.0 mg/kg IV, IM; Birds -0.5-2.0 mg/kg IV, IM


134

Egg white: Natural clear colloidal protein (albumin) mass;denatures, coagulates, and is heat sensitive, has good demulcentproperties. Indicated in thetreatment of mercury,copper, tin, silver,hydrogen peroxide,phenol, picric acid,formaldehyde, ether,alcohol, household cleaners and detergents, corrosive chemical poisonings. Dose: Dogs, Cats, Calves, Foals, Lambs,Kids, Pigs11-2 egg whites/5-10 kg PO; Usually administered with milk

Epinephrine/ Adrenaline: Positive inotrope,cardiovascular stimulantand bronchodilator. Usedin the treatment of insect bite-induced anaphylaxis,insect bite poisoning, drug-inducedanaphylaxis, drugpoisoning; beta-blocker poisoning, chloroquine,vaccines, ants, Bees or honey bees. Dose: Cattle,Horses, Sheep, Goats, Swine, Dogs, Cats 0.01-0.02 mg/kg (0.45-0.9 ml 1:1,000/kg) IM,SQ; 0.01-0.02 mg/kg (1:10,000) IV.

Gelatin : Heterogeneous mixture of water-soluble proteins derived from natural collagen; absorbent (absorbs 5-10 times its weight), demulcent, stabilizer, thickener, texureizer, and hemostatic sponge. Used in the treatment of household chemical poisoning; aqueous cleaners, bases and alkalis.Dose: Dogs,Cats, Foals, Lambs,Kids, Pigs. (2 tablsp/5-10 kg)3-6 g/kg PO

Sodium Nitrite: Used inconjunction with Amyl Nitrite and Sodium Thiosulfate in the treatment of Cyanide,Hydrogen Sulfide and other poisonings: Cattle, Horses- 4.5-7.5 mg /kg IV, IP; Sheep, Goats- 10 mg/kg IV, IP; Dogs, Cats 16-22 mg/kg IV, IP Always used in combination with Sodium Thiosulfate

Sodium thiosulfate: Used in the treatment of cyanide and some metal poisonings: Cisplatin, Iodine, Arsenic, Chlorates, Cyanide, Eucalyptus (Eucalyptus), Acacia, Cherry, Plum,, Sorghumand Johnsongrass (Sorghum), Contraindicated for Hydrogen Sulfide. Dose: Cattle,Horses- 15-25 mg/kg IV, IP as25% solution; Cattle, Horses- 8.5-13.2 mg/kg IV, IP as 25% solution when administered with or following Sodium Nitrite; Sheep,Goats-20-60 mg/kg IV, IP as 25% solution; 10-30 mg/kg IV, IP as 25% solution when administered with or following Sodium Nitrite; Swine- 10-20 mg/kg as 25%; Dogs -50-200 mg/kg as 25% sol.

Sodium Bicarbonate/ Baking Soda : Short-acting, potent antacid. Systemic alkalinizer , used to correct metabolic acidosis and to alkalinize urine in poisonings and drug overdose: Amitriptyline-Perphenazine, Amitryptyline, Doxepin, Ethylene Glycol, Formaldehyde, Glycol Ethers,Imipramine, Metformin, Methanol, Nortriptyline, Potassium Chloride, Propylene Glycol, Quinidine, Strychnine, Trimipramine Maleate,


134

Ethanol, Salicylates, Chlorphenoxy Herbicides, Jimmyweed and Goldenrod (Isocoma), Sugar Beet (Beta)Dose should be equivalent to ½ of calculated dose administered by slow intravenous infusion. Cattle-70-180 mg/kg PO ; Horses-40-120 mg/kg PO; Sheep, Goats-20-100 mg/kg PO ; Dogs-20-80 mg/kg PO ; Cats-20-150 mg/kg PO.

Phytonadione/Phylloquinone/Phytomenadione (Vitamin K1): promotes liver biosynthesis and regeneration of clotting factors . Will not reverse the anticoagulant effects of heparin. Used in the treatment of hypoprothrombinemia caused by drug overdose, chemical, rodenticide and plant poisonings: Coumarin, Indandione, Quinidine, Quinine, Salicylates, Sulfonamides, Brodifacoum, Bromadiolone, Chlorphacinone, Hydroxycoumarin, Indanedione, Pindone, Dicumarol, Warfarin, sweet Clover (Melilotus),Dose: Cattle, Horses, Sheep, Goats, Swine, Birds- 0.5-2.5 mg/kg SQ, IMdaily; Dogs, Cats -2-5 mg/kg PO, SQ, IM daily in divided dose

Dimercaprol: Chelator of metal ions which form soluble sulfhydral group-ion complexes that areeliminated in the urine; used for the treatment of gold, cobalt, antimony,Contraindicated in Cadmium poisoning,arsenic (except arsine), copper, mercury,bismuth, hromium,nickle, tungsten, zinc,and methyl bromide poisoning. and much less effective in lead, selenium and thallium poisoning Dose: Cattle, Horses, Sheep,Goats, Swine, Dogs,Cats- 1-2 mg/kg IM qid;Contraindicated in Cadmium poisoning,

Neostigmine: competitive inhibitor of acetylcholinesterase. Used in the treatment of non-depolarizing neuromuscular blocking agents. treatment of curare, atropine, ivermectin, avermectins,tubocurarine, gallamine, atracurium, pancuronium , botulism (Cl. Botulinum), and as a secondary agent in the treatment of Coral and Cobra (Naja) snake bite and Tetrodotoxin poisoning from Porcupine Fish, Deadly Nightshade Atropa), Jimson Weed (Datura), Henbane (Hyoscyamus), Mandrake (Mandragora), Jasmine .Dose: Dogs- 0.001-0.05 mg/kg SQ, IM; Cats-0.01-0.04 mg/kg IM; Cattle, Horses- 0.02-0.4 mg/kg SQ, IV; Swine-0.03-0.06 mg/kg IM; Sheep, Goats-0.01-0.03 mg/kg SQ;Corticosteroids may decrease effects.

*****


134

FORENSIC REGULATIONS-A DISCUSSIONPSI

BIDAR RURAL POLICE STATION

The following is a brief acts and sections that are commonly used at the site of crime pertaining to the veterolegal cases commonly.

THE INDIAN PENAL CODE[Act, No. 45 of 1860]1

[6th October, 1860]Chapter: 1 – INTRODUCTIONSection 1 - Title and extent of operation of the Code Section 2 - Punishment of offences committed within India Section 3 - Punishment of offences committed beyond, but which by law may be tried within, India Section 4 - Extension of Code to extra-territorial offences Section 5 - Certain laws not to be affected by this Act Chapter: 2 - GENERAL EXPLANATIONSSection 6 - Definitions in the Code to be understood subject to exceptions Section 7 - Sense of expression once explained Section 8 - Gender Section 9 - Number Section 10 - "Man", "Woman" Section 11 - "Person" Section 12 - "Public" Section 13 - "Queen" [Repealed]Section 14 - "Servant of Government" Section 16 - "Government of India" [Repealed] Section 17 - "Government" Section 18 - "India" Section 19 - "Judge" Section 20 - "Court of Justice" Section 21 - "Public Servant" Section 23 - "Wrongful gain" Section 24 - "Dishonestly" Section 25 - "Fraudulently" Section 26 - "Reason to believe" Section 27 - Property in possession of wife, clerk or servant Section 28 - "Counterfeit" Section 29 - "Document" Section 29A - "Electronic record" Section 30 - "Valuable security"


134

Section 32 - Words referring to acts include illegal omissions Section 33 - "Act", "Omission" Section 34 - Acts done by several persons in furtherance of common intention Section 35 - When such an act is criminal by reason of its being done with a criminal knowledge or intention Section 36 - Effect caused partly by act and partly by omission Section 37 - Co-operation by doing one of several acts constituting an offence Section 38 - Persons concerned in criminal act may be guilty of different offences Section 39 - "Voluntarily" Section 40 - "Offence" Section 41 - "Special law" Section 42 - "Local law" Section 43 - "Illegal", "Legally bound to do" Section 44 - "Injury" Section 45 - "Life" Section 46 - "Death" Section 47 - "Animal" The word "animal" denotes any living creature, other than a human being.Section 49 - "Year", "Month" Section 50 - "Section" Section 51 - "Oath" Section 52 - "Good faith" Section 52A - "Harbour" Chapter: 3 - OF PUNISHMENTSSection 53 - Punishments Section 53A - Construction of reference to transportation Section 54 - Commutation of sentence of death Section 55 - Commutation of sentence of imprisonment for life Section 55A - Definition of "appropriate Government" Section 57 - Fractions of terms of punishment Section 58 - Offenders sentenced to transportation how dealt with until transported [Repealed] Section 59 - Transportation instead of imprisonment [Repealed] Section 60 - Sentence may be (in certain cases of imprisonment) wholly or partly rigorous or simple Section 61 - Sentence of forfeiture of property [Repealed] Section 62 - Forfeiture of property in respect of offenders punishable with death, transportation or imprisonment [Repealed] Section 63 - Amount of fine Section 64 - Sentence of imprisonment for non-payment of fine Section 65 - Limit to imprisonment for non-payment of fine, when imprisonment and fine awardable Section 66 - Description of imprisonment for non-payment of fine


134

Section 67 - Imprisonment for non-payment of fine, when offence punishable with fine only Section 68 - Imprisonment to terminate on payment of fine Section 69 - Termination of imprisonment on payment of proportional part of fine Section 70 - Fine leviable within six years, or during imprisonment-- Death not to discharge property from liability Section 71 - Limit of punishment of offence made up of several offences Section 72 - Punishment of person guilty of one of several offences, the judgment stating that it is doubtful of which Section 73 - Solitary confinement Section 74 - Limit of solitary confinement Section 75 - Enhanced punishment for certain offences under Chapter XII or Chapter XVII after previous conviction Chapter: 4 - GENERAL EXCEPTIONSSection 76 - Act done by a person bound, or by mistake of fact believing himself bound, by law Section 77 - Act of Judge when acting judicially Section 78 - Act done pursuant to the judgment or order of Court Section 79 - Act done by a person justified, or by mistake of fact believing himself justified, by law Section 80 - Accident in doing a lawful act Section 81 - Act likely to cause harm, but done without criminal intent, and to prevent other harm Section 82 - Act of a child under seven years of age Section 83 - Act of a child above seven and under twelve of immature understanding Section 84 - Act of a person of unsound mind Section 85 - Act of a person incapable of judgment by reason of intoxication caused against his will Section 86 - Offence requiring a particular intent or knowledge committed by one who is intoxicated Section 87 - Act not intended and not known to be likely to cause death or grievous hurt, done by consent Section 88 - Act not intended to cause death, done by consent in good faith for person's benefit Section 89 - Act done in good faith for benefit of child or insane person, by or by consent of guardian Section 90 - Consent known to be given under fear or misconception Section 91 - Exclusion of acts which are offences independently of harm caused Section 92 - Act done in good faith for benefit of a person without consent Section 93 - Communication made in good faith Section 94 - Act to which a person is compelled by threats Section 95 - Act causing slight harm Section 96 to 106 - Of the Right of Private Defence


134

Section 96 - Things done in private defence Section 97 - Right of private defence of the body and of property Section 98 - Right of private defence against the act of a person of unsound mind, etc. Section 99 - Acts against which there is no right of private defence Section 100 - When the right of private defence of the body extends to causing death Section 101 - When such right extends to causing any harm other than death Section 102 - Commencement and continuance of the right of private defence of the body Section 103 - When the right of private defence of property extends to causing death Section 104 - When such right extends to causing any harm other than death Section 105 - Commencement and continuance of the right of private defence of property Section 106 - Right of private defence against deadly assault when there is risk of harm to innocent person

Chapter: 5 - OF ABETMENTSection 107 - Abetment of a thing Section 108 - Abettor Section 108A - Abetment in India of offences outside India Section 109 - Punishment of abetment if the act abetted is committed in consequence, and where no express provision is made for its punishment Section 110 - Punishment of abetment if person abetted does act with different intention from that of abettor Section 111 - Liability of abettor when one act abetted and different act done Section 112 - Abettor when liable to cumulative punishment for act abetted and for act done Section 113 - Liability of abettor for an effect caused by the act abetted different from that intended by the abettor Section 114 - Abettor present when offence is committed Section 115 - Abetment of offence punishable with death or imprisonment for life--if offence not committed Section 116 - Abetment of offence punishable with imprisonment--if offence be not committed Section 117 - Abetting commission of offence by the public or by more than ten persons Section 118 - Concealing design to commit offence punishable with death or imprisonment for life Section 119 - Public servant concealing design to commit offence which it is his duty to prevent Section 120 - Concealing design to commit offence punishable with imprisonment

Chapter: 9 - OF OFFENCES BY OR RELATING TO PUBLIC SERVANTSSection 161 - [Repealed] Section 162 - [Repealed] Section 163 - [Repealed] Section 164 - [Repealed]


134

Section 165 - [Repealed] Section 165A - [Repealed] Section 166 - Public servant disobeying law, with intent to cause injury to any person Section 167 - Public servant framing an incorrect document with intent to cause injury Section 168 - Public servant unlawfully engaging in trade Section 169 - Public servant unlawfully buying or bidding for property Section 170 - Personating a public servant Section 171 - Wearing garb or carrying token used by public servant with fraudulent intent Chapter: 10 - OF CONTEMPTS OF THE LAWFUL AUTHORITY OF PUBLIC SERVANTSSection 172 - Absconding to avoid service of summons or other proceeding Section 173 - Preventing service of summons or other proceeding, or preventing publication thereof Section 174 - Non-attendance in obedience to an order from public servant Section 175 - Omission to produce document or electronic record to public servant by person legally bound to produce it Section 176 - Omission to give notice or information to public servant by person legally bound to give it Section 177 - Furnishing false information Section 178 - Refusing oath or affirmation when duly required by public servant to make it Section 179 - Refusing to answer public servant authorised to question Section 180 - Refusing to sign statement Section 181 - False statement on oath or affirmation to public servant or person authorised to administer an oath or affirmation Section 182 - False information, with intent to cause public servant to use his lawful power to the injury of another person Section 183 - Resistance to the taking of property by the lawful authority of a public servant Section 184 - Obstructing sale of property offered for sale by authority of public servant Section 185 - Illegal purchase or bid for property offered for sale by authority of public servant Section 186 - Obstructing public servant in discharge of public functions Section 187 - Omission to assist public servant when bound by law to give assistance Section 188 - Disobedience to order duly promulgated by public servant Section 189 - Threat of injury to public servant Section 190 - Threat of injury to induce person to refrain from applying for protection to public servant Chapter: 11 - OF FALSE EVIDENCE AND OFFENCES AGAINST PUBLIC JUSTICESection 191 - Giving false evidence Section 192 - Fabricating false evidence Section 193 - Punishment for false evidence


134

Section 194 - Giving or fabricating false evidence with intent to procure conviction of capital offence Section 195 - Giving or fabricating false evidence with intent to procure conviction of offence punishable with imprisonment for life or imprisonment Section 195A - Threatening or inducing any person to give false evidence Section 196 - Using evidence known to be false Section 197 - Issuing or signing false certificate Section 198 - Using as true a certificate known to be false Section 199 - False statement made in declaration which is by law receivable as evidence Section 200 - Using as true such declaration knowing it to be false Section 201 - Causing disappearance of evidence of offence, or giving false information to screen offender Section 202 - Intentional omission to give information of offence by person bound to inform Section 203 - Giving false information respecting an offence committed Section 204 - Destruction of document or electronic record to prevent its production as evidence Section 205 - False personation for purpose of act or proceeding in suit or prosecution Section 206 - Fraudulent removal or concealment of property to prevent its seizure as forfeited or in execution Section 207 - Fraudulent claim to property to prevent its seizure as forfeited or in execution Section 208 - Fraudulently suffering decree for sum not due Section 209 - Dishonestly making false claim in Court Section 210 - Fraudulently obtaining decree for sum not due Section 211 - False charge of offence made with intent to injure Section 212 - Harbouring offender Section 213 - Taking gift, etc., to screen an offender from punishment Section 214 - Offering gift or restoration of property in consideration of screening offender Section 215 - Taking gift to help to recover stolen property, etc. Section 216 - Harbouring offender who has escaped from custody or whose apprehension has been ordered Section 216A - Penalty for harbouring robbers or dacoits Section 216B - Definition of "harbour" in sections 212, 216 and 216A Section 217 - Public servant disobeying direction of law with intent to save person from punishment or property from forfeiture Section 218 - Public servant framing incorrect record or writing with intent to save person from punishment or property from forfeiture Section 219 - Public servant in judicial proceeding corruptly making report, etc., contrary to law Section 220 - Commitment for trial or confinement by person having authority who knows that he is acting contrary to law


134

Section 221 - Intentional omission to apprehend on the part of public servant bound to apprehend Section 222 - Intentional omission to apprehend on the part of public servant bound to apprehend person under sentence or lawfully committed Section 223 - Escape from confinement or custody negligently suffered by public servant Section 224 - Resistance or obstruction by a person to his lawful apprehension Section 225 - Resistance or obstruction to lawful apprehension of another person Section 225A - Omission to apprehend, or sufferance of escape, on part of public servant, in cases not otherwise, provided for Section 225B - Resistance or obstruction to lawful apprehension, or escape or rescue in cases not otherwise provided for Section 226 - Unlawful return from transportation [Repealed] Section 227 - Violation of condition of remission of punishment Section 228 - Intentional insult or interruption to public servant sitting in judicial proceeding Section 228A - Disclosure of identity of the victim of certain offences etc. Section 229 - Personation of a juror or assessor

Chapter: 14 - OF OFFENCES AFFECTING THE PUBLIC HEALTH, SAFETY, CONVENIENCE, DECENCY AND MORALS

Section 268 - Public nuisance Section 269 - Negligent act likely to spread infection of disease dangerous to life Section 270 - Malignant act likely to spread infection of disease dangerous to life Section 271 - Disobedience to quarantine rule Section 272 - Adulteration of food or drink intended for sale Section 273 - Sale of noxious food or drink Section 274 - Adulteration of drugs Section 275 - Sale of adulterated drugs Section 276 - Sale of drug as a different drug or preparation Section 277 - Fouling water of public spring or reservoir Section 278 - Making atmosphere noxious to health Section 279 - Rash driving or riding on a public way Section 280 - Rash navigation of vessel Section 281 - Exhibition of false light, mark or buoy Section 282 - Conveying person by water for hire in unsafe or overloaded vessel Section 283 - Danger or obstruction in public way or line of navigation Section 284 - Negligent conduct with respect to poisonous substance Section 285 - Negligent conduct with respect to fire or combustible matter Section 286 - Negligent conduct with respect to explosive substance Section 287 - Negligent conduct with respect to machinery Section 288 - Negligent conduct with respect to pulling down or repairing buildings Section 289 - Negligent conduct with respect to animal


134

Whoever knowingly or negligently omits to take such order with any animal in his possession as is sufficient to guard against any probable danger to human life, or any probable danger of grievous hurt from such animal, shall be punished with imprisonment of either description for a term which may extend to six months, or with fine which may extend to one thousand rupees, or with both.

Section 290 - Punishment for public nuisance in cases not otherwise provided for Section 291 - Continuance of nuisance after injunction to discontinue Section 292 - Sale, etc., of obscene books, etc. Section 293 - Sale, etc., of obscene objects to young person Section 294 - Obscene acts and songs Section 294A - Keeping lottery office

Chapter: 16 - OF OFFENCES AFFECTING THE HUMAN BODYSection 299 to 311 - Of Offences Affecting Life Section 299 - Culpable homicide Section 300 - Murder Section 301 - Culpable homicide by causing death of person other than person whose death was intended Section 302 - Punishment for murder Section 303 - Punishment for murder by life-convict Section 304 - Punishment for culpable homicide not amounting to murder Section 304A - Causing death by negligence Section 304B - Dowry death Section 305 - Abetment of suicide of child or insane person Section 306 - Abetment of suicide Section 307 - Attempt to murder Section 308 - Attempt to commit culpable homicide Section 309 - Attempt to commit suicide Section 310 - Thug Section 311 - Punishment Section 312 to 318 - Of the Causing of Miscarriage, of Injuries to Unborn Children, of the Exposure of Infants, and of the Concealment of Births Section 312 - Causing miscarriage Section 313 - Causing miscarriage without woman's consent Section 314 - Death caused by act done with intent to cause miscarriage Section 315 - Act done with intent to prevent child being born alive or to cause it to die after birth Section 316 - Causing death of quick unborn child by act amounting to culpable homicide Section 317 - Exposure and abandonment of child under twelve years, by parent or person having care of it Section 318 - Concealment of birth by secret disposal of dead body Section 319 to 338 - Of Hurt


134

Section 319 - Hurt Section 320 - Grievous hurt Section 321 - Voluntarily causing hurt Section 322 - Voluntarily causing grievous hurt Section 323 - Punishment for voluntarily causing hurt Section 324 - Voluntarily causing hurt by dangerous weapons or means Section 325 - Punishment for voluntarily causing grievous hurt Section 326 - Voluntarily causing grievous hurt by dangerous weapons or means Section 327 - Voluntarily causing hurt to extort property, or to constrain to an illegal act Section 328 - Causing hurt by means of poison, etc. with intent to commit an offence Section 329 - Voluntarily causing grievous hurt to extort property, or to constrain to an illegal act Section 330 - Voluntarily causing hurt to extort confession, or to compel restoration of property Section 331 - Voluntarily causing grievous hurt to extort confession, or to compel restoration of property Section 332 - Voluntarily causing hurt to deter public servant from his duty Section 333 - Voluntarily causing grievous hurt to deter public servant from his duty Section 334 - Voluntarily causing hurt on provocation Section 335 - Voluntarily causing grievous hurt on provocation Section 336 - Act endangering life or personal safety of others Section 337 - Causing hurt by act endangering life or personal safety of others Section 338 - Causing grievous hurt by act endangering life or personal safety of others Section 339 to 348 - Of Wrongful Restraint and Wrongful Confinement Section 339 - Wrongful restraint Section 340 - Wrongful confinement Section 341 - Punishment for wrongful restraint Section 342 - Punishment for wrongful confinement Section 343 - Wrongful confinement for three or more days Section 344 - Wrongful confinement for ten or more days Section 345 - Wrongful confinement of person for whose liberation writ has been issued Section 346 - Wrongful confinement in secret Section 347 - Wrongful confinement to extort property, or constrain to illegal act Section 348 - Wrongful confinement to extort confession, or compel restoration of property Section 349 to 358 - Of Criminal Force and Assault Section 349 - Force Section 350 - Criminal force Section 351 - Assault Section 352 - Punishment for assault or criminal force otherwise than on grave provocation Section 353 - Assault or criminal force to deter public servant form discharge of his duty


134

Section 356 - Assault or criminal force in attempt to commit theft of property carried by a person Section 357 - Assault or criminal force in attempt wrongfully to confine a person Section 358 - Assault or criminal force on grave provocation Section 359 to 374 - Of Kidnapping, Abduction, Slavery and Forced Labour Section 359 - Kidnapping Section 360 - Kidnapping from India Section 361 - Kidnapping from lawful guardianship Section 362 - Abduction Section 363 - Punishment for kidnapping STATE AMENDMENTSSection 363A - Kidnapping or maiming a minor for purposes of begging Section 364 - Kidnapping or abducting in order to murder Section 364A - Kidnapping for ransom, etc. Section 365 - Kidnapping or abducting with intent secretly and wrongfully to confine person Section 366 - Kidnapping, abducting or inducing woman to compel her marriage, etc. Section 366A - Procuration of minor girl Section 366B - Importation of girl from foreign country Section 367 - Kidnapping or abducting in order to subject person to grievous hurt, slavery, etc. Section 368 - Wrongfully concealing or keeping in confinement, kidnapped or abducted person Section 369 - Kidnapping or abducting child under ten years with intent to steal from its person Section 370 - Buying or disposing of any person as a slave Section 371 - Habitual dealing in slaves Section 372 - Selling minor for purposes of prostitution, etc. Section 373 - Buying minor for purposes of prostitution, etc. Section 374 - Unlawful compulsory labour Section 375 to 376D - Sexual Offence Section 375 - Rape Section 376 - Punishment for rape Section 376A - Intercourse by a man with his wife during separation Section 376B - Intercourse by public servant with woman in his custody Section 376C - Intercourse by superintendent of jail, remand home, etc. Section 376D - Intercourse by any member of the management or staff of a hospital with any woman in that hospital Section 377 - Of Unnatural Offences : Unnatural offences Section 420 - Cheating and dishonestly inducing delivery of property Section 421 to 424 - of fraudulent deeds and dispositions of property Section 421 - Dishonest or fraudulent removal or concealment of property to prevent distribution among creditors Section 422 - Dishonestly or fraudulently preventing debt being available for creditors


134

Section 423 - Dishonest or fraudulent execution of deed of transfer containing false statement of consideration Section 424 - Dishonest or fraudulent removal or concealment of property Section 425 to 440 - Of mischief Section 425 - Mischief Section 426 - Punishment for mischief Section 427 - Mischief causing damage to the amount of fifty rupees Section 428 - Mischief by killing or maiming animal of the value of ten rupees

Whoever commits mischief by killing, poisoning, maiming or rendering useless any animal or animals of the value of ten rupees or upwards, shall be punished with imprisonment of either description for a term which may extend to two years, or with fine, or with both.

Section 429 - Mischief by killing or maiming cattle, etc., of any value or any animal of the value of fifty rupees

Whoever commits mischief by killing, poisoning, maiming or rendering useless, any elephant, camel, horse, mule, buffalo, bull, cow or ox, whatever may be the value thereof, or any other animal of the value of fifty rupees or upwards, shall be punished with imprisonment of either description for a term which may extend to five years, or with fine, or with both.

Section 430 - Mischief by injury to works of irrigation or by wrongfully diverting water Whoever commits mischief by doing any act which causes, or which he knows to be likely to cause, a diminution of the supply of water for agricultural purposes, or for food or drink for human beings or for animals which are property, or for cleanliness or for carrying on any manufacture, shall be punished with imprisonment of either description for a term which may extend to five years, or with fine, or with both.


134

DIAGNOSTIC TESTS FOR DETECTION OF COMMON TOXICANTS

M.VIJAY KUMAR

Detection of Heavy metals: Place 10g of tissue (finely minced) in a beaker or test tube.Add 10 ml of 10% HCl.Introduce a copper wire into the test tube Boil for 10-15 min. (Do not inhale fumes) Remove the copper wire and place it on a filter paper Observe the colour of the copper wire. Inference: Black coloration - Arsenic or Bismuth; Shining silver deposit – Mercury; Dull white deposit – Silver; Dark colour with purple to blue; violet green - Antimony.

Depending on the colour of copper wire the confirmatory test is conducted.If the deposit is black it can be confirmed whether it is due to arsenic or bismuth by placing the copper strip in 1-2 ml. of 10 % potassium cyanide. If the deposit is due to arsenic, it will dissolve, but if it is due to bismuth or antimony, it will persist.In mercury, colour of the deposit ranges grayish (50 mg) to shiny silver (100 mg).

Detection of lead: Mince the liver/kidney piece or collect a small amount of scraping from stomach wall.Add a few drops of conc. nitric acid and heat gently till dry, (never over heat the sample as it turns black making reading difficult). Add a few drops of water and two drops of 10% pot. iodide solution.Development of yellow colour indicates presence of lead.

Detection of Cyanide:

a) in biological material: Take 50 g of finely ground tissue or stomach contents in a 100 ml flask and acidify thecontents with tartaric acid. Take a filter paper previously moistened with 10 % of guaiacol in alcohol and 0.1% of aqueous copper sulfate solution.Plug the mouth of flask and warm gently. Allow it to stand for 30 minutes. Observe the colour of paper. If cyanide is present, a blue colour develops.

b) in the plant sample: Preparation of sodium picrate paper-Dissolve sodium bicarbonate 5 g and picric acid 0.5 g in 100 ml of distilled water. Cut filter paper into strips of 2. x 6. size. Dip the strips in the reagent and dry in cool place.

Take the given sample in a test tube and add a few drops of water and chlorofom. Plug the test tube with cotton, hanging the dried picrate paper inside the test tube. The paper


134

should not touch the fluid in the tube. Heat the tube gently till fumes evolve. Observe the colour of paper.If the colour of paper changes from yellow to brown it indicates that the plant sampleis positive for cyanide.(The leaves and stomach contents are to be frozen immediately after collection inpolythene bag as CN is likely to evaporate).

Detection of fluorides: To a small quantity (1-3 ml) of urine or stomach contents add 3 ml of sodium hydroxide solution in a glass or porcelain dish. Add a little quantity of powdered glass and mix thoroughly. Apply moderate heat till dry. Add 10 ml of concentrated sulfuric acid and cover the dish with a small plate from the under surface of which is suspended a drop of 5% sodium chloride solution. Place a small piece of ice on top of the plate to prevent evaporation of the drop. Heat gently for 3-5 min., carefully remove the drop and examine under low power of microscope. If the given specimen contains fluorides, silicon fluoride is formed which appears as small light pink hexagonal crystals along the rim of the drop, whereas the crystals of sodium chloride are large and square.

Detection of Nitrite:

a) Draw blood (10 ml) without anticoagulant from an affected animal and also from a known normal animal in 20 ml capacity test tubes.Place them in boiling water bath for 45 minutes. Cool them.Observe the colour of the blood and the surface.Blood sample containing nitrite is Salmon pink in colour, does not pull away fromthe side and the surface is level or concave. Normal blood sample is chocolate brown,pulls away from the side of tube and the surface is convex.

c) In a plant sample: Dissolve 0.5 g of diphenylamine in 20 ml of distilled water and make up the volume to 100 ml with sulfuric acid. Store it in amber colored bottle. This is a full strength solution and can be made into half strength by diluting with equal parts of 80% sulfuric acid. To test a plant, place a drop of the reagent on the cut surface of plant. Observe the colour.A green to blue colour indicates the presence of nitrate.(A green to blue colour with a half strength solution indicates positive (++) for nitrate, which could be toxic to animal).

*****


134


134

RATIONAL USE OF HORMONES IN ANIMAL REPRODUCTION

M.K.TANDLE

The following is a brief description of various harmones used in animal reproductive disorders

1. Oxytocin: The effect of oxytocin on uterus is to change the weak, spontaneous and irregular contractions. Physiologically oxytocin has shorter half-life (about 2 minutes) due to its cleavage in plasma by oxytocinase. Therapeutic response to oxytocin is always better when administered as slow intravenous drip rather than given as a single bolus dose. The binding of oxytocin to specific receptors present in mammary gland and myometrium.stimulates smooth muscle contractions promoting uterine motility and milk let down. The efficacy of exogenously administered oxytocin is more in estrogen-sensitized uterus and the response to oxytocin is greatest when circulatory estrogen levels are high.

Indications: Induction of parturition ( only in case of sufficient cervical dilation), expulsion of last fetus in polytocous animal, post caesarian section- to speed up involution and control bleeding after removal of fetus , as local infiltration, expulsion of placental debris, uterine inertia and post repositioned uterine prolapse ( to reduce enlargement and facilitate contraction ).Dosage : Mare 75-125 IU ; Cow 75-100 IU ;Sow, Ewe 30-50 IU ;Bitch 5-25 IU;cat 5-10 IU. Route IM or IV

Precautions: Generally oxytocin preparations contain sodium sulfite as a preservative therefore it should not be infused with solutions containing higher concentration of dextrose to overcome possible drug interaction. Administration of oxytocin in dystocia without sufficient cervical dilation is contraindicated. Intravenous administration may be done by diluting oxytocin with distilled water in 1:10 ratio.Products: Inj. Pitocin (Parke –Davis) 5 IU / 0.5 ml , Inj. Syntocinon (Novartis) 5 IU / ml

2. Prostaglandins :

a. Cloprostenol sodium (PGF2 α analogue) : It has potent luteolytic action that brings about regression of corpus luteum (CL) and induces fertile estrus following luteolysis.


134

Indications: Cow, buffalo: sub estrum, luteal cyst, synchronized breeding, removal of mummified fetus, chronic endometritis, pyometra and induction of parturition

Dosage: IM, IV, SC; Cattle, Buffalo: 2 ml IM, SC; 1.3 ml IV. Contra indicated in pregnancy except for termination of pregnancy.Keep away from pregnant woman veterinarian, persons suffering with asthma or other diseases of respiratory tract Products: Inj. Juramate 263 µg / ml,2 ml (Vetcare); Inj. Synchromate 263 µg / ml, 4 ml (Prima Vetcare), Inj Cyclix, Intervet, 2 mL and 20 mL vials ; Inj Clostenol, Sarabhai Zydus. 2 mL

b. Luprostiol (PGF2α analogue) -Dosage: Cow 15 mg, heifer and Horse 7.5 mg;Products: Inj. Prosolvin 7.5 mg / ml 2 ml, 10 ml, 20 ml (Intervet)

c. Tiaprost (PGF2α analogue)-Products: Inj. Iliren 0.196 mg / ml, 10 ml (Intervet); Dosage:Bovine 3.5 ml IV, 5 ml SC IM, Equine 3 ml IV, Caprine 1-1.5 ml SC

d. Dinoprost (PGF2 α analogue) : Dosage: Pyometra, chronic endometritis: Cattle 5 ml IM’; Induction of parturition: Cattle 3.5 ml IV, Horse 3 ml IM, Pig 2-4 ml IM; MTP: Cattle 3.5 ml IV .Products : Inj. Hormo P2α 5 mg / ml, 5 ml(BCAHP) ; Inj. Lutalyse 5 mg / ml10 ml (Novartis)

3. Estrogens: Natural estrogens include oestradiol, estrone and oestriols. They have low bioavailability following postoperative administration. Simple esters of steroidal estrogens such as benzoates or valerate are used in therapeutics as they release parent molecule on hydrolysis. Potency of estrogen is enhanced adding ethinyl groups to the molecule.

Indications: Misalliance, urinary incontinence in old, spayed bitches, uterine infections, anal adenoma and to induce estrus in bitches. Dosage: Dog 1-3 mg daily orally / 0.5 – 1 ml, IM. Precautions: Polydypsia, polyuria, GI upsets, suppression of red cell production,

chronic use may lead to hypogonadism and cystic ovary in females. Products:TabEvalon,30s (Infar); TabProgynon-C30’s ;Inj. Progynon Depot 1 ml amp. (German

Remedies)

4. Conjugated estrogens: To prevent conception in small animal (misalliance) as it delays transport of zygote from oviduct into the uterus. In uterine infections, estrogens facilitate uterine drainage through cervix provided cervix is dilated.

Indications: Misalliance (within one week following breeding), urinary incontinence in spayed / old bitches, anal adenoma, lactation, suppression and uterine infections . Precaution: Pregnancy, feminization in male and large doses may cause aplastic anemia.


134

Products: Premarin (Wyeth lederle) Dosage: Dog, Cat 3 tabs daily for 3 days, 1 ml IM , Tab 0.625 mg; Inj. 25 mg / ml)

II. Hormones used to treat reproductive disorders :The choice of hormones and drugs acting on reproductive system are important as therapeutic agents during reproductive disorders like anoestrus, metritis, pyometra, repeat breeder, retention of fetal membranes, delayed puberty, ovarian disorders etc. The dosage, route, frequency and indications of hormones acting on reproductive system are mentioned in tabular form as below.

Note: Trade names mentioned by the authors are only examples and in any form the author is not promoting or recommending any pharmaceutical products for treatment.

Particulars Indications Dosage and

route in cow

and buffalo

Commercial preparations

DRUGS ACTING ON FEMALE GENITAL SYSTEM-OVARIES

Buserelin-GnRH analogue stimulates follicular development, estrus and ovulation by enhancing release of FSH and LH

Anoestrus,

Delayed ovulation

2.5 mL, IM, IV Inj Receptal, Intervet

0.0042 mg/mL,

10 mL vialTrueanoestrus,Follicular cyst

5mL, IM, IV

Gonadorelin-GnRH analogue

stimulates follicular development, estrus and ovulation by enhancing release of FSH and LH

Cystic ovarian disease 100 mcg IM, IV Inj Cystorelin, BCAHP,50 mcg/ml,

2 mL, 10 mL vialsDelayed ovulation,Repeat breeder,Improvement of post partum fertility

250 mcg IM, IV

PITUITARY GONADOTROPINS

Follicle Superovulation in ETT 50 mg BID for 4 Inj Folltropin-V,


134

stimulating hormone

FSH induces folliculogenesis in mature female ovaries

days Vetrepharm Inc400 mg/vial + 20 mL diluent

Luteinizing hormone

induces maturation, estrogen production and finally ovulation of Graafian follicles and also the growth of CL

Anovulation

Delayed ovulation

Cystic ovaries,Repeat breeding

25 mg, IV Inj Lutropin-V, Vetrepharm Inc,25 mg vial + 5 mL diluent

NON-PITUITARY GONADOTROPHINS

Human chorionic gonadotrophin

mimics the effect of pituitary LH causing ovulation. It promotes the formation and maintenance of CL

Repeat breeding 1500-3000 IU, IM Inj Chorulon, Intervet,1500 IU vial

Inj Coriogan, Intervet,250 IU/mL

1000 IU, 2000 IU vials

Inj Corion,Win Medicare,1000 IU,

2000 IU, 5000 IU vials

Cystic ovaries 1500-3000 IU, IV

Delayed ovulation 1500-3000 IU, IM repeat on day 8

Post partum lactation failure 1500-3000 IU, IM , q 24 h with synthetic oxytocin

Early abortion 1500-3000 IU / week for 4 weeks as IM

Pregnant mare serum gonadotrophin (FSH like action) induce follicular growth in inactive ovaries of mature animals

Superovulation in ETT 1500-3000 IU

IM, IV

Inj Folligon, Intervet1000 IU vl; Inj Synchro part 400, 500, 600, 700, 6000 IU,BCAHP

Other combinations

To improve quality and yield of superovulation in ETT n bovines

Day 1, 6 mL BID ;Day 2, 5 mL BID;Day 3, 3 mL

Inj Ovaset, BCAHP


134

FSH 0.48 mg/9 mL, LH 0.42 mg/3mL

BID;Day 4, 2 mL BID

9 mL vial FSH + 3 mL vial LH +12 mL diluent

hCG 3000 IU, Progesterone 125mg/ vial

Cystic ovarian syndrome 1 vial as slow IV Inj Nymfalon, Intervet;hCG 3000 IU, Progesterone 125 mg/ vial

Ovarian steroids

Hydroxy-Progesterone caproate

Stimulates luteal action and cause quieting of myometrium, enhances endometrial glandular secretions, thus favour in maintenance of pregnancy. At lower doses it induces ovulation by its indirect effects on LH release

Delayed ovulation,Post partum anoestrus

500 mg, IM Inj Duraprogen, Unichem;Inj Proluton Depot, German Remedies

Inj Uniprogestin Depot, Foreva;Inj Vetaprogen, Prima Vet care;Inj P-Depot, Sarabhai Zydus;Inj Dinolutin, ;Alved250 mg/ mL, 2 mL ampoule

Cystic ovarian disease 500 mg, IM

Habitual abortion (late) 500 mg for 3 days followed by 500 mg/week, IM

Habitual abortions (early) 500 mg after 11/2 monthpregnancy, repeat every 10 days, IM

Progestagen Norgestomet- Synthetic Progestagen

Administered as ear implant to control/induce/ synchronize ovulation in normal healthy animals. In conjunction with estradiol act as a strong negative feed back complex

Control/ induce/synchronize ovulation in normal healthy animals

3 mg implant SC on ear (to be kept for 9 days) + 2 mL Inj IM

Crestar implant, Intervet

(Norgestomet 3 mg + (estradiol valerate 5 mg, Norgestomet 3 mg) per mL)

6 mg implant SC on ear (to be kept for 9

Synchromate-B implant, BCAHP


134

on hypothalamic hypophyseal system preventing final growth and maturation of follicles. Sudden withdrawal of Progestagen releasing implant lead to an increase of LH pulse frequency resulting in estrus and ovulation within 2-3 days

days) + 2 mL Inj IM

(Norgestomet 6 mg + (estradiol valerate 5 mg, Norgestomet 3 mg) per mL)

Prostaglandins

Dinoprost- PGF2α analogue

Potent luteolytic action by constriction of utero-ovarian vessels. It enhances cervical dilation and also has selective spasmogenic action.

Sub-estrum

Luteal cyst

Timing and synchronization of estrus

5 mL, IM Inj Hormo P2α, BCAHP5mg/mL,

5 mL vial;Inj Lutalyse, Novartis5mg/mL, 10 mL vial

Luprostiol- PGF2α analogue

It causes regression of CL followed by follicle growth, estrus and ovulation in sub-estrus and anoestrus.

Sub-estrus,Anoestrus,

Luteal cystPersistent CL,Estrus synchronization

15 mg, IM Inj Prosolvin, Intervet.7.5mg/mL,2 mL, 10 mL,

20 mL vials

Tiaprost- PGF2α analogue

Luteolytic activity; enhances cervical

Sub-estrus,Luteal cyst

Estrus synchronization

3.5 mL, IV or

5 mL SC/IM

Inj Iliren, Intervet

0.196 mg/mL, 10 mL vial


134

dilation and has selective spasmogenic action.

Estrogens

Natural steroidal estrogens- estradiol, estrone, estriols. Low oral activity, Potency is enhanced adding Ethinyl groups to the molecules

Induction of estrus

Induction of parturition,Pyometra,RFM

1.5 mL on day1 and 1.5 mL after 3

3 mL

Inj Progynon Depot, Zydus Cadila,1 mL amp,Inj Heatreg ,(di-ethyl stilboestrol 10 mg/mL), Novitech ,3 mL ampoule

Hydroxy Progesterone caproate

Progesterone acts on the endometrium inhibiting myometrial activity and thus quieting uterus

Pre partum uterine/ vaginal prolapse

500 mg,alternate days for 3 times, IM

Inj Duraprogen, Unichem

Inj Proluton Depot, German Remedies

Inj Uniprogestin Depot, Foreva

Inj Vetaprogen, Prima Vet care

Inj P-Depot,

Zydus AHL

250 mg/ mL,

2 mL ampoule

Post partum prolapse 500 mg for 3 days ; 500 mg/week for 3 weeks, IM

Prolapse due to pronounced heat

500 mg for 2 days, repeat on 3rd day, IM

Habitual pronounced heat 500 mg at the beginning of estrus, IM

Miscellaneous drugs / products

Eazi Breed CIDR Post partum and suckling anoestrus

Cystic ovaries

Silent estrus

Estrus synchronization

Inserted for 7 days;

Inserted for 12 days

Inserted for 10 days along with estradiol benzoate cap 10 mg or insert for 7 days

Eazi Breed CIDR, Saideep,

10,s


134

and administer PGF2α on 6th day or at the time of removal

*****


134


134

ANTIMICROBIAL THERAPY WITH MACROLIDES AND LINCOSAMIDES

U.SUNILCHANDRA

Macrolides and lincosamides are antibacterials mainly employed in therapy of respiratory infections and infections due to intracellular organisms and opportunistic pathogens.

MACROLIDES:The macrolides (macrocyclic lactones)are bacteriostatic,(bactericidal at high concentrations.) interfering with bacterial protein synthesis by reversibly binding to the 50 S ribosomal subunit. In general, they have a spectrum similar to that of the penicillins and are often used as penicillin substitutes for the treatment of streptococcal and staphylococcal infections.In addition,they are active against Mycoplasmae, Chlamydiae, Legionellae, Rickettsia spp. gram positive anaerobes etc.. They enter pleural, ascitic fluids but not the CSF. The important agents are erythromycin, oleandomycin, spiramycin, josamycin, tylosin, tilmicosin and newer ones: azithromycin,dirithromycin, clarithromycin and roxithromycin The newer agents are effective in opportunistic infections associated with toxoplasmosis, cryptosporidiosis etc, and also in the eradication of H.pylori infection

Side Effects and Toxicity: Gastrointestinal disturbances: are the most common adverse effect noticed. Vomiting, diarrhoea, anorexia, regurgitation and epigastric pain may be observed .Horses are sensitive to macrolide-induced GI disturbances that can be serious and even fatal. Some salts: Erythromycin estolate may be hepatotoxic and cause cholestasis;

Hypersensitivity reactions occasionally been seen. Clinical signs include rashes, fever, skin eruptions. Pain and swelling at the injection site . In pigs, tylosin may cause edema of the rectal mucosa, mild anal protrusion with diarrhea, and anal erythema and pruritus. Tylosin and Tilmicosin have a tendency to produce cardiac toxicity characterized by tachycardia and decreased contractility. Tilmicosin is contraindicated in swine and should not be used IV. Transcient auditory (hearing)impairments and super infections in humans are the other unwanted side effects. They are contraindicated in patients hypersensitive to them and should be used cautiously in patients with pre existing liver dysfunction . Although they have not demonstrated teratogenic effect, they should be used during pregnancy only when the benefits outweigh the risks.


134

Interactions: Macrolides should not be used with chloramphenicol or the lincosamides. Activity of macrolides is depressed in acidic environments. Macrolide preparations for parenteral administration are incompatible with many other pharmaceutical preparations. Erythromycin and troleandomycin are microsomal enzyme inhibitors that depress the metabolism of some drugs like warfarin, theophylline, carbamazepine and methyl prednisolone. terfinadine, azole antifungals, cisapride

Erythromycin: The antimicrobial spectrum of is narrow, including mostly gram positive organisms and a few gram negative organisms. It the drug of choice in corynebacterial infections , respiratory , neonatal ocular inflammation, or genital chlamydial infections

In small animasl,pigs and poultry: used to treat pyoderma caused by staphylococci, respiratory infection caused by Mycoplasma. The diarrhoea effect is self limiting, except in adult horses it could be fatal. Rectal oedema and partial anal prolapse is seen in pigs. Erythromycin is not recommended in adult horses (oral and systemic) and ruminants (oral). Erythromycin estolate, can produce acute cholestatic hepatitis (fever, jaundice, impaired liver function), probably as a hypersensitivity reaction.

Dose: Dogs and cats: 2-10mg/kg,PO,tid; cattle: 8-15mg/kg,IM,bid; Foals: 25mg/kg,PO or IM, tid; Sheep and swine: 2-6mg/kg, IM,sid; Poultry: 25g/100litres drinking water.

Tilmicosin is used treatment of pneumonia in cattle, sheep and pigs, associated with Pasteurella haemolytica, P. multocida, Actinobacillus pleuropneumoniae, mycoplasma species Tilmicosin phosphate has been effective for treating: .bovine respiratory disease (as effective or more effective than other established treatments: ceftiofur, oxytetracycline, or florfenicol). Injections to horses, goats, swine, or nonhuman primates can be fatal. heart ,the target of toxicity via depletion of cardiac intracellular calcium, resulting negative inotropic efect. As a feed additive , it is effective for controling pneumonia in swine. When injected in swine, tilmicosin has caused toxic reactions and death due to cardiovascular reaction.

Dose: Cattle and sheep: 10mg/kg, SC, every 72 hours; Pigs: 200-400g/tonne feed

Tulathromycin is used in treatment of swine respiratory disease and bovine respiratory disease,characterized by rapid absorption,high distribution and slow elimination. Dose: cattle- 2.5 mg / kg body weight, SC,as a single dose.; Pig: 2.5 mg /kg,IM, single dose

Tylosin is therapeutically used to treat: swine dysentery, pleuropneumonia due to Haemophilus parahemolyticus, colitis in dog, other infections in cats, chickens


134

Mycoplasma canis and Mycoplasma haemocanis infection in dog,cattle Tylosin is alos used for growth promotion in pigs, cattle, and chickens.

Dose: Dogs: 40mg/kg,PO,tid; cats 4mg/kg,IM,sid; Cattle: 10-20mg/kg,IM,bid; Pig: 10mg/kg, IM, bid,25g/100litres drinking water,100g/tonne feed;Poultry: 10 mg/kg, IM, sid-bid 7-10 mg/kg, PO, tid ; 50g/100litres drinking water

Clarithromycin possess broad spectrum bactericidal activity and post antibiotic effect with very good activity against opportunistic infections in Toxoplasmosis, Cryptosporidiosis; H.pylori in peptic ulcer. High concentration in the alveolar macrophages, lung tissue and tonsillar tissue show high penetration of the drug into the respiratory tract cells, a feature that enhances efficacy against typical and atypical pathogens causing pneumonia It is more acid stable, more active against mycobacterium avium complex with lower frequency of GI intolerance. Dose: Dogs and cats: 5-10mg/kg,PO, bid

Azithromycin is slightly less active than erythromycin against staphylococci and streptococci and slightly more active against Haemophilus influenzae.; good activity against many intracellular organism. (Clamydia, Toxoplasma) , mycobacteria ,mycoplasma and Chlamydia; but not against enteric gram-negative bacteria or Pseudomonas. The features: better oral absorption,better tolerance,longer half-life ,higher tissue concentration, broader spectrum of activity than erythromycin and lesser drug interactions . Dose: Dogs : 5-10mg/kg,PO, sid ; cats: 5mg/kg.PO, once daily or every alternate day. Roxithromycin is a longer acting and more stable than erythromycin.Dose: Dogs : 15mg/kg,PO, sid

Tacrolimus is a macrolide ; is an immunosuppressive with similar mechanism of action as another immunosuppressant, cyclosporine to inhibit T lymphocyte proliferation.. It has topical anti inflammatory effects without the atrophogenic effects and metabolic effects of topical GC. It is used topically for the treatment of atopic dermatitis,psoriasis , alopecia areata and effective in canine perianal fistula though at a lower rate than systemic cyclosporine and localized lesions in diseases like discoid lupus erythematosus, pemphigus erythematosus, pemphigus foliaceous.

LINCOSAMIDES: bacteriostatic/ bactericidal depending on the concentration/; particularly active against grampositive,mycoplasma, and anaerobes(most aerobic gram-negative bacteria are resistant). The agents are lincomycin and clindamycin. The antimycoplasmal activity of the lincosamides(clindamycin > potent) is similar to that of erythromycin but less than that of the other macrolides. Lincosamides, macrolides, and


134

chloramphenicol, although not structurally related, seem to act at this same site (50 S subunit of bacterial ribosomes) and thus are antagonistic. Oral and IM absorption being rapid (lincomycin- less well absorbed than clindamycin).They are widely distributed in to respiratory tissue, soft tissue and, bones

In horses,rabbits, chinchillas, guinea pigs, neonates and hamsters: these are contraindicated due to risk of gastrointestinal adverse effects like serious fatal enterocolitis and diarrhoea. Ruminants exposed to oral lincomycin : anorexia, ketosis, and severe diarrhoea.

Interactions: Additive neuromuscular effects with anesthetic agents and skeletal muscle relaxants. Antidiarrheals,adsorbent (kaolin/astringent) significantly decrease absorption oral lincosamides. Antiperistaltic agents, such as opiates, or loperamide /opioid receptor agonist/ may prolong or worsen pseudomembranous colitis by delaying toxin elimination.

Indications: lincomycin HCl: respiratory tract, skin and soft tissue, dental infections, osteomyelitis (cats, dogs) ; swine dysentery, joint infections (pig); necrotic enteritis (chicken); clindamycin: severe anaerobic,respiratory infections . Dose: Lincomycin: 10 mg/kg, IM, bid- Cattle,pig,cats; 20 mg/kg, PO, sid- dog.; Clindamycin: 5-10 mg/kg, PO, bid- Dogs, cats

*****


134

CLINICAL ASPECTS OF CEPHALOSPORIN AND PENEM GROUP OF ANTIBIOTICS

U.SUNILCHANDRA

Cephalosporins, penems (carbapenems), penicillins and monobactams are group of antiobiotics classified under beta lactam antibiotics, sharing common chemical properties and the bactericidal action of bacterial cell wall synthesis inhibition.

CEPHALOSPORINS: Cephalosporins are wide-spectrum β-lactum bactericidal antibiotics exhibiting time-dependent efficacy as opposed to concentration-dependent antibiotics (such as aminoglycoside and fluoroquinolones). Classified in to four generations, based primarily on spectrum of antibacterial activity and resistance to β-lactamases; the spectrum against gram negative organisms and the stability against β-lactamase increase from first to fourth, along with same or reduced spectrum of activity against gram positive organisms, except for 4th generation agents, which have enhanced activity aginst gram positive pathogens.

First generartion: Oral: cephalexin, cefadroxil, cefadrine, cephradine, cephaloglycin; Parenteral: cefazolin, cephapirin, cefalonium, cephalothin, cefacetrile, cefapirin, cefatrizine, cephaloridine

They exhibit igh activity against gram positive bacteria including β-lactamase producing S.aureus.Moderate activity against β-lactamase producing gram negative organisms. Pharamcokinetic featurwes include Rapid absorption, high bioavailibility, unaffected by the presence of food especially in monogastric animals; poor and highly erratic in ruminants, thus being used only in preruminant calves. They show poor penetration across physiological barriers (such as blood brain barrier)

Oral cephalexin, cefadroxil and parenteral cefazolin are the most commonly used ones, primarily for skin and soft tissue infections such as pyoderma caused by streptococci and Staph. aureus, and bacterial endocarditis caused by Streptococcus viridans and S .aureus. Cephalexin used longterm (30days) in the treatment of chronic S.intermedius pyoderma, is associated with increased resistane. Cefazolin is used to treat bone and joint infections in the treatment of open fractures, lymphadenitis, abscesses, pharyngitis etc.

Second generartion: Oral:. Cefamandole, cefotiam, ceforanide, cefonicid, cefmetazole, cefacetrile, cefotiam, cefranide, loracarbef, cefoxitin* cefotetan* (*-cephamycins); Parenteral: cefaclor, cefuroxime axetil, cefprozil, cefuroxime


134

Their use is generally reserved for infections, resistant to first-generation cephalosporins. They are less efficacious than 1st generation against gram-positive pathogens; primarily against S. aureus and S. intermedius; show greater gram-negative spectrum of activity against organisms such as H.influenze, Enterobacter aerogenes and Neisseria species. They are relatively more resistant than first generation agents, to β-lactamases, with poor penetration of the blood-brain barrier. Injections are painful, and may cause thrombophlebitis when administered IV. The broad antibacterial activity may lead to gastrointestinal disturbances and superinfection by resistant microorganisms including yeasts

Cefoxitin and cefotetan (cephamycins): effective against gram negative anaerobes, are used in aspiration pneumonia, bite infections, ruptured intestine gangrene, peritonitis and pleuritis.

Third generartion: Oral:. cefsulodin, ceforanide, cefpodoxime proxetil, cefixime, ceftibuten, cefdinir, cefmenoxime, cefditren pivoxil, cefodizime, cefetamet; Parenteral: ceftiofur, cefotaxime, cefmenoxime, ceftriaxone, ceftizoxime, ceftazidime, cefovecin, cefoperazone, latamoxef* (moxalactam) (* -cephamycin)

They exhibit high antibacterial activity; broader resistance to β-lactamases, though are less effective than 1st and 2nd generation agents against gram positive bacteria. They are most effective against antibiotic-resistant gram-negative aerobes effective against Proteus vulgaris, Enterobacter species, Citrobacter species, Haemophilus species, Neisseria species and Moraxella species. Moderate activity against Gram-positive bacteria and are inferior in activity against Staphylococci. Ceftriaxone, ceftizoxime, cefotaxime and ceftazidime, due to their ability to cross blood-brain barrier are effective in therapy for bacterial meningitis. Cefpodoxime is part of a newer group of orally active cephalosporins. that are absorbed in the form of a prodrug, cefpodoxime proxetil, which is stable in presence of many beta-lactamase enzymes and has been used in skin infections of dogs It also has activity including Moraxella spp,Haemophilus spp, and Klebsiella spp. not active against most obligate anaerobes, Pseudomonas or enterococci.

Ceftazidime and Cefoperazone, are highly active against Pseudomonas aeruginosa among all cephalosporins, compared to ceftriaxone and ceftizoxime, which also have antipseudomonal activity to some extent. Cefoperazone is contraindicated in the herbivore aspecies with an expanded bowel (horses). It has been used by intrmammary route for treating coliform mastitis Cefovecin is generally given as a single injection (SC), the effect lasting for up to14 days . It has about five days of elimination half life; used in dogs and cats to treat skin and soft tissue infections; such as wounds, abscesses and pyoderma and urinary tract


134

infections. It should not be used in dogs,cats less than 8 weeks old, with severe renal dysfunction,breeding animals ,pregnant and lactating dogs

Ceftiofur has broader activity against gram-positive and beta-lactamase–producing strains as well as anaerobes. The injectable crystalline oil suspension formulation of ceftiofur is administered subcutaneously in cattle, in the middle third of the posterior aspect of the ear or in the posterior aspect of the ear where it attaches to the head ( base of the ear), avoiding all the blood vessels. In swine, this is administered to the post auricular region of the neck intramuscularly; the volume of injection at each site being a maximum of 2ml. Ceftiofur is indicated for treatment of bronchopneumonia in cattle, especially when caused by Pasteurella hemolytica or P.aeruginosa. Ceftiofur sodium (50mg/ml powder vials for inj) and ceftiofur hydrochloride (50mg/ml sterile suspension) are the formulations approved for use in dogs, horses, catlle,sheep, goats and swines. Ceftiofur sodium: used intramammary for coliform mastitis as an extralabel use and approved for treatment of urinary tract infections in dogs.

Fourth generartion: Oral:. Cefmetazole, cefditoren; Parenteral: cefepime, cefpirome, cefquinome cefclidine, cefluprenam cefozopranThey have extended spectrum of activity than third, against both gram positive and gram negative organisms ,greater stability against hydrolysis by beta lactamases. Generally, they exhibit excellent penetration ability in to CSF. They are indicated in various infections where resistance to β-lactum antibiotics is expected.Cefquinome, an extended spectrum beta-lactam, is used for treating bovine respiratory disease and mastitis.Pharmacokinetics: The absorption may be enhanced by formulatrion as prodrugs which are metabolized to the active compound in the body. They distribute very well into most of the body tissues and fluids. including bone, pleural fluid, pericardial fluid and synovial fluid with poor penetration of blood-brain barrier, except some third-generation agents: cefotaxime, ceftriaxone ceftizoxime and ceftazidime. They cross placenta with no adverse teratogenic or fetotoxic effects, except a slight decrease in fetal weight( lab. animals). Doses tobe adjusted in severe renal failure/insufficiency to guard against accumulation and toxicity. Cefoperazone, cefamandole and ceftriaxone are eliminated through bile into the feces; and are frequently used in patients with renal insufficiency

Adverse Effects: Gastrointestinal disturbances : Anorexia, vomiting and diarrhoea. Hypersensitivity reaction : manifested as urticarial rashes, fever, eosinophilia, angioedema and lymphadenopathy. ; avoided or used with caution in penicillin allergic individuals. Bleeding disorders: cefotetan, ceftazidime,cefamandole and cefoperazone : increased risk of bleeding due to a decrease in prothrombin activity and anti- vitamin K effects. Critical illness, poor nutritional status, and presence of liver disease are risk


134

factors for hypoprothrombinemia and bleeding; as all cephalosporins can inhibit vitamin K synthesis by suppressing gut flora. Prophylactic vitamin K therapy is recommended when any of these medications is used for prolonged periods in malnourished or seriously ill patients. Hepatic dysfunction: As cefotaxime, cephalothin, and cephapirin are majorly hepatically metabolized before renal elimination, severe liver dysfunction can inhibit their metabolism, indiating the dose to be reduced in these cases . Renal insufficiency :

Nephrotoxicity may occur in patients with renal insufficiency , receiving the full dosage of cephalosporin; and thus dosage should be adjusted .Pain at the injection site: Abscesses or other severe local tissue reactions (IM) and thrombophlebitis(IV) are possible. Other adverse effects noticed in animals include anemia,(dogs: ceftiofur);colic, diarrhoea, laminitis(horses: cefpodoxime proxetil,cefotaxime,cefazolin); local ear swelling (cattle: ceftiofur).

Interactions : Food: Due to the adverse effects like diarrhoea and vomiting associasted with most of the oral administered cephalosporins, , it may be desirable to administer them along with food. Aminoglycosides: most of the other cephalosporins (except cephalothin) demonstrate synergistic activity and are often combined in the treatment of febrile illness in neutropenioc patients. Antacids and H2-receptor antagonists: decrease the absorption of cephalosporins ; thus to be administered at two hours intervals. Nephrotoxic medications: when used with other nephrotoxic medications, such as loop diuretics, especially in patients with pre-existing renal function impairment Platelet aggregation inhibitors: Hypoprothrombinemia and the gastrointestinal ulcerative or hemorrhagic potential of NSAIDS increase risk of hemorrhage if used concurrently with cephalosporins

CARBAPENEMS: Carbepenems are a new class of drugs which are structurally similar to the penicillins. They currently have the widest activity of any antibiotics , being highly active against a wide variety of gram positive and gram negative bacteria . The agents are imipenem, faropenem,maropenem etc.

Imipenem is a broad-spectrum antibiotic with excellent activity against a variety of gram positive and gram negative organism (both aerobic and anaerobic), by comparison to third and fourth generation cepahalosporins.. The high activity of imipenem is attributed to its stability against most of the β-lactamases and it's ability to penetrate porin channels that usually exclude other drugs. The carbapenems are more rapidly bactericidal and less likely to induce release of endotoxin in an animal from gram-negative sepsis. Gastrointestinal disturbances: nausea and vomiting., seizures,hypersalivation and vocalization indicating pain after IM amd SC administration in dogs was noticed.


134

Carbapenems are not absorbed after oral administration except a newer penem faropenem. They are widely distributed to ECF throughout the body and reach therapeutic concentration in most tissues Imipenem is rapidly hydrolyzed by the enzyme, dihydropeptidase, which is found in the brush border of the proximal renal tubule. It is always administered with cilastatin, (an inhibitor of dihydropeptidase) to decrease renal tubular metabolism. The disadvantages of penems include induction of resistance and high cost.

Dose: dogs and cats- 5-10mg/kg, IV or deep IM, q 8 h; horse : 10-20mg/kg, IV, q 6 h

Meropenem is as effective as cefotaxime or ceftriaxione in treatment of bacterial meningitis It has lower incidence of adverse effects to the central nervous system, such as seizures. The recommended empirical dose in dog is 2-5mg/kg, slow IV (with IV fluids) , q 6 h; 5 -10mg/kg, deep IM q8 h or 8-12 mg/kg SC, q 8 -12 h. Individuals who are allergic to the penicillins may demonstrate cross-reactivity with imipenem. Carbapenems are synergistic with aminoglycosides against P.aeruginosa used for intra-abdominal infections, severe lower respiratory tract infections, septicemia and life threatening soft tissue infections

DOSAGES OF CEPHALOSPORINS

1. CATTLE SHEEP AND GOATS

Approved cephalosporin Dose (mg/ kg) Route Interval (Hour)

Ceftiofur sodium Ceftiofur HCL, 50mg/mlCeftiofur crystalline free acid suspensionCefazolinCephapirinCefoperazoneCefuroximeCephacetrileCephalothinCeftriaxoneCefadroxilCephradineCefetamet( calves)

1.1-2.26.615-2010200mg totaldose250mg total dose250mg total dose250 mg total dose 5525-502571020-40

IM ,SCSC IV,IM,SCIMIntramamryIntramamryIntramamryIntramamrySCIM,IVPOPOPOIM

242412

812Single doseSingle doseSD 624121224

2. HORSES

Ceftiofur sodiumCefotaximeCefadroxilCefazolin

2.2-5.520-3010-2010-20

IM,IVIM,IVPOIV

2488-126-8


134

Cephalexin CeftriaxoneCefamandoleCefoperazoneCefoxitinCephalothinCephapirinCefpodoxime CefepimeCefpiromeCeftazidime

25-3325-5010-3030-502010-3020-305-102.21125-50

POIM,IVIV,IMIM.IVIV,IMIM,IVIM,IVPOIMIMIV,IM

612-244-86-8

868-128-12888-12

3. DOGS

Cefazolin Cefaclor Cefixime Cefoxitin Cefotetan Ceftazidime Cefpodoxime CephradineCephalexin CefadroxilCefovecinCephaloglycinCephapirinCefamandoleCeftriaxoneCefoperazoneCefotaximeCeftiofur sodiumCeftizoximeCefuroximeCefetamet

10-3015-305-1015-303025-505-1015-3010-2510-20810-2010-2010-3015-502020-402.225-4010-154-8

IV,IM,SCIV,IM,POIMIV,IM,SCIM,IVPOPOPOPO SCIM,IVIMIMIM,IVIMIV,IMIMIV,IMIVPO

6-86-812-248-126-888-124-8128-1214 Days6-86-88246-88-12248-128-1212-24

4. CATS

Cephalexin CefotaximeCefadroxilCeftriaxone

10-3020-4010-2015-50

IV,IM, SCIV,IM POIM, IV

6-88-121224

5. PIGS

Ceftiofur(Free acid) 3-5 IM 24

6. POULTRY


134

CephalexinCeftiofurCephalothin

25-501.3-2.6

100

POIMIM

8-12248-12

*****


134

RECENT ADVANCES IN ECTOPARASITICIDAL THERAPY

VIJAY KUMAR.M

Ectoparasiticidals are formulated as Sprays, Dips, Pour-ons, Shampoos, Dusts or powders, Foggers, Oral products, Spot-ons, Injectables, Granules, Jetting, Sponge on, Collars etc. A brief introduction to the newer ectoparasiticidals for use in animls is given in this article.

Insect growth regulators and insect development inhibitors: They represent a relatively new category of insect control agents. They constitute a group of chemical compounds that do not kill the target parasite directly, but interfere with growth and development. They act mainly on immature parasite stages and are not usually suitable for the rapid control of established adult parasite populations. Where parasites show a clear seasonal pattern, insect growth regulators can be applied prior to any anticipated challenge as a preventive measure. Examples: Cyromazine, pyriproxyfen, methoprene, fluazuron, fenoxycarb, Lufenuron, Diflubenzuron, Novaluron, flufenoxuron.

Lufenuron interferes with polymerization and deposition of chitin, killing developing larvae either within the egg or after hatching. It is administered PO to dogs (once monthly at a dose of 10mg/kg ) or cats ( 30mg/kg ) or by injection to cats. Female fleas feeding on treated animals are prevented from producing viable eggs or larvae. Suppress the growth of adult fleas up to 32 daysCyromazine, is effective against blowfly larvae on sheep and lambs and also against other Diptera such as houseflies and mosquitos.

Methoprene is a terpenoid compound with very low mammalian toxicity that mimics a juvenile insect hormone and is used as a feed-through larvicide for hornfly ( Haematobia ) control on cattle.

Fenoxycarb usually formulated in collar or spray with either pyrethroid (permethrin) or OPC (chloropyrifos) as an adulticide

NEONICOTINOIDS : The nicotinoids are modeled after natural nicotine. Two compounds in this category are currently available for veterinary use: imidacloprid and nitenpyram . Imidacloprid works by binding to postsynaptic nicotinic acetylcholine receptors in insects. This inhibits cholinergic transmission, resulting in paralysis and death.


134

Imidacloprid is applied as a 10% spot-on topical product and is used primarily to control fleas on both dogs and cats. It also has excellent activity against lice. Nitenpyram is administered PO in pill form to kill fleas in both dogs and cats. It is absorbed rapidly, with maximal blood concentrations reached within 1.2 hr and 0.6 hr in dogs and cats, respectively. While imidacloprid is described as a paralytic, nitenpyram produces hyperexcitability in fleas prior to death PYRAZOLES: This group of compounds has broad-spectrum insecticidal and acaricidal activity. The only member of this group currently available for use is fipronil.

Fipronil : a broad-spectrum pesticide with activity against fleas, ticks, mites, and lice. This is a long-acting poison for dogs and cats.. It kills adult fleas, cockroaches and ants. It is the conventional barrier treatment for termites. Can be toxic to humans Fipronil is absorbed and accumulates in the sebaceous glands, has very low solubility in water, and has prolonged residual activity on both dogs and cats .It is also formulated as baits for cockroaches, ants and termites. It is effective against insects resistant or tolerant to pyrethroid, organophosphate and carbamate insecticides. SPINOSYNS: Spinosad , the only agent must be ingested by the insect, therefore it has little effect on sucking insects and non-target predatory insects. Spinosad works by contact and by ingestion. Contact occurs either by direct application to the insect or by movement of the insect onto a treated surface. Ingestion occurs as insects feed on treated substrate (such as foliage). It is relatively fast acting. The insect dies within 1 to 2 days after ingesting the active ingredient The unique mode of action of spinosad, coupled with a high degree of activity on targeted pests, low toxicity to non-target organisms (including many beneficial arthropods) makes it an excellent new tool for integrated pest management. It should not be used in puppies under age 14 weeks and in pregnant or nursing females. It is available in chewable tablets (presently abroad only), given once a month to kill fleas in dogs only, at a dose rate of 30-60mg/kg .SEMICARBAZONE : Metaflumizone is a new small animal ectoparasitic compound, with a different mechanism of action. It shows no incidence of resistance cross resistance with other insecticides.It is rapidly distributed throughout the surface of the body and do not work through a systemic effect, so there is minimal chance of any drug interactions occuring. . Can be used in puppies from 8 weeks . Presently it is available as a clear, yellow to amber spot-on solution, in combination with amitraz (Each ml contains 150 mg metaflumizone and 150 mg amitraz). It is contraindicated in puppies under 8 weeks of age., sick or debilitated dogs or dogs suffering from heat stress, pregnant and


134

lactating animals. The current available product(Not available in India, presently) is for spot-on application only. Not to be administered orally or via any other route

*****


134

CONSIDERATIONS IN GLUCOCORTICOID THERAPY

U.SUNILCHANDRA

Glucocorticoids (GC) potentially affect every cell in the body and produce a wide spectrum of effects depending on tissue concentration and cell type. GC act indirectly by inducing lipocortin synthesis, which in turn inhibits phospholipase A2, the enzyme responsible for cleaving arachadonic acid from damaged cell membranes. Therefore GC inhibit both the lipoxygenase and cyclooxygenase pathways of inflammation, blocking the formation the leukotrienes aswell as prostaglandins, prostacyclin and thromboxane.

Important Pharmacological effects. 1. Alteration of water and electrolyte balance: manifested by polyuria,polydipsia2. Blood pressure increased, potentiate beta-adrenergic agonists actions3. CNS effects : mood,behavioral changes, diminished response to pyrogens,4. Decrease absorption of calcium and iron from GIT5. Enhance lipolysis and mobilize fatty acids from adipose tissue; stimulates

hyperinsulinemia and results in lipogenesis, decrease in protein synthesis and an increase in degradation,: muscle atrophy, thin skin, and delayed healing can result.

6. Inhibit osteoblasts and stimulate osteoclasts, thereby inhibiting bone healing; reduce the proliferation connective tissue,slowing scar tissue production and wound healing

7. Inhibit virus-induced interferon synthesis; diminish functional capacity of monocytes, macrophages, and eosinophils through inhibition of interleukins

8. ACTH, beta-lipotropin, TSH, FSH, and growth hormone synthesis is suppressed. 9. Hypothalamo pituitary adrenal axis (HPAA) suppression: The suppression of the

inhibition of ACTH by the anterior pituitary gland, suppresses subsequent stimulation of cortisol production depending on GC type, the dose, and duration of therapy.; suppression lasting from one or two weeks to as long as several months . Prevention of hypoadrenal crisis require gradual withdrawal of medication. Animals at risk are generally considered to be those that were on greater than physiological replacement dosing for more than 2 weeks,whose treatment discontinued in the last 6 weeks, and that are under some form of physiologic stress, such as surgery

Classification: 1. Short acting (duration of action < 12 hours) eg: cortisone, hydrocortisone (1 *)


134

2. Intermediate acting(duration of action: 12–36hours) eg: prednisone (4*) prednisolone(4*),methylprednisolone(5*),isoflupredone(50*)and triamcinolone(5 *)

3. Long acting (duration of action > 48hours)eg: dexamethasone (30*), betamethasone (30*),, paramethasone (120*), and flumethasone (120*)

* Antiinflammatory potency as determined by comparison to a cortisol a value of 1.0.Injectable glucocorticoids: To treat shock, doses of GC are 50 to 100 times the physiological level.; phosphate and succinate esters are used IV. .Eg: Μethylprednisolone sodium succinate, Prednisolone sodium succinate,Dexamethasone sodium phosphate To suppress the immune system, doses are about 20 times the physiological level; solutions of free steroid alcohols administered IVor IM; Egs include: Dexamethasone, FlumethasoneTo inhibit inflammation, doses are 10 times the physiological levels.Preparations are acetate and acetonide esters; given IM,SC or intra-articular (into the joint). Absorption of the drug into the systemic bloodstream occurs slowly, over days to weeks. Egs of long-acting formulations include:methylprednisolone acetate, triamcinolone acetonide, isoflupredone acetate, betamethasone dipropionate. Intra-articular GC should not be given if infection is present, or if there is detectable structural damage or instability in the joint.. Surgery should not be performed on GC injected joints for two months following injection Oral corticosteroid formulations are well absorbed. Prednisone and prednisolone tablets are the most commonly prescribed products and are frequently administered for long-term therapy of adrenal gland insufficiency (hypoadrenocorticism) or immunemediated

diseases.Duration of action (DOA) of steroid esters following IM administration is as follows.

1. Soluble short acting: sodium phosphate, sodium succinate;DOA is 30-120 minutes 2. Insoluble intermediate acting: acetate, undecanoate,phenyl propionate, pivalate:

DOA-2-14 days 3. Very insoluble long acting: acetonoide, adamantoate: DOA- several weeks

Topical corticosteroids : the potencywise classification of different topical GC:Mild: e.g. hydrocortisone 0.5-1%, prednisolone, dexamethasone ; Moderate: e.g. betamethasone valerate 0.02-0.05%, triamcinolone acetonide 0.02%, fluocinolone acetonoide.;Potent: e.g. betamethasone dipropionate 0.05%,betamethasone valerate or triamcinolone acetonide 0.1%, diflorasone diacetate ; Very potent: e.g. clobetasol propionate, halobetasol propionate,, betamethasone dipropionate 0.05% in optimised vehicle. Topical corticosteroids are used in ophthalmology to treat chronic superficial


134

keratitis Certain ophthalmic preparations combine antibiotics and a corticosteroid (e.g.Neomycin-polymyxin B,bacitracin with hydrocortisone or dexamethasone) to treat conjunctivitis. GC are also included in topical preparations (most of which contain antibiotics) used to treat minor cuts, scratches, hot spots, or inflammation due to contact dermatitis or allergies, ear infections or inflammations in which GC component helps to decrease the itching.Clinical Indications of GCs

1. Adrenocortical insufficiency (acute,chronic): acute adrenocortical insufficiency (Addison’s disease).Hydrocortisone, methylprednisolone, prednisolone, and prednisone produce minor mineralocorticoid effects in addition to their GC effects and may adequately reverse electrolyte imbalances when administered in conjunction with IV sodium chloride solution; however, methylprednisolone, prednisolone, and prednisone are considered insufficient for long-term control of the potassium-retention or sodium and chloride losing effects of most cases of primary adrenocortical insufficiency and a mineralocorticoid-specific medication is generally indicated. In acute adrenocortical insufficiency, a rapidly acting parenteral corticosteroid with the most mineralocorticoid effect available should be administered in conjunction with vascular volume expansion using isotonic saline. Relative mineralocorticoid effect from the most to the least potency is hydrocortisone > prednisolone/prednisone > methylprednisolone > dexamethasone

2. Allergic disorders: For anaphylactic reactions, corticosteroids play a secondary role to epinephrine and fluid therapy.Dexamethasone injection, methylprednisolone acetate injectable suspension,methylprednisolone tablets prednisolone sodium succinate, triamcinolone acetonide injectable suspension and triamcinolone tablets are indicated in the treatment of allergic conditions such as bee stings, drug allergy, pruritic dermattoses and allergic lung (rhinitis, astma) and GI diseases. In acute case of atopic/flea allergy dermatitis an initial anti-inflammatory dosages alleviate pruritus and self trauma from scratching.. If continued, the lowest dose necessary or, if possible, alternate day therapy with either prednisolone, prednisone, methylprednisolone, or triamcinolone should be instituted. Repeated injections of acetate or acetonide repository injections are not recommended for control of chronic skin disease because of the risk of iatrogenic hyperadrenocorticism. Topical forms are commonly used for allergic conditions like eczema, psoriasis, pemphigus

3. Ocular and Aural Inflammtion(otitis externa) : Topical steroids -for conditions of the anterior chamber; systemic steroids for posterior chamber. Contraindicated in viral


134

infections, fulminant bacterial infections, fungal infections, injuries (ulcers) and glaucoma.

4. Musculoskeletal Inflammation,: several musculoskeletal disorders including osteoarthritis, bursitis, tendonitis, immune mediated rheumatoid arthritis, myositis; should be used in conjunction with therapies that target the underlying cause

5. Adjunct therapy of cardiogenic and hemorrhagic shock: The primary treatment of shock is the administration of large volumes of crystalloid solutions. High doses of GC may aid in reversing some of the effects when administered in conjunction with IV fluids. Dexamethasone sodium phosphate and prednisolone sodium succinate are recommended Short-acting soluble steroids such as the succinate esters are routinely used in the treatment of circulatory shock. When given IV in the early stages of shock, GC and aggressive fluid therapy may improve hemodynamics and survival rates. The use of GC in the treatment of septic shock (endotoxaemia) is controversial and the primary treatment includes antimicrobial therapy and supportive parenteral fluid therapy . High doses of a rapidly-acting GC, preferably of short duration, given in conjunction with fluid and electrolyte therapy within a short period of time, possibly less than 1 hour, after the onset of sepsis.

6. As immunosuppressive in immune mediated haematopoietic and skin diseases: immune-mediated:hemolytic anemia,thrombocytopenia,neutropenia(Dexamethasone, prednisolone, and prednisone) skin diseases like Systemic lupus erythematus, pemphigus complexus and myasthenia gravis of dogs and cats that do not respond well to anticholinesterase treatment, should initially be given GC at anti-inflammatory dose, which may be increased to immunosuppressive levels over a 1-2 week period.

7. GIT diseases: Ulcerative colitis,inflammatory bowel disease, nonsuppurative cholangitis,felinegingivitis, stomatitis- oral therapy with hydrocortisone/prednisolone

8. Respiratory conditions: in acute respiratory distress syndrome in cattle, chronic obstructive pulmonary disease in horses, feline asthma syndrome, aspiration pneumonia, pulmonary oedema from drowning, inhalation injury etc

9. In Organ transplantation: combined with other immunosuppressants(cyclosporine), prednisolone/ methylprednisolone are preferred as they have an intermediate duration of action,easily tapered or converted to alternate day regimens

10. Malignancies/Neoplasia: As a component of most combination regimens for malignancies, in acute lymphocytic leukaemias, CNS tumors, lymphosarcoma, mast


134

cell tumor, multiple myeloma. Anti-inflammatory doses of GC provide the basis for the palliative management of brain and spinal cord neoplasmsThey result in resolution of signs; with a direct effect in reducing the size of some CNS tumors (e.g., lymphoma).

11. Termination of pregnancy/ Induction of abortion: Dexamethasone injection generally administered after the 100th to 150th day of gestation, in conjuction with prostaglandins. Mummification, retained placentas, metritis or dystocia are the possible complications

12. Induction of Parturition : Dexamethasone,betamethasone and flumethasone have been used; generally in conjunction with a prostaglandin.Retained placentas are a common sequale .Parturition may be induced in the last few weeks of gestation involves much less risk to the fetus than earlier termination of pregnancy.Administration of GC more than 1 month before expected gestation often leads to poor neonatal survival.

13. Cerebral oedema/ Hydrocepahlus due to CNS neoplasms/parasites, sarcoidosis, spinal cord injury due to acute trauma : Considerable controversy exists concerning the most appropriate management methods for acute spinal cord injury and cerebral oedema as the functional outcome following spinal cord injury may be influenced by management of systemic blood pressure and by use of methylprednisolone sodium succinate administered within 8 hours of an acute spinalcord injury.

14. Infectious CNS disease: GC may contraindicated in infectious diseases affecting the nervous system, but anti-inflammatory doses of corticosteroids have been recommended for short periods at low doses when neurological signs are severe.

15. Intervertebral disc disease.:Dexamethasone and flumethasone injection; Methylprednisolone, prednisolone, or prednisone, administered at an anti-inflammatory dosage, are indicated as supportive therapy in intervertebral disk disease (Hansen type:1;disk syndrome).However, acute paralysis due to intervertebral disk disease is an emergency usually requiring surgery and/or higher anti-inflammatory dosages of GCs.

16. Ketosis in Cattle: Dexamethasone,flumethasone,isoflupredone acetate and prednisolone acetate injectable suspension are likely to be more effective when administered with IV glucose solutions.For secondary bovine ketosis, other therapies for underlying disease, including local and systemic antibacterials to treat primary bacterial infections is followed..A significant decrease in milk production is expected in lactating cattle.


134

17. Mastitis: Dexamethasone is used as adjunctive therapy in the treatment of selected cases of acute coliform mastitis to relieve some of the systemic signs (due to endotoxin) and mammary gland inflammation. Itshould be administered in conjunction with primary treatments, such as IV fluids, antimicrobials

18. Other less common uses: The use of GC for snakebite may be inappropriate as it may mask signs while not improving outcome. Though sometimes used for stimulation of appetite especially in cats, debilitated animals do not show an increase in appetite and other medications, such as cyproheptadine or a benzodiazepine, are more accepted choices

Side effects : of GC are mainly due to two types: from abrupt withdrawal or after chronic therapeutic use of high doses. The longterm use of supraphysiologic doses to control inflammatory or immunologic disorders. may lead to iatrogenic Cushing’s syndrome, characterized by polyuria, polydipsia, bilaterally symmetric alopecia, increased susceptibility to infection, peripheral myopathy and muscle atrophy, and redistribution of body fat. Longterm suppression of HPAA may cause adrenal gland atrophy and resultant iatrogenic secondary hypoadrenocorticism (acute adrenal insufficiency/ Addisons disease). characterized by lethargy, weakness, vomiting, and diarrhea particularly in dogs and horses. The other adverse effects: flare up of underlying diseses, fluid and electrolyte disturbances (negative nitrogen balance, potassium loss, sodium retention, and fluid retention), inhibition of bone growth, collagen synthesis ,decreased growth rate, delayed wound healing, gastrointestinal irritation/ulceration/perforation. hematopoietic changes;weight gain or weight loss, precipitation of diabetes mellitus, increased susceptibility to infections,immune response suppression,osteoporosis, myopathy, cataracts etc. The side effects of longterm (>2 wk) therapy can be diminished using an alternate-day treatment regimen. Contraindications: GC are contraindicated in : infectious diseases , GIT/ peptic and corneal ulcers, diabtes mellitus, demodicosis, osteoporosis, epilepsy, CHF, renal failure, late pregnancy ,recent major surgery , hypertension, ulcerative colitis and pancreatitis Principles of GC therapy7. GC are usually administered at the lowest dose known to be effective or the smallest

dose that achieves the desired effect in order to limit adverse side effects. 8. Drugs with primarily GC activity and minimal dose to achieve the desired effect is

chosen. Topical or local therapy is preferred whenever possible 9. Once-daily dosing is usually preferred Large steroid doses are administered in

divided doses to reduce local GIT effects.


134

10. Animal should not have been vaccinated several weeks before/ after GC therapy11. In order to mimic the normal diurnal cycle and reduce the risk of adrenal

suppression, GC should be given in morning between 6–10AM 12. Alternate day therapy: every other day treatments are used to maintain remission

without side effects of daily or twice daily administration such as HPAA suppression. 13. Pulse therapy: parenteral administration of supra pharmacological doses of short

acting steroids for shorter periods of time14. Short term therapy: ( <2weeks) : short acting steroids, administered in divided doses

,bid, till the condition is controlled (4-7days) and discontinuing therapy once the condition is controlled

15. Long term therapy: Starting as above for 2 weeks, then bringing the dosage to the lowest possible single dose per day or doubling the dose and give every other day. Giving adjunctive therapy like antihistaminics,to keep steroid dose as low as possible.

16. Tapering the dose and gradually withdrawing before stopping therapy in order to avoid iatrogenic hypoadrenocortisism.

17. The antiinflammtory effect is palliative, routine use in inflammations should be avoided.

18. Short/Intermediate acting GC : more flexible dosing schedules, potent GC effects, lesser suppression of HPAA and less GIT irritation.

Dosages of commonly used GCs: Hydrocortisone: for adrencocortical insufficiency- dogs: 0.5mg/kg.PO.bid; for adjunctive therapy of shock- dogs and cats: 50mg/kg,IVq3-6h; for antiinflammtory activity-dogs and cats: 5mg/kg,PO,bid, IV,IM(sid); for adjunctive in photosensitization-cats: 100-600mg(total) in 1 iL 10% dextrose saline,IV. Cortisone: Dogs and cats: 1mg/kg.PO,IM,sid. Prednisolone: for chronic/subacute adrencocortical insufficiency- dogs: 0.2-0.4mg/kg.PO.sid; for acute adrencocortical insufficiency- dogs: 4-20mg/kg.IVq6h; for adjunctive therapy of shock- dogs and cats: 5-10mg/kg,IVq3-6h; for antiinflammtory activity-dogs and cats: 0.5-2mg/kg,PO,sid,IM; for dermatological /immune mediated disorders- dogs: 1-2mg/kg,PO,bid for 7-10 days,-cats: 2-4mg/kg,PO, q48h 100-600mg(total) in 1 iL 10% dextrose saline,IV. Methyl prednisolone: for anti inflammtory action -dogs and cats: 0.25-1mg/kg,PO; Methyl prednisolone acetate(depot preparation)-dogs: 1mg/kg,SC,IM,cats-2-5mg/kg,SC,IM for CNS trauma, spinal cord injury: dogs: 30mg/kgIV Triamcinolone: for various GC effects: dogs, cats: 0.11-0.22mg/kg,PO,sid; cattle: 0.02-0.04mg/kg,IM; horse-0.1-0.2mg/kg,IM Dexamethasone: for adjunctive therapy of shock- dogs and cats: 4-6mg/kg,IVq3-6h; for antiinflammtory activity-dogs and cats: 0.05-0.125mg/kg,PO,sid,IM; cattle- 0.06-0.1mg/kg,IM.sid; swine-1-10mg(total) IM,IV; for induction of parturition- cattle:


134

20-30mg(total),IM single dose; sheep-8-16mg(total); ; for termination of pregnancy- cattle: 25mg(total),IM,slow IV.; for bovine ketosis: 5-20mg(total)Betamethasone: for antiinflammtory aciony-dogs and cats: 0.025mg/kg,PO,sid, all species-0.04-0.08mg/kg,IM,IV; for induction of parturition- cattle: 20-30mg(total),IM single dose; for bovine ketosis: 0.04-0.08mg/ kg,IM,IV

*****


134

CONSIDERATIONS IN SELECTION OF ANTISEPTICS AND DISINFECTANTS FOR HOSPITAL SITUATIONS

U. SUNILCHANDRA

Antiseptics are used for the surgical sites, surgeon’s hands, traumatic wounds; as antiseptics in soaps, teat dips and dairy sanitizers etc.. The agents are also used to disinfect surgical instruments, apparel, hospital premises. home and farm premises, food processing facilities, water treatment, and in public health sanitation, and, etc. The same compound may act as an antiseptic or as a disinfectant, depending on the drug concentration, conditions of exposure, usage and number of organisms etc.

Three factors are to be considered before selecting a particular agent(antiseptic/disinfectant) for a given application: the type of microorganism the agent has to eliminate(bacteria, virus, fungi or vegetative or spore forms), the environment in which the agent will be used (living tissue/inanimate, presence or absence of dirt/debris) and the characteristics of the agent(corrosiveness, cost and antimicrobial spectrum).

Alcohols: Ethyl alcohol (70% ethanol) and isopropyl alcohol (50% isopropanol) are used. Isopropanol is slightly more potent than ethanol, used as a skin disinfectant and rubefacient. Alcohol-based hand rinses have rapid-acting antiseptic effects,wide germicidal activity,non corrosive, but-fire hazardous risk and limited residual activity due to evaporation ; limited activity in the presence of organic matter and not effective against bacterial or fungal spores

Acids and Alkalies: Strong mineral acids (HCl, H2SO4, etc) in concentrations of 0.1-1 N used as disinfectants; corrosive action limits their usefulness. Acids are used as food preservatives (eg, benzoic acid), antiseptics (eg, boric acid, acetic acid), fungicides (eg, salicyclic acid, benzoic acid),. Acetic acid, 1%, used in surgical dressings and 0.25% acetic acid is a useful antibacterial agent for irrigation of the urinary tract. At 5%, it is bactericidal to many bacteria and has been used to treat otitis externa produced by Pseudomonas, Candida, Malassezia, or Aspergillus spp. Hydroxides of sodium and calcium used as disinfectants, their caustic property usually limits their application on tissues. A 2% solution of soda lye (contains 94% sodium hydroxide in hot water) used is a potent caustic . Calcium oxide, ie, lime (hydrated/ air-slaked lime) soaked in water is used to disinfect premises.


134

Chlorhexidine: has potent activity against gram-positive, some gram-negative bacteria but not against spores; activity is enhanced by alcohols, quaternary ammonium compounds, and alkaline pH, and is depressed by high concentrations of organic matter (pus, blood, etc), hard water, and contact with cork. It is incompatible with anionic compounds, including soap.. A 4% emulsion of chlorhexidine gluconate is used as a skin cleanser, a 0.5% (w/v) solution in 70% isopropanol as a general antiseptic, and a 0.5% solution in 70% isopropanol with emollients as a hand rinse. Chlorhexidine-alcohol mixtures are particularly effective in that they combine the antiseptic rapidity of alcohol with the persistence of chlorhexidine. Because of low potential for systemic or dermal toxicity, chlorhexidine has been incorporated into shampoos, ointments, skin and wound cleansers, teat dips etc

Hydrogen peroxide: (3%). The effervescent action (liberates oxygen when in contact with catalase present on wound surfaces) helps to remove pus and cellular debris from wounds; used for cleaning and deodorizing infected tissue. However, the antimicrobial action is of short duration and is limited to the superficial layer of the applied surface because there is no penetration of the tissue. Benzoyl peroxide can cause skin irritation; has keratolytic and antiseborrheic activity, which makes it useful in treating pyoderma in dogs

Potassium permanganate is an effective algicide (0.01%) and virucide (1%) for disinfection, but concentrations >1:10,000 tend to irritate tissues. Staining of tissues is disadvantage. Chocolate brown coloured old solutions indicate the loss of activity.

Iodine: Elemental iodine is a potent germicide with a wide spectrum of activity and low toxicity to tissues. It is poorly soluble in water but readily dissolves in ethanol, which enhances its antibacterial activity. Used as Tincture iodine (strong/weak). It has wide germicidal activity including fungi and bacterial spores, characteristic odor and is corrosive and has limited activity in the presence off organic matter

Iodophores (eg, povidone-iodine) slowly release iodine as an antimicrobial agent; do not sting, stain; are nontoxic to tissues but may be corrosive to metals. They are effective against bacteria, viruses, and fungi but less so against spores. They retain good antibacterial activity even in the presence of organic matter, and often change color when the activity is lost. Phosphoric acid is often mixed with iodophores to maintain an acidic medium. They are used in teat dips, dairy sanitizers and for various dermal and mucosal infections


134

Chlorine exerts a potent germicidal effect against most bacteria, viruses, protozoa, and fungi (0.1 ppm), but much higher concentrations are required in the presence of organic matter.. It has a strong acid smell, is irritant to the skin and mucous membranes. It is used to disinfect water supplies, inanimate objects (eg, utensils, bottles, pipelines) in dairies. Inorganic chlorides include sodium hypochlorite (Dakin's solution) solutions (bleach) and calcium hypochlorite. Chlorinated lime (bleaching powder): mixture of calcium hypochlorite and calcium chloride; used for disinfection of water, livestock premises, destruction and disposal of carcasses and elimination of pathogens from organic matter.

Phenol (carbolic acid) is bacteriostatic at 0.1-1%;s bactericidal/fungicidal at 1-2%. The bactericidal activity is enhanced by warm temperatures and decreased by alkaline medium, lipids, soaps, and cold temperatures; 5% solution is strongly irritating, corrosive to tissues. Oral ingestion/ excess application to skin can cause systemic toxicity. Cresol: 2% solution of either pure or saponated cresol (Lysol) in hot water is a disinfectant for inanimate objects

Formaldehyde: 1-10% solution of formaldehyde is commonly used as a disinfectant. Glutaral (glutaraldehyde), a 1-2% alkaline solution (pH 7.5-8.5) in 70% isopropanol, is a more potent germicide than 4% formaldehyde. is used to sterilize surgical and endoscopic instruments and plastic and rubber apparatus.

Soaps are dipolar anionic detergents which emulsify lipoidal secretions of the skin and remove, along with most of the accompanying dirt, desquamated epithelium and bacteria, which are then rinsed away with the lather. The antibacterial potency of soaps is often enhanced by inclusion of certain antiseptics, eg, hexachlorophene, phenols, carbanilides, or potassium iodide. They are incompatible with cationic surfactants

Cationic detergents are quaternary ammonium compounds (eg, benzalkonium chloride, benzathonium chloride, cetylpyridinium chloride, cetyl pyridinium bromide/cetrimide) whose activity is reduced by porous or fibrous materials (eg, fabrics, cellulose sponges) that adsorb them and are inactivated by anionic substances (eg, soaps, proteins, fatty acids, phosphates). ; are of limited value in presence of blood and tissue debris. They are effective against most bacteria, some fungi, protozoa but not against viruses and spores. Aqueous solutions of 1:1,000 to 1:5,000 have good antimicrobial activity, especially at slightly alkaline pH. When applied to skin, they may form a film under which microorganisms can survive, which limits their reliability as antiseptics. Concentrations >1% are injurious to mucous membranes


134

Chloroxylenols (Parachlorometaxylenol and dichlorometaxylenol) are broad-spectrum with more activity against gram-positive than gram-negative bacteria.; Active in alkaline pH; however, contact with organic matter diminishes their activity. 5% chloroxylenol solution (in α-terpineol, soap, alcohol, and water) is diluted with water (1:4) for skin sterilization and (1:25 to 1:50) for wound cleansing and irrigation of the uterus and vagina.

Preferred antiseptics i) with antifungal activity: phenols, chlorhexidine, iodine, povidoneiodine, hypochlorite, cetrimide

;ii)withantviralactivity:isopropanol,ethanol,formaldehyde,glutaraldehyde,sodium hyopochlorite,phenol,potassiumpermanganate,hydrogen peroxide, iodophors.

Recommended antiseptics/disinfectants for hospital conditions and instruments: All the instruments have to be immersed for 30 mins and rinsed and autoclaved.

1. 2% sodium hypochlorite: for gloves, syrienges, needles , blood spills on floor, floor washing. lab glasswares

2. 2% benzalkonium chloride: foreceps, thermometer 3. 2% glutaraldehyde: Instruments-catheters, laryngoscope, endotracheal tubes 4. 6% hydrogen peroxide: removal of blood clots from tubes,catheters, dressing wounds 5. Benzalkonium chloride: hand wash, foreceps, catheters , instruments 6. Phenol: disinfecting toilets 7. Povidone iodine: surgical scrub, painting skin, dressing, hand wash 8. Ethyl alcohol: antiseptic at injection site, furniture disinfection

Relative efficacy of classes of antiseptics and disinfectants.

Classs of antiseptics/disinfectants

Type of activity Alcohol Iodine, Iodophors

Chlorine Chlorhexidine

Quaternary ammonium compounds

Glutarldehyde

Bactericidal ++ +++ ++ +++ ++ +++

Lipid enveloped Virucidal

++ ++ +++ +++ + +++

Nonenveloped virucidal

- + +++ + - ++

Sporicidal - + + - - ++

Effec in soap ++ +++ ++ + - ++


134

Effecive in hard water

+* ++ ++ + - ++

Effecive organic material

- - - +++ - ++

*- not to be diluted in water

*****


134


134

CLINICAL PHARMACOLOGY OF MISCELLANEOUS CLASS OF ANTIBACTERIALS

V.C.MEERA

The following is a brief description of various miscellaneous class of antibacterials

Polymyxins : Two members- .Colistin (Polymyxin E)(Available as sulphates for oral and topical use) and Polymyxin B. The spectrum is gram negative bactericidal. They are commonly used topically due to their systemic toxicity(nephrotoxic, neurotoxic, neuromuscular blocking effects) . They are synergestic t with sulfonamide and trimethoprim against variety of enterobacteriaceae.colistin is synergestic with rifampin (In vivo) against multidrug resistant P.aeruginosa and is employed in coliform mastitis.

Vancomycin-: The spectrum is gram positive aerobic cocci and bacilli bactericidal. It is used against staphylococcal bone and soft tissue.infections in in dog.Dogs-3 mg/kg PO, 2 to3 times daily & 10-20 mg/kg IV , 3 to 4 times daily. Ototoxicity and nephrotoxicity, and thrombophlebitis are the adverse effects. Its administration along with aminoglcosides should be avoided as it may potentiate the toxicity of aminoglycosides.

Spectinimycin: is an aminicyclitol antibiotic, bacteristatic against many gram nagative bacteria, mycoplasmas.. It is used in dog cat, horse pigs for the treatment of enteric & respiratory infections.. Dogs & cats- 5-10 mg/kg IM, 2 times daily.; Cattle- 8-12 mg/kg IM, 3 times daily; Calves- 20-30 mg/kg IM, once times daily.; Horses- 20 mg/kg IM, 3 times daily.; Pigs-10 mg/kg PO, 2 times daily.No significant adverse effects have been obseveved (by parenteral route). On high doses may produce neuromuscular blockade. Concurrent use along with tetracyclines or chloramphenicol may produce antagonistic effect.

Rifampicin: is a semisynthetic bactericidal for both intracellular & extracellular organisms. High activity against gram positive bacteia & mycobacteria also against some gram negative organisms like Brucella, shows activity against yeast & fungal microorganisms when combined with amphoterecin B.It is used for treating Rhodococcus equi and other bacterial infections in Foals- 5 mg/kg PO, 2 times daily (in combination with erythromycin 25 mg/kg, PO, 3 times daily.; Dogs & Cats - 5 mg/kg PO, 1- 2 times daily.; For CNS fungal infections; Dogs & Cats-10-20 mg/kg PO, 3 times daily in combination with amphotericin B & flucytocine. Hepatotoxicity in animals with pre-


134

exsiting liver diseases. In horse ( IV ) CNS depression, sweating, heamolysis anorexia. In few cases partial immunosuppression of lymphocytes. GIT disturbances – nausea, vomition, anorexia, abdominal cramps, diarrhea & hypersensitivity reactions are the avderse ffects. As a potent inducer of hepatic microsomal enzymes it may enhances elimination half life of several drugS viz. digitalis, coticosteroides etc.Synegestic effect with amphotericin B against some fungi.

Furazolidone is bacteriostatic , broad spectrum activity ( both gram positive & negative organisms).Also active against giardia toxoplasmas. Coccidia & histomonas. It is used for enteric infectios: Dogs – 2.2 mg/kg PO, 3 times daily for 7 days.; Cats- 4 mg/kg PO, 2 times daily for 7-10 days.; Horses- 4 mg/kg PO, 3times daily; GIT disturbances – inappetence, nausea, vomition, anorexia, abdominal cramps, diarrhea. And CNS effects- tremors, ataxia, convulsions, visual impirement. May be seen

Fusidic acid (Sodium fusidate) : is bacteriostatic effective only on gram-positive bacteria such as Staph. and Corynebacterium. It is used topically for minor local skin infections, wounds. It should not be used with quinolones, with which they are antagonistic

Methanamine (Hexamine) : a urinary antiseptic have antibacterial activity is due to release of formaldehyde in water. It is bacteriostatic agent but becomes cidal in acidic urine. Active against both gram positive & negative organisms.Methamine mandalate - Dogs – 10-20 mg/kg PO, 1-2 times daily.GI disturbances (nausea, vomiting & diarrhea), gastritis, painful & frequent micturation, albinuria, hamaturia, cystitis, CNS symptoms produced occasionally.Use of urinary alkanizing drugs e.g. Na bicarbonate, carbonic anhydrase inhibitors may antagonise its action.Sulphonamides combine chemically with hexamine in urine leads to antagonism.Concurrent use of urinary acidifires such as ascorbic acid, methionine enhances its action.

Tiamulin: Is a semi-synthetic derivative of pleuromutilin. It is typically available for oral use as the tiamulin base or the hydrogen fumarate salt. Tiamuli nHCl as injectable.. It is bacteriostatic against gram positive pathogens including Mycoplasma spp., Spirochaetes (e.g. Treponema) and obligate anaerobes. It is useed for enteric pneumonia complex-Pigs-15 mg/kg IM, once daily for 3 days & 8.8 mg/kg PO, 3-5days

In chickens and turkeys-reductions in water intake. Rarely, redness of the skin, primarily over the ham, may occur in which case it is recommended that medication is discontinued and the affected animals moved to clean pens. In oral overdose tiamulin may cause transient salivation, vomiting and CNS depressions (calming effect), in which case the


http://en.wikipedia.org/wiki/Corynebacterium

http://en.wikipedia.org/wiki/Staphylococcus

http://en.wikipedia.org/wiki/Gram-positive

134

drug should be removed and affected animals should be treated symptomatically and supportively if necessary. Tiamulin should not be administered to animals having access to feeds containing polyether ionophore antibiotics (monensin, lasalocid, narasin, salinomycin, and maduramycin) as adverse reactions may occur. Concomitant use with other drugs that bind to the 50S ribosomal sub-unit (e.g. lincomycin, erythromycin, and tylosin) may lead to decreased efficacy as a result of competition at the active site.

Virginiamycin:is bactericidal against a wide range of organisms including staphylococci, streptococci and enterococci. It is commonly used as feed additive Overdose may result in gastric disturbances, dyspnea, emesis, tremor and ataxia.

Novobiocin: Spectrum mainly gram positive; Most gram negative resistant; but some Haemophilus sp., Neisseria sp., and Proteus sp. may be susceptible.Dogs: 10 mg/kg q8h PO; Cattle:For treatment of mastitis in dry cows:Infuse contents of one syringe into each quarter at the time of drying off; not later than 30 days prior to calving. For treatment of mastitis in lactating cows-using the penicillin/novobiocinproduct. Fever, GI disturbances , rashes and blood dyscrasias after systemic use. It acts similarly to probenecid by blocking the tubular transport of drugs. thus the elimination rates of drugs excreted in this manner (e.g., penicillins, cephalosporins) could be decreased and half-lives prolonged.

Mupirocin: gram positive bactericidal spectrum; is used topically for staphylococcal and streptocococcal skin infections, wounds, burns etc

*****


134

HANDLING OF VETEROLEGAL POISONING CASES

M.VIJAY KUMAR

Generally every veterinarian is encountered with two types of cases in poisoning of farm animals. Accidental and Malicious poisoning. The necropsy of the animals and the rapid diagnosis is helpful in the treatment of other affected animals in case of accidental poisoning. In case of malicious poisoning, which may turn up into medico legal case, the identification of poison is a must to establish the cause of death. In all poisonous cases, chemical analysis of the biological specimens is essential to know the cause of death or illness. Therefore, every veterinarian should know the salient points in collection and despatch of toxicological specimens to a laboratory.

History of the case is of great importance in the diagnosis of poisoning. This includes the number of animals in the farm, number of affected, method of feeding, regularity of feeding, recent changes in the rations or attendants, whether pastures have been sprayed with pesticides or fertilizers, if rodenticides have been used and remnants of the bait removed and disposed properly, storage of poisonous substances etc. Inspection of the surroundings for empty pesticides or paint containers that are not really empty, presence of poisonous plants in the farm environment. Also, the possibility of industrial effluents coming in contact with grazing/watering sources should be given thought of.

POST MORTEM: Necropsy by routine procedure is to be performed as soon as possible after the death of animal. Examine the animal externally and note incisions (for sui poisoning, snake bite etc.,) on the skin or mucous membranes. Examine the oral cavity for corrosive lesions (acids/alkali) or changes in colour of mucous membrane (nitrate, co, cyanide poisoning). As most of the toxins gain entry through gut, examination of gut mucosa, the contents, their smell, colour and pH (acids, alkali, urea) is a valuable guide in diagnosing toxicoses. Poisoning by salts of heavy metals results in significant post mortem lesions but poisoning by alkaloids like strychnine produces very feeble lesions.

The natural orifices, sub-cutaneous fat tissue, muscles, bones and teeth (in fluorine poisoning), body cavities, and internal organs should be examined. The stomach should be punctured rather than cut open for organoleptic examination to note the character of smell. Puncture ensures greater accuracy and a longer time smell. Some of the poisons which emit characteristic smell are: bitter almond -hydrogen cyanide poisoning, garlic


134

odour - phosphorus poisoning, rotten garlic or horse radish smell - selenium, tobacco odour –nicotine, acetylene odour - zinc phosphide and ammoniacal odour- urea.

Check the pH of the stomach contents by pH paper. Any variation in the normal pH of the sps. being examined indicates abnormality. (In urea poisoning-alkaline pH is observed in rumen liquor due to release of ammonia).

The colour of stomach contents also indicates the cause of poisoning. Copper salts impart a greenish blue colour whereas picric and nitric acid impart yellow colour to the contents. The contents of the stomach vary from traces to flakes of paints or lead objects, grains or baits, seeds etc., like wise small and large intestine should be examined. Blood should be examined for its colour and clotting characters. Cyanide poisoning imparts cherry red colour, arsenic imparts rose red colour and nitrate poisoning turns blood brown in colour. In abrus and cyanide poisoning-blood remains fluid after death.Examination of other visceral organs should be done in relation to their size, colour etc. eg: - spleen size is decreased and colour is changed to dark brown or black in copper poisoning and spleen size is increased in T-2 mycotoxicoses.Lymph nodes are swollen, haemorrhagic, oedematous and dark upon exposure to radiation. Bone marrow becomes pale and gelatinous with yellowish tint.The description of morphological changes should be noted clearly and absence of changes should be notified. The most important lesions found should be underlined.

In case of small animals (poultry, small dogs, lab animals) the cadavers are sent as it is, in case of large animals the stomach contents are collected from the vicinity of patho anatomic changes in the gastric mucosa. If there are no changes a representative sample is collected, but in medium sized animals the stomach tied at oesophageal and duodenal end, intestine tied at both ends and bladder with tied ends is sent separately.

Collection of samples: A successful toxicological investigation requires appropriate specimens, history and clinical signs, necropsy lesions and circumstantial evidences. All the specimens are to be taken in separate containers (polythene jars/covers), securely tied, properly labelled with particulars of date, case No., organs collected, species, name of preservative used etc. A sample of the preservative used, brief history of the case along with treatment given particulars should be sent. It is always preferable to send the specimens through a special messenger. In medico legal cases, the specimens should be sealed in the presence of a witness. The quantity for the kind of sample to be sent is as follows.


134

Wholeblood:10-20ml;Serum:10-20ml;Milk:50-100ml;Urine:50-100 ml;Water: 200 ml; Faeces : 50 g ; Feed : 0.5 - 1kg.

Mode of preservation : 1. Ice for about 72 hrs. 2. Alcohol (95% ethyl alcohol) 1 ml/g of tissue is the ideal preservative for toxicological specimens. Formaline should never be used as it hardens the tissue without giving scope for scraping and interferes in the analysis. Blood and serum should be refrigerated and never frozen. A sample of the preservative used should be sent. It is always better to have a duplicate sample stored properly in a refrigerator for future reference Sample for analysis should include a suspected source material; often gut contents, so that ingestion of suspected material can be proved. Secondly, a sample of tissue (depending on tissue affinity of the suspected poison) must be included, to prove that absorption of the poison has occurred. It is always advisable to include a sample of liver to confirm absorption of orally ingested poison. In survival cases the following materials may be sent for analysis:Stomach wash, ruminal contents, vomitus, blood, urine, saliva, dung, water and feed, suspected forage/ poisonous plant/s is the ideal samples for laboratory analysis. Most xenobiotics are ingested. Therefore, one of the unique advantages of analyzing gastrointestinal contents is that qualitative tests can be easily carried out in order to determine the animal has oral access or not. Guidelines for submitting specimen for toxicological examination is listed in Table 1.

Table 1: Toxicological specimens for laboratory examination

Sl.No. Suspected poison

Specimen required Remarks

1. HCN/Cyanide Forage / ingesta, whole blood

Liver

Rush samples frozen in air tight bottle to laboratory

GIT/ Stomach contents in 1% mercuric chloride is ideal

2. Organochlorine pesticides/

Chlorinated hydrocarbons

Cerebrum, fat, liver, kidney, ingesta

Use only glass containers,

Avoid aluminum foil for wrapping specimens

3. Organophosphates &Carbamates

Feed, ingesta, liver, urine -

4. Znic phosphide Liver, kidney, gastric contents

-

5. Nitrate/nitrite Forage, ingesta, body Ingesta in chloroform or


134

fluids, Serum . Ocular fluid water samples

formalin filled air tight container

6. Oxalates Fresh forage, kidneys Fix in formalin

7. Ammonia/Urea Whole blood or serum, urine Rumen contents

Frozen / 1-2 drops of saturated solution of mercuric chloride

8. Heavy metals(Lead, Mercury)

Kidney, whole blood, liver and urine

Heparinized, do not use EDTA

9. Mycotoxins Forages, feed sample, liver, kidney, brain

Use airtight containers or plastic bags. Cloth bags for dry feeds

Note: Always send a sample of preservative if used in separate container with proper

label *****


134

GENERAL LINE OF TREATMENT OF POISONINGSM.VIJAY KUMAR

In majority of cases of poisonings, treatment with an antidote is not possible, instead prompt medical intervention to improve the condition of the animal can ensure its survival. These practices focus on promoting the removal of the poison or neutralizing it, whilst maintaining the vital functions of the animal.

Decontamination of the skin: Some substance (hydrocarbons, acids, alkalis, agrochemicals, etc.) may, as a result of an accident or a spillage, contaminate the feathers or fur of animals. In general it is important that in such circumstances the following are undertaken:

Epidermal structures (wings, nails, claws, feathers, fur) should be cleaned with the greatest care, paying particular attention to areas such as the ears, between toes, etc.

Avoid licking and ingestion of the poison, and to limit cutaneous absorption.Use soapy water (preferably a soap with a low pH), rinsing repeatedly with copious tap water

Dry carefully and thoroughly (e.g. with a hair dryer)The following must never be used: organic solvents (alcohol, white spirit, etc.) or oily substances which may actually increase percutaneous absorption of the toxin.

Do not rub the area vigorously; cleaning and drying must be gentle but thorough Gastric emptying: Emetics:Use emetics if ingestion has taken place within the preceding 2-3 hours. Never induce vomiting in following circumstances: If caustics or hydrocarbons have been ingested; If the condition of the animal does not allow such treatment, specifically if the patient is presenting with convulsions (unless controlled), coma or severe respiratory difficulties; this avoids any secondary complications due to aspiration.; in pregnancy and ingestion of slow releasing drug formulations. Apomorphine: a central depressive effect and the possibility of cardio-toxicity (arrhythmias) -Dogs: 0.05-0.1 mg/kg s.c or im; contraindicated in cats or pigs; Xylazine: acts within 10-20 minutes; 0.25-0.5 ml of a 2% sol.,s.c.Ipecachuana (10% syrup) for dogs and cats: Acts in 20-30 minutes; orally, 10-20 ml for a dog, 2-5 ml for a cat administered in a phased manner. Alternatives: Sodium chloride (salt), p.o, 1-3 teaspoons in warm water; Hydrogen peroxide, by mouth, 1 ml/kg; Copper sulphate is not recommended as it is an irritant and facilitates the absorption of poisons. Preferred in pigs (4% solution, max: 60ml,p.o)Gastric lavage in dogs is indicated: if ingestion has taken place in the preceding 2-4 hours and on anaesthetized animals with endotracheal intubation. Use 10 ml/kg of an


134

isotonic solution of sodium chloride (occasionally sodium bicarbonate); repeat the procedure until the washout fluids is clear. Emergency gastrotomy with manual emptying may be necessary in some cases of plant poisoning or indigestible materials (such as plastic, polyurethane foam).

Purgatives: Never use irritant purgatives and oil-based purgatives as they facilitate absorption. Sodium sulphate, magnesium sulphate are preferred; PO, as enema, using solutions of various strengths (make up to 20%):Small animals : 2-25 g, Large animals: 100-200 g (max: 300 – 400g); Liquid paraffin (mineral oil), by mouth:Dogs: 5-15ml, Cats: 2-6ml

Diuretics: Increase glomerular filtration by instituting a forced diuresis or osmotic diuresis: 5% glucose solution, by slow IV infusion: Large animals: 2-5 ml/kg per 24h, Small animals: 5-20 ml/kg per 24hr; 10% glucose solution, by slow IV infusion:

Large animals: 0.5-1 ml/kg per 24 h, Small animals: 1-2 ml/kg per 24 hr; 10% mannitol solution, by IV infusion:Large animals: 1-2 ml/kg per 24 h, Small animals: 2 ml/kg per 24 hr; :Frusemide (im or iv), Large animals: 0.5-1 mg/kg, Small animals: 2.5-5 mg/kgReduce tubular reabsorption by modifying urinary pH.: Forced acid diuresis to eliminate weak bases can be done by:Ammonium chloride, PO: Large animals: 20-40 g, Small animals: 2-5 g; Arginine chloride, im, or iv-Large animals: 7-10 g, Small animals: 0.1-0.2 g/kg; Ascorbic acid, iv, all species: 40 mg/kg

Forced alkaline diuresis to eliminate weak acids: Sodium bicarbonate, 1.4%w/v, iv infusion, Large animals: 2-4 ml/kg per 24 hr; Small animals: by regular monitoring of the acid – base balance (number of ml to perfuse = base deficit (in mmol) x 0.6 x body wt in (kg)ringer’s lactate, IV: all species: 5-10 ml/kg per hr; Use a diuretic such as acetazolamide

Dialysis: In cats and dogs peritoneal dialysis with an appropriate dialysate 20-25 ml/kg is suggested. Repeat the procedure several Times as necessary. Very effective in case of renal failure/renotoxicity. Commercial preparations meant for human use can be employed

Neutralization of poisons with in the gastrointestinal tract

Adsorbents Activated vegetable charcoal (fine medicinal charcoal).-the most effective and most highly polyvalent adsorbents. They can be administered preferably as a suspension in water, several minutes to 24 hours after ingestion, if possible before any emetic. Large animals: 250-500 g, Small animals: 5-50 g; Other adsorbents: Magnesium


134

oxide (magnesia), Kaolin, Universal antidote (vegetable charcoal 10g+ magnesia 5g + kaolin 5g + tannin 5g with water added up to 200 ml)

General chemical antidotes: Substances which form a complex or insoluble precipitate with poisons and neutralize them in the gastrointestinal tract. The effects are often limited and debatable. This category includes: Water-containing albumens (proteins which are capable of forming insoluble complexes with heavy metals and which neutralize acids and bases); Tannins (these precipitate heavy metals aluminum, lead, silver and some alkaloids) ; Less useful against copper, mercury and nicotine), Lugol’s iodine can partially precipitate heavy metals like Pb, Hg, Ag and Strychnine. and Ferric hydrate .

Milk is commonly believed to act as the best general antidote; in fact, milk promotes the absorption of liposoluble poisons. A cardinal rule, therefore, is “never administer milk”.

Additional treatment measures: vary according to the symptoms observed, important agents used to support vital functions (respiration and circulation) are: Doxapram: A respiratory stimulant, Dog/Cat: 2 mg/kg, iv, repeat as required ; Caffeine and theophylline: Cardiovascular and respiratory stimulants, with diuretic action. Dosage: 100-250 mg iv, im, hypodermally or as required and Nikethamide:. Dog: 22-44 mg/kg, im, iv.

Rational Use of Charcoal : Charcoal is ineffective against cyanide. It can adsorb vitamins/minerals and continued use may prove to be harmful. Make slurry of the activated charcoal using lukewarm water. 2-8 g/kg should be given in a concentration of 1g/5-10ml water by a stomach tube using either a funnel or a large syringe. Administer a cathartic (sodium sulphate or magnesium sulphate) 30 minutes after the administration of charcoal. In pet animals this technique can be modified if the charcoal is used in conjunction with an emetic or gastric lavage (Normal saline: 10 ml/kg) with endotracheal intubation.

*****


134

CLINICAL MANAGEMENT OF POISONINGS OF VETERINARY IMPORTANCE

B.KALA KUMAR

In veterinary field toxicities are often found as a result of ingestion of poisonous substances while grazing or through water. Suspicion of poisoning is also aroused when illness occurs in a number of previously healthy animals, all affected at a same time, sharing the same signs, necropsy findings, to the same degree of severity. Poisoning in most occasions is accidental in farm animals, but may occasionally be deliberate .

SOURCE OF POISONINGS

1. Insecticides:Insecticides are the major source of poisonings in livestock.. Most of the insecticides are basically ‘neurotoxic’, hence they may share some of the clinical signs, Insecticides can be classified in to following categories: 1. Organochlorines: Eg: Aldrin, Endosulfan, Lindane, Dicofol etc 2. Oraganophosphates. Eg: Acephate, Malathion, Parathion, Methyl parathion, Dimethoate, Phosphamidon,, Chlorpyriphos, Chlorfenvinphos, Monocrotophos etc 3. Carbamates. Eg: Carbaryl, Metacil, Dimetan, Pyramat etc. 4. Pyrethroids (Synthetic): Deltamethrin, Cypermethrin,Permethrin, Allerthrin etc. 5. Miscellaneous: Chloro-nicotinic acid (nicotine), Arsenic compounds,Captan

Organochlorines: By virtue of their high lipid solubility these agents can enter the neuronal membrane with ease and therefore interfere with normal functioning of the nerve membrane sodium channel. The clinical signs of toxicity can be broadly categorized in to:

Behavioural signs - Anxiety, aggressiveness, abnormal posturing, maniac symptoms like jumping over inanimate objects, wall climbing etc. Neurological signs – Hypersensitive to external stimuli, spasm and twitching of fre-and hind quarter muscles, fascicualtions of facial and eye lid muscles and variations in body temperature (subnormal temperature to hyperthermia, up to 116F). Autonomic effects: Marked salivation (normally thick/ sticky saliva), Mydriasis, frequent urination, defecation and lacrimation.

Organophosphates: Clinical essentially appears as a result of irreversible inhibition of AChE, causing accumulation of acetylcholine in the neuro-muscular junction leading to ‘spastic paralyses. The cause of death is due to respiratory collapse. Muscaranic signs (miosis, watery, drooling saliva, urination, colic and /or defecation, lacrimation are the


134

common signs followed by nicotinic effects (muscle fasciculations, tremors) and C.N.S effects( ataxia, convulsions and later depression of respiratory and circulatory centers). Hypotension, bradycardia and dyspnoea are observed in poisoned animals.

Carbamates: The inhibition of AChE enzyme by carbamates is ‘reversible’, therefore, on most occasions animals recovers on own unless ingested large quantity of pesticide.

Synthetic pyrethroids: Although these compound process low insect: mammalian toxicity ratio, treatment of poisoned animals may be a difficult task probably because of multiple mechanisms involved in toxicity and variations among pyrethroid class (type-I & type-II). Hypersalivation, lacrimation, mucoid nasal discharge, excitement, in-coordination, extension of limbs are observed in deltamethrin toxicity in buffalo calves. Few pyrethroids also cause contact dermatitis.

2. Rodenticides:.

Anticoagulant rodenticides: These include warfarin (less used now a days) and second generation anticoagulant rodenticides viz: Bromadiolone , brodifucoum. The main source of poisoning is the ingestion of residues of the rodenticides or baits intended for killing rodents.. The poor coagulation mechanism cause massive internal haemorrhages over aperiod of time. Normally after period of about 2-5 days clinical signs appears and these include anorexia, pulmonary coughing (epitaxis, dyspnoea),hypothermia, haematuria, stiffness of hind quarters and sudden death. Internal haemorrhage, blood in the GIT(gastroenteritis), haemopericardium and menigeal/cerebral bleeding and haemorrhages in joints are the pathological lesions one can observe during necropsy. The affected animals should be shifted to quiet and warm place and the line of treatment include Vitamin-K1 in physiological saline (Vitamin-K3 not recommended) and cardio-vascular support.

Zinc phosphide/ Aluminium phosphide: It is one of the cheapest and quite effective rodenticide. Monogastric species are more sensitive rather than ruminants. Clinical signs include anorexia, lethargy, abdominal pain, bloat (in ruminants), deep respiration, ataxia, prostration and dyspnoea, gasping, convulsions and death. Post-mortum lesions include pulmonary congestion, edema, sub-pleural haemorrhages, congestion of liver and kidneys. Acetylene odour may be detected in stomach. No specific treatment is possible, however symptomatic and supportive care maybe given. Gastric lavage with 5% Sodium bicarbonate, Calcium boro-gluconate injection, anticonvulsants and measures to prevent shock can be undertaken as a life saving measure.


134

3. Herbicides & Fungicides:Dinitro-compounds: Dinitrophenol, DNP; dinitro-orthro cresol, DNOC); are some of the commonly used as herbicides. Accidental ingestion of foliage sprayed with these compounds may lead to toxicity in ruminants. These compounds induce methaemoglobinemia (intravascular haemolysis),hyperthermia, dark coloured blood and gastroenteritis. Rapid onset of rigor mortis, yellowish-green coloured tissues/urine may be recorded during post mortem examination.

Zeneb & Thiram: Zeneb (Zinc-ethylene dithiocarbonate) and Thiram (Tetra-methyl thiuron sulfide) are the two most commonly used fungicides in agricultural practice. Although acute poisonings is less likely to observe in field, chronic toxicities may get unnoticed. Zeneb can induce thyroid hyperplasia, hypothyroidism, degenerative changes in myocardial, skeletal tissues and depletion of testicular germ cells. Thiram exposure may cause conjunctivitis, rhinitis, bronchitis, abortion (ewes) and teratogenic effects.

4. Hydrocyanic acid (HCN) /Cyanide:The most prevalent form of HCN poisoning in livestock is caused by various cyanogeneetc plants capable of producing hydrocyanic acid. Such plants contain cyanogenetic glucocides (dhurrin in sorghum, amygdalin in bitter almond etc.) which hydrolyzed in to HCN in ruminants. Wilted, drought affected, injured (chopping, rinsing etc.) plants are more dangerous than fresh plants because of their preformed HCN. Any plants possessing 20mg HCN per 100gm (wet wt.) may serve as potential source of HCN poisoning. Other source of cyanide poisonings are: industrial grade Na/K and calcium cyanide (also fertilizer) and effluents from vicinity of electroplating/metal coating industries workshop.

Hyperoxygention of blood would lead to cherry red/ bright red colour of venous blood . Intoxicated animals shows salivation (frothy), bradypnoea, mydriasis, ataxia,tremors, epileptiform scizure, cardiac arrhythmia and clonic-tonic convulsions. Invariably loss of conscious, coma and death with several jerky and convulsive movements if poisoned animals are not attended with in a with in 1 hour after the appearance of clinical initial signs. Odour of the breath is ammonical/ bitter almond due to benzaldehyde production (often bloating, regurgitation is observed). Opening of rumen during post-mortem examination impart similar odour. Animals suspected for HCN poisoning must be differentiated from nitrite and other sr milar agents before initiating antidote therapy . In addition to antidotes, per oral administration of Cobalt chloride(10 mg/kg)and glucose is also indicated.

5. Nitrate/Nitrite:Drought is one of the root causes of nitrite toxicity in cattle/buffaloes. Nitrates are reduced to nitrite in ruminates. Otherwise, pigs are most sensitive species for nitrate toxicity. Contamination of drinking water with sewage, several plants species


134

(Amarantus sps,Palak etc.), plants grown in highly acidic soil, water logging and rich nitrated fields / effluents zone, deep well water or pond water originated from leaching of top soil (after -nitrate fertilizer application) are some of the common source of nitrite poisonings. Water soaked/entry of moisture may also render paddy hays/ corn in to nitrite rich within 18-22 hours. Frequent application of fields with non-toxic weed killer 2,4-D and nitratic fertilizer favour accumulation of nitrtes in plants. Any forage that contains over 1.5% nitrate (expressed as pot. nitrite) is considered relatively unsafe for livestock and should be fed with extreme caution. Nitrite ions induce meth-haemoglobenaemia as well as marked vasodilatation. Clinical signs include cyanosis, staggering gait, muscular tremors, rapid pulse, dyspnoea and dilated pupil. Opisthotonus, polyurea, chocolate brown colour of the blood and cyanotic mucous membranes are the characteristic features of nitrite toxicity. Untreated animals die with out a struggle. Reducing agents like Methylene blue or Ascorbic acid are the antidotes (see table 2 for details). Mineral oil or mucilaginous substances and diluted vinegar (4-5 lt. in cold water, per os) must be administered to counter GI irritation and further reduction of nitrates in the rumen respectively. Cardiovascular support (vasoconstrictor); and stimulants to counter prostration.

6. Poisonous plants: Toxicities/ death due to ingestion of poisonous plants are also often being the etiology of poisoning in the farm animals. Commonly with plant poisonings there are perplexing epidemiological features. For example, animal already grazing in the dangerous field are often unaffected while recently introduced may be poisoned. Drought, starved, ailing from pica, hungry, ravenous animals, curiously excited animals (often do not eat), and young animals less discriminate plants with different texture (attraction). Poisonous plants often show geographical limitations in their distribution, particularly industrial enterprises may create ‘poison hazard’ in local areas (Ipomea carnea, Amaranthus spinosus) and certain agricultural practices / soil type may also pose toxicities (eg. Nitrite, Selenium). Severe drought followed by rain/moisture/humid atmosphere favour accumulation nitrite in many plants. Similarly re-emergence of fresh leaves following harvesting also contains dangerous levels of HCN.

Essentially the source of plant poisoning can be classified into: a. naturally occurring b. Commercial crops/byproducts and c. Conventional and non-conventional fodders. Immature sorghum, maize, flax (linseed); Manihot esculenta (tapioca) newly emerging bamboo shoots and rubber leaves are the common source of HCN poisonings. Accidental ingestion of castor bean, rotten beat roots, adult nicotine leaves,Mimosa invisa (used to increase nitrogen fixation in soil) may become fatal.. Plants or foliage belonging to Brassicaceae sps.(Cruciferae) family i.e kale, rape,turnip, cabbage,reddish plants and


134

mustard seeds or meal may elicit severe toxicities in animals when fed /ingested large quantity due to the presence of glucosinolates in such plants..Digestive disturbance(enteritis),goiter polioencephalomalacia (rape blindness), pulmonary emphysema are the sequelae. Bloat, photosensitization is also observed. Affected animals are to be treated symptomatically.

Feeding of urea treated straws in excess/or fed to un-acclimatized animals may lead to urea poisoning, long term feeding of subabul may lead to hypothyrodism and feeding of fungus infested straws (sorghum, paddy or leguminous fodders) may pose threat of mycotoxicosis when fed relatively for a long period. Ficus tsjhela (Karnataka-Kerala boarder, Western Ghats); Acccia leucopholea (HCN), Amaranthus spinosus (nitrite); Jatropa curcus (purging nut); Crotalaria juncia (hepatotoxic pyrrolizidine alkaloids: monocrotaline);Flax(linseed, HCN); Ipomea carnea (LSD alkaloid like effects, also source of nitrite and cause photosensitization). Strychnous nux-vomica (coastal Karnataka); Abrus precatorius (Gulaganji); marking nut, Calitropis gigantica (yakka), croton oil and Yellow oleander are also some of the plant source of accidental poisonings and/or recorded in case of malicious poisoning in animals.

Antidotes and supportive treatments for common poisonings in large animals

Poison/toxicity Antidote/ treatment Dosage and method of treatment

Hydrocyanic acid (HCN) /Cyanide

Sodium nitrite followed by Sodium thiosulfate

Administer 1% sodium nitrite @ 15-25mg/kg,i.v followed by 25% sodium thiosulphate @ 1.25gm , slow i.v Na nitrite + Na thiosulfateCattle: 3gm + 15gm in 20ml water, s.c; Sheep/goats: 2gm+5gm in 15ml water,s.c. Cobalt chloride @10.2 mg/kg, per os; Approx. 4 lt. vinegar in 10-20lt. cold water; A large dose of vitamin B12 and anticonvulsants, if necessary. Give cobalt chloride 10mg/kg per-orally. Fluid therapy with dextrose-saline is ideal

Nitrate/nitrite Methylene blue

Or

Ascorbic acid

1% Methylene blue @ 8.8mg/kg, i.v and repeat 30 min later and if necessary administer at 6-8hr. interval Broad spectrum antibiotics intra-ruminally; Administer 8-10L cold


134

water and give osmotic purgatives Treat for hypotension/shock, (vasoconstrictors like 1:1000, 0.5 ml adrenaline, slow iv); Blood transfusion, if possible

Heavy metals

(Arsenic,antimony, mercury)

Arsenic/Mercurial insecticides)

Arsenic poisoning

British anti-Lewisite(BAL)

d-penicillamine

BAL: 3mg/kg as 5% mixture of 10% benzyl benzoate in mineral oil. Give deep i.m injection every 4hr. on first two days, every 6hr. on third day and then b.i.d for next 10 days. In cattle and horse sodium thiosulfate can also be used @ 8-10gram in the form of 10-20%solution (i.v) or 20-30gram per-orally in 300ml water.

Fluid therapy and other supportive treatment as required. Administer @ 30-40mg ,i..v + 60-80mg/kg; P.O, b.i.d or t.i.d for 3-4 days

Urea No antidote

Reduce the rumen pH

Administer 20-30lt. water and drench 4-6lt. 5 % acetic acid ; Anticonvulsants, if required

Strychnine

(Strychnous- nux vomica)

Phenobarbital sodium

Chloral hydrate

Phenobarbitone sodium,30mg/kg,i.v

Chloral hydrate @ 5g/45 kg, i.v

Drench tannic acid and then purgative

Rest the animal in cool, noise free & in dark room after a dose of purgative

Lead Calcium disodium EDTA Make 6.6% solution and administer @ 73 mg/kg,i.v (repeat or two treatment daily for 3 days if required). Combined thrapy with thiamine HCl @2-4mg/kg/day, s.c is more effective, Anticonvulsants, if required

Warfarine Vitamin- K1 Vitamin-K1: 300-500mg, S.C,every 4-6hr.Blood transfusion transfusion @ 20ml/kg or plasma @ 9ml/kg body wt;


134

Bromodiolone Sedatives/tranquilizer

Pyrethroids

(Deltamethrin,

Cypermethrin etc.)

No specific antidote, but

Diazepam HCl + Atropine SO4

Diazepam: 0.5-2 mg/kg, i.vAtropine SO4 as required

Activated charcoal (1-2kg), P.O Fluid therapy

Carbamate insecticides Atropine sulphate 0.25mg-0.5mg/kg,give ¼ intravenously and remaining ¾ by intra-muscular or sub-cutaneous route

Organophosphates Atropine sulphate +

2-PAM

Or

DAM(diacetyl -monoxime)

Atropinization: 0.25mg-0.5mg/kg,give ¼ i.v,remaining ¾ by i.m or s.c for every 3-6 hours. Observe for papillary dilatation and recovery symptoms and continue treatment as required.

2-PAM: 20%solution @ 25-50mg/kg,i.v or intra-muscualrly, Activated charcoal,P.O

Fluid therapy and supportive care

Organochorines ( D.D.T;, B.H.C & endosulphan etc.,)

Pentobarbitone sodium Or Chloral hydrate

30mg/kg,i.v and supportive care

5g/45 kg ,i.v and supportive care

Dinitro-herbicides (Dinitro-orthocresol-DNOC & Dinitrophenol-DNP)

In ruminants only: Treat for Methaemoglobinemia with methylene blue

Or

Ascorbic acid

Methylene blue: 2-4%,8-10mg/kg,i.v every 8hr. Or Ascorbic acid: 5-10mg/kg,i.v; every8hr. for first 24-48hr.Note: Do not give antipyretics to control hyperthermia. Administer saline purgatives. Fluid therapy with DNS

*****


134


134

CARE AND MANAGEMENT OF CRITICAL PATIENTS IN CLINICS

VIVEK.R.KASARALIKAR

Critically ill patient is special challenge to the clinician because the underline problem is not evident for about 24 to 48 hours after initial presentation. Expeditious therapy in right time can be life saving, whereas delayed adequate therapy may be ineffective therapeutic failure. Most common clinical conditions in ambulatory patients are trauma with internal/ external hemorrhage, poisoning and post surgical complication. In fact, specialized care of emergent patient begins with initial phone call from the owner and instructions to be given regarding first aid and transport procedures. Level of consciousness, breathing pattern and external hemorrhage should be enquired on priority.

The important first aid measures are:

Immobility and transport on firm flat surface Mouth to nose resuscitation in critical patient which is unconscious and not breathing

(Ten to twelve times per minute) Pulsating arterial bleeding is controlled by digital pressure and pressure bandage Penetrating foreign objects should be left in place till specialized help is available Head elevated by 200 in altered mental status after head or spinal injury

Evaluation and initial treatment: Three important assessment criterion in emergency patients are A, B and C by evaluating certain parameters .

A – Airway: Airway patency should be evaluated on priority. Noisy breathing without need of stethoscope suggests Large airway problem e.g. trachea and bronchus, whereas, inspiratory dyspnoea implies extra-thoracic airway compromise. Loud expiratory sounds reflect towards pathology of intra-thoracic airway including bronchioles and lung parenchyma.

B – Breathing: Sequence of respiratory compromise is increased in respiratory rate initially, followed by change in respiratory pattern. Laboured open mouth breathing with development of cyanosis suggests significant compromised pulmonary function.

In both the above conditions, immediate Oxygen administration is the priority. Intra-nasal catheter is the best choice for compromised breathing patients, whereas slash tracheotomy


134

with endotracheal intubation is preferred in unconscious and apneic patients (Nasal Oxygen flow rate should be kept at 50 – 100 ml/kg/min).

C– Circulation: Hemodynamic and cellular changes that occur as a result of abnormality in circulation is referred as shock or peripheral circulatory failure.; is clinically classified in to four main categories.

Hypovolemic: occurs due to atleast 15-25 % t deficit in circulatory blood volume Cardiogenic shock: occurs due to failure of heart to pump requisite quantity of

blood in to circulation Distributive shock: due to impaired distribution of circulatory blood volume as a

result of peripheral vasodialatation Septic shock: This is endotoxin mediated shock

Therapeutic management of critically ill patient:

3. Cardio-pulmonary Resuscitation (CPR):Hallmarks of Cardio-pulmonary arrest are a) stage of apnea with cyanosis of visible mucous membranes b) absence of palpable pulse c) absence of heart sounds and d) dilatation of pupils

Guidelines for Cardio-pulmonary resuscitation

d) Positioning of animal:Lateral recumbency on small animal examination table is optimal position in small sized dogs (< 7 kgs), whereas dorsal recumbency is preferred for large sized dogs.

e) Resuscitation:Chest compression coupled with mouth to nose ventilation should be performed in patients in apneic stage.Compression rate should be 60 to 120 per minute and the compression – ventilation ratio should be 15:2. It means for every 15 compressions 2 cycles of ventilation should be performed.

4. Management of shock: Assessment of shock is governed by these parameters Pale to cyanotic mucous membranes Tachycardia with weak pulse Significant fall in Systolic blood pressure (Below 60 mm of Hg) Central Venous Pressure (CVP) less than 5 mm of H2O Elevated level of Blood lactate (> 80 mg/dl) Significant increase in Capillary Refill Time (CRT)

Therapeutic management: Emphasis should be given to

Fluid therapy:The main aim of fluid therapy is to restore circulation and improve the tissue perfusion. Choice between crystalloid and colloidal solutions should be


134

determined. Crystalloid supplements fluid along with electrolytes, whereas colloidal solutions expand the plasma volume.Commonly used colloidal solutions are: Dextran 70, Hexastarch,Gelatin polymers, Frozen plasma, Packed cell component. Commonly used crystalloids are: Normal Saline, Lactated Ringer’s solution, Dextrose Normal Saline, 7.5 % Normal saline and Hypertonic dextrose solution

Corticosteroids:Stabilization of cell membrane, blocking of arachidonic acid metabolism and gluconeogenesis are few important roles of corticosteroids in the treatment of shock Cyclo-oxygenase inhibitors:These decrease the prostaglandin synthesis and other vaso-active amines.Eg; Flunixin Meglumin( 0.25 mg/kg); Ketoprofen(0.5- 2.2 mg/kg) Antibiotic therapy in septic shock: Broad spectrum antibiotic therapy has additional advantage in endotoxin related shock. Anti-bacterials with synergistic action are also preferred in septic shock. III to IV generation ceophalosporin like cefoperazone, ceftrioxone and cefixim are frequently used in small animal practice. Control of hemorrhage and blood transfusion: Antifibrinolytic drugs are preferred to counteract extensive hemorrhage. PAMBA (Para amino methyl benzoic acid), EACA (Epsilon amino caproic acid) and Botropase have fast styptic activity Alpha Adrenergic agonist: These drugs help in improving cardiac output and thereby improve tissue perfusion. Dopamine used @ 5 – 10 µg/kg/min as constant infusion has positive ionotropic effect and increase the systolic pressure.

*****


134

MANAGEMENT OF MYCOTOXINS AND ZOOTOXINS OF VETERINARY IMPORTANCE

M.VIJAY KUMAR

Mycotoxins are the toxic metabolites released by moulds under certain conditions conducive for their growth. Acute or chronic toxicoses can result from exposure to feed or bedding contaminated with toxins that may be produced during growth of various saprophytic or phytopathogenic fungi or molds on cereals, hay, straw, pastures, or any other fodder. The principles that characterize mycotoxic diseases: the cause may not be immediately identified; they are not transmissible from one animal to another; treatment with drugs or antibiotics has little effect on the course of the disease; outbreaks are usually seasonal because particular climatic sequences may favor fungal growth and toxin production and study indicates specific association with a particular feed.

There are various types of mycotoxins and are classified as follows. Based on the causative organism: Aflatoxins - Aspergillus flavus, A. parasiticus.;Rubratoxins - Penicillium rubrum, P.purpurogenum.; T-2 toxins - Fusarium sp. F.gramaenareum and F. roseum.; Ergotoxins – Claviceps purpurea and C. paspali.Among these most common are aflatoxins. Aspergillus moulds grow rapidly when the moisture is <15%and the temperature is 24-25ºC.They commonly affect GNC, CSC, coconut cake, sunflower cake, wheat, sorghum, millets, soybean, peas and almonds.

Susceptibility:Ducks, rabbits, dogs, pigs, calves, chicken, cows, quail and sheep are susceptible in the order of preference. Broilers are more susceptible than layers. Calves are more susceptible than adult dairy cattle. Maximum allowable conc. in dairy cattle is 20 ppb (0.02 ppm)Depending on fluorescence aflatoxins are classified into B1, B2, and G1, G2. B1 is most toxic and need to be converted into its active metabolites.Toxicity is through ingestion of aflatoxin-contaminated feed. Aflatoxins are not accumulated to any appreciable extent by animal tissues with the exception of milk.

Signs:Acute - sudden death or anorexia, depression, dyspnoea, coughing, nasal discharge, anaemia, epistaxis, bloody faeces, possible convulsions and death. Subacute - jaundice, hypoprothrombinemia, haematomas and haemorrhagic enteritis. Chronic - decreased feed efficiency, decreased productivity and weight gain, rough hair coat, anaemia, enlarged abdomen, mild jaundice, depression and anorexia. Abortions may occur.


134

Postmortem Lesions: Wide spread heamorhages,Icterus,Gastroenteritis,Hepatic necrosis,Massive centrilobular necrosis,fibrosis of bile duct,Enlarged liver,Hydrothorax, Ascites,Oedema of Gall bladder wall,Pericellular cirrhosis

Diagnosis: based on History,Clinical signs,PM findings,Detection of Aflatoxin M1 in milk & urine,liver, kidney,Serum liver enzymes SGOT,SGPT,ALP elevated,Reduced prothrombin activity,Hyperbilerubinemia,Tlc,HPLC,RIA,ELISA

Differential diagnosis: Warfarin (haemorrhages), coal tar (mottling of liver) Copper poisoning (haemoglobinuria, hemolysis); Pyrrozolidine alkaloids (present in plants), CCl4, blue-green algae, crotalaria are hepatotoxic.Treatment: 1. Avoidance of contaminated feed. 2. Hydrated sodium calcium alumino silicate (HSCAS) adsorb aflatoxins @5kg /ton 3. Stanozolol (2 mg / kg) I/M decreases hepatic necrosis 4. Oxytetracycline (10mg / kg) I/M decreases hepatic necrosis.( Never administer oxytetracycline and stanzolol combination, they are mutually antagonistic) 5. Activated charcoal 6.7 mg / Kg I/R as 30% W/V slurry in M/15, PH 7 PBS(Along with charcoal,stanzolol/oxytetracycline(any one) ) 6. GSH Precursors Cysteine,methionine @2.2mg/kgi/p 7. Multi vitamins Like E,K & Selenium 8. Feeding easily digestible and low fat diet containing adequate protein

Sample collection : Samples can be taken at various stages:growing crops or during transport or storage. Whenever possible, samples should be taken after particulate size has been reduced (Ex: by shelling or grinding) and soon after blending has occurred (as in harvesting, loading, or grinding).Most effective if small samples are taken at periodic, predetermined intervals from a moving stream of grain or feed. These individual stream samples should be combined and mixed thoroughly, after which a subsample of 10 lb (4.5 kg) should be taken.. A suggested method of probe sampling is to sample at 5 locations, each 1 ft (30 cm) from the periphery of a bin, plus once in the center. This should be done for each 6 ft (2 m) of bin depth. Thus, taller bins would require more samples, and the total weight should be >10kg.

Dry samples are preferable for transport and storage. Samples should be dried at 176-194°F (80-90°C) for > 3 hr to reduce moisture to 12-13%. If mold studies are to be done, drying at 140°F (60°C) for 6-12 hr should preserve fungal activity.Containers should be appropriate for the nature of the sample. For dried samples, paper or cloth bags are recommended. Plastic bags should be avoided unless grain is dried thoroughly. Plastic bags are useful for high-moisture samples only if refrigeration, freezing, or chemicals are used to retard mold growth during transport and storage. Once a sample has been cooled or frozen, warming may induce condensation and allow mold growth.


134

Zootoxins :Out of 236 species of snakes in India, only 50 are venomous, However, the common poisonous snakes of India that man and animal come into contact, are : Cobra, Krait, Russel’s viper and Sea scaled viper, Apart from these, the other venomous snakes found in India includes Sea snakes, Pit viper and King cobra.. In animals, many a time incidence of snakes bite is near leg region and nostrils.

Sensitivity: Horse>Man>Sheep>Cattle>Goat>Dog>Pig>Cat

Venom composition: The venom compositions vary significantly among various class of poisonous snakes. Therefore, the course of toxicity as well as well as cause of death will be different, and obviously therapeutic approach will also vary. On most occasions, the identification of snake is not available or doubtful. The nature of toxicity of poisonous snakes are: Elapidae: Cobra , King Cobra, Krait- Neurotioxic; Viparidae: Russel viper- Haemotoxic; Crotalidae: Pit Viper- Neutrotoxic Haemotoxic. All the bites from venomous snakes do not lead to death due to “dry bites” which means that no venom was injected. But, some snake venoms (krait) do not have immediate effect even in a bad bite, it is wise to give veterinary/medical care.

Cobra:. identified by their “defence display” by spreading their long bones to their famous hood. ; are most active at dust, having along the wedges of agricultural fields in search of rats/mice. For this reason they live mostly in cultivated area.. The cobra venom is rich in enzymes, cardiotoxic, neurotoxic factors. The cobra venom is rich in enzyme acetylcholinesterase. Therefore, rapid depletion of acetylcholine (ACh) at neuromuscular junction occurs following envenomation. This leads to “muscular paralysis” (flacid paralysis). In addition to it, the alpha-neurotoxin is a powerful cholinoceptor blocker (nicotinic receptors). These factors hinder the function of muscles involved in respiration and consequently death occurs due to “respiratory paralysis”. It is important to identify the “big four” dangerous snakes. At first sight cobra looks like a non-venomous rat snake, but, remember that the rat snake has a pointed head and larger eyes and it can run faster.

Krait: The common krait has bluish-bluck body with white cross bands and the head is short and blunt. Kraits venom is 10 times as powerful as that of the cobra and of all the Asian snakes its venom is the most toxic (neurotoxic). Kraits are noctoural. They are active at night and rest during the day. They are found throughout India and live mostly in sandy soil in rat burrows. Their favarite hiding places are piles of wood (on bricks which provide many pray to shelter in. They are canibalistic- eat snakes, rats, lizards and birds. Famale lays eggs (10-15) and stays with them until hatch.


134

Russel viper: is a fat and bulky snake, but it can move with surprising speed when in danger. Its regular chain-like pattern and flat arrow shaped head make it easy to recognise. Its fangs are along and curved.. Venom is rich in proteolytic enzymes, hemolytic factors.

Pit vipers: are forest snakes and feed on frogs and lizards. Commonly found in coffee and tea plantations in India. Pit vipes have a small “pits” between nostrils and eyes. They are heat sensitive and can detect change in temperature when warm blooded animal comes near. Venom is not powerful and seldom results in death.

First-Aid treatment: The first aim, in case of cobra/krait bite is to retard the absorption of venom from the site of bite. ;done by applying a torniquet, provided site of bite is suitable for that. Do not disturb/ or/excite the animal with little care incise the area (1/4) and bleed. It is always better to avoid KMnO4 solution for wound wash and instead use 5% soap wash in 30 min. after bite. It is not advisible to apply torniquet in case of vipers bite as this venom is rich in spreading factors (local tissue necrosis).

Hospital treatment: The nature of hospital treatment practically depends on identity of the poisonous snake. Polyvalent antivenin is the drug of choce in the absence of identity. It is better to avoid administration of antihistaminic as they are found to increase toxic potential of certain vipers venom. Popularly, hospital treatment can be remembered as “AAA”: A = Antivenin.; A = Antibiotic (broad spectrum) andA = Antitetanus / Gas gnagrene antitoxins.

The antivenin (monovalent/polyvalent) should be administered IV at the rate of 100 ml. (small animals) or 10-50ml. (large animals). Administer antivenom with 1:00 epinephrine (0.5-1 ml. s/c) to avoid shock. Apply 1-2ml. of antivenin over the wound (site of bite in case of viper bite. Monitor the cardio vascular activity constantly. Narcotic analeptic is recommended in case of cobra bite to counteract intense pain. Epinephrine and corticosteroid to overcome hypotension and shock. Employ plasma volume expander (6% dextran-40) and calcium gluconate to reduce hemolysis. In case of viper bite, even if the patient survive, amputation may be performed to avoid spread of local tissued necrosis or gangrene formation.

Note: - Anitivenom should be stored at 40C. Do not administer if they are discoloured or after the date of expiry.

*****


134

CLINICAL CONSIDERATIONS IN ADVERSE EFFECTS OF DRUGS

U. SUNILCHANDRA

Adverse drug effects includes all adverse /side effects associated with a drug; including that observed in overdose/poisoning with drugs or effects that may occur during therapy. The mportant adverse effects of the drugs, in general are discussed in this article.

Drug allergy/ hypersensitivity : Most common drug allergens implicated in producing anaphylactic reactions in domestic animals include penicillins, cephalosporins, sulfonamides, streptomycin, tranquliisers, vancomycin, vitamins, insulin, tetracyclines, quinolones, salicylates, phenothiazines, chloramphenicol, heoparin, lidocaine, erythromycin, angiotensin converting enzyme inhibitors, methyl dopa, vitamin K, iron injections, exogenously administered repeated injections of

hormones(LH,hCG,PMSG),thiopentone, suxamethonium,non-depolarising muscle relaxants, ester local anaesthetics and plasma expanders (dextrans, starches and gelatins). Other agents that can cause anaphylactoid reactions include vaccines, food and insect stings.

Clinical signs are manifested by the involving various organ systems.Cardiovascular system:hypotension and cardiovascular collapse. tachycardia, arrhythmias, cardiac arrest.; Respiratory System :oedema of the glottis, tongue and airway structures may cause stridor and airway obstruction. Bronchospasm - may be severe.; Gastrointestinal: abdominal pain, diarrhoea or vomiting.; Haematological.: coagulopathy. ; Cutaneous : flushing, erythema, urticaria. signs may be seen. Adrenaline (1:1000 epinephrine) is the most useful drug for treating anaphylaxis as it is effective in bronchospasm and cardiovascular collapse. The dose of 0.01ml/kg.IV or 0.2 – 0.5ml/kg, IM is repeated in 10-15minutes if clinical signs are not resolving. Ensure adequate breathing. Intubation and ventilation may be required.Venous return may be aided by lifting the patient's legs or tilting the patient head down Antihistamine agents: H1 blockers and corticosteroids are also administered


134

Hepatotoxicity : Drug-induced liver damge is manifested by highly variable, ranging from asymptomatic elevation of liver enzymes to fulminant hepatic failure. The type of drug induced hepatotoxicity is often accompanied by fatigue, fever, and rash, usually developing after few weeks of therapy. The clinically important potential hepatotoxic drugs: acetaminophen,amoxicillin,chlorpromazine,ciprofloxacin,diclofenac,erythromycin,fluconazole, isoniazid,methyldopa,rifampin, tetracycline,phenobarbitone, phenytoin, primidone,diazepam (in cats), mebendazole, carprofen, diethylcarbamazine, oxibendazole, sulfonamides, anabolic steroids, vincristine etc. Treatment is to discontinue the suspected drug. Specific therapy against is limited to the use of N -acetylcysteine (acetaminophen toxicity) and L-carnitine( valproate toxicity).

Nephrotoxicity:

The most common drugs with nephrotoxic potentiality are aminoglycosides, NSAIDs, sulfonamides, tetracyclines, amphotericin B, antiviral agents, methotrexate, the older

cephalosporins, cimetidine, ciprofloxacin, furosemide, penicillins, phenytoin, rifampin, thiazide diuretics, polymixin etc. Crystalluria, hematuria and obstruction of renal tubules occurring with sulfonamides are prevented by adequate water intake during the therapy and alkalinisation of the urine with urinary alkaliser (eg: sodium bicarbonate) supplementation. The prevention or minimizing the drug induced nephrotoxicity is by administering single daily dose; reducing the treatment course ; avoiding concurrent administration of other nephrotoxic drugs or reducing the doses in conditions of renal insufficicency/impairment.

Drug interactions:. may lead to diminished or an enhanced effect of a drug or may lead to toxicity. Some pharmacodynamic drug interactions include : GC and NSAIDs (increased gastrointestinal toxicity), furosemide and ACE inhibitors (increased diuretic effect), sucralfate and gastric acid secretion inhiobitors( decerased efficacy of sucralfate), NSAIDs and anticoagulants(increased bleeding), opioids and general anaesthetics(enhanced respiratory depression by opioids) etc.

Some pharmacokinetic drug interactions that may affect negatively the absorption of the administered former drug include: fluoroquinolones with cations Na+ and Cl-. Al and Mg,, Orally active penicillins with antacids, tetracyclines with milk, antacid, laxatives, digitalis with phenolphthalein (laxative), erythromycin with anti-cholinergic drugs, linocomycin with kaolin, and orally administered antibiotics with large dose of atropine. The examples of pharmacokinetic drug interactions during metabolism: phenobarbital with griseofulvin(decreasedefficacy),chloramphenicol(decreasedefficacy),primidone/


134

phenytoin(increasedhepatotoxcity),corticosteroids(decreased efficacy);fluoroquinolones with theophylline (theophylline toxicity-CNS stimulation) etc.

Teratogenicity: Typical manifestations include congenital malformations( birth defects), intrauterine growth restriction, carcinogenesis and fetal demise. Interference in the formation process of major body structures(first 12 weeks of conception) cause teratogenic effect.Classes of teratogens include radiation, maternal infections,chemicals,and drugs Cytotoxic drugs (antineoplastic drugs),anticoagulants(warfarin),vitamin A analogues (etretinate, isotretinoin), anticonvulsants(carbamazepine,phenytoin,sodiumvalproate),Cardiovasculardrugs(Angiotensin-convertingenzymeinhibitors,AngiotensinIIinhibitors,losartan,spironolactone), Endocrinological drugs (carbimazole,propylthiouracil,chlopropamide, sulphonylureas), Antifungaldrugs(griseofulvin,ketoconazole,triazolesfluconazole,itraconazole,terbinafine),cardiovasculardrugs(betablockers,minoxidil),Antiinflammatorydrugs(NSAIDs;3rdtrimester),antibiotics(tetracycline,ciprofloxacin, chloramphenicol, nitrofurantion, vancomycin, aminoglycosides), antihelminthics (mebendazole,albendazole, oxfendazole) and others ( misoprostol ,statins). Before using a drug, consideration must be given to any potentially harmful effects on the fetus or mother. To minimize the fetal risks, the lowest possible effective dose should be used. Antineoplastic drugs, radio isotopes and oestrogens are the potential carcinogens and mutagens.

CNS disturbances:. Antibiotics to avoid, or use with care in patients with seizures include enrofloxacin, cephalosporins and penicillins (in renal disease), and imipenum. Metronidazole in higher doses; more common in cats. Ivermectin (related drugs -milbemycin, moxidectin), loperamide and vincristine are expelled from the CNS by p-glycoprotein. Collies, Shetland sheepdogs, English sheepdogs, and Australian shepherds are susceptible to these drugs when administered at normally therapeutic concentrations. The other common drugs with potentiality of CNS disturbances: levamisole,tetramisole,loperamide,tinidazole,metoclopramide,promethazine, prochlorperazine, terbutaline,chlorpromazine, methylxanthines, piperazine, respiratory stimulants (doxapram,nikethamide)and antihistaminics (sedation,also possible), all of which may result in transcient CNS stimulation depending on the dose and condition.

Photosensitization: Photosensitivity reactions or photosensitization is a clinical condition in which skin (areas exposed to light and lacking significant protective hair, wool, or pigmentation) is hyperreactive to sunlight due to the presence of photodynamic agents. Tissue injury is thought to result from the production of reactive oxygen intermediates or from alterations in cell membrane permeability. It is most commonly seen in cattle,sheep,goats,and


134

horses.Tetracyclines,fluoroquinolones,sulophonamides,antihistaminics,diuretics(thiazides,loop),tricyclicantidepressants,phenothiazines and corticosteroids are examples of drugs with phototoxic potentiality. Photosensitive animals on prolonged exposure to sunlight- scratch or rub lightly pigmented, exposed areas of skin (ears, eyelids, muzzle), inducing typical skin lesions : erythema, edema, serum exudation, scab formation, and skin necrosis . In cattle, and especially in deer, exposure of the tongue while licking may result in glossitis, ulceration and deep necrosis. Treatment involves palliative measures (steroids, topical antibiotic)

Gastrointestinal disturbances: manifested by nausea, vomition, diarrhoea, abdominal pain are most commonly observed after the oral administration of macrolides, tetracyclines, piperazine, cephalosporins, oxyclozanide, fluoroquinolones, penicillins, nitrofurans, rafoxanide, NSAIDs, sulphonamides, antineoplastic drugs. Unless severe as in case of anticancerous drugs, most of them are transcient and are self limiting.

Local pain, tissue injury and irritation :. Bleeding from the injection site and hematoma formation can occur if blood vessels are injured during particularly intramuscular injections.. Skin necrosis, neurological damage, and loss of limb can follow. The sciatic nerve is commonly injured by gluteal IM injections and the radial nerve injury at the shoulder, commonly manifested by paresis, necrosis etc. Numerous drugs like quinpyramine salts, suramin, diminazine, b complex injectables, multivitamin injectables,cephalosporins, tetracyclines, NSAIDS, oil based injectables, the long-acting injectable medications may result in complications at IM injection sites. The extravasation of anticancerous drugs outside the vein may result in thrombophlebitiis and tissue necrosis.

*****


134

COMMON HOUSEHOLD SUBSTANCES OF TOXIC POTENTALITY

U. SUNILCHANDRA

Household products being formulated as complex chemical mixtures with multiple active ingredients designed for specific applications may be hazardous to pets and children with accidental exposure.The common route of exposure of the household hazardous compounds may be dermal, oral, ocular or inhalational. Some of the important indoor substancse with higher toxic potentiality are described especially with reference to pets.

SOAPS AND DETERGENTS: This class include soaps,shampoos, spray cleaners, dishwash liquids , powders, laundry products, disinfectants, fabric softeners and sanitizers. Bath soaps and bar soaps usually have low toxic potential, causing mild gastroenteritis with vomition, on ingestion. Demulcents and diluents: milk , rinsing with water for dermal and ocular exposure; Induction of emesis if soap is non alkaline( noncorrosive), if there is no spontaneous vomition within thirty minutes of ingestion and, fluid and electrolyte therapy.

Nonionic detergents ( alkyl ethoxylate; sources: shampoos, dishwash detergents,laundry detergents) generally have low order of 219oxicoses219 and toxicity, being non corrosive. Anionic (alkyl sodium sulfonate, dioctyl sodium sulfosuccinate, sodium lauryl sulfate; sources: shampoos, dishwash detergents, laundry detergents) and cationic ( benzalkonium chloride, ,cetirimide; sources: fabric softeners, germicides, disinfectants, sanitizers) detergents (Quaternary ammonium compounds) are corrosive and highly toxic. Ethanol and isopropanol, often found in cationic detergents ;enhance gastrointestinal absorption and damaged skin favours percutaneous absorption.

Toxicity related clinical signs are vomition, diarrhoea, gastrointestinal discomfort, intravascular hemolysis in impaired liver condition, dermal irritation, corneal damage ; Oral-corrosive damage, salivation,muscle weakness, respiratory and CNS depression, seizures, collapse, comapredominantly seen with cationic detergents. Treatment involves dilution with milk, water, egg white, administering act.charcoal, saline cathartics, fluids, antibiotic, analgesics and thorough washing the skin with soap and water and eye lavage with isothermic isotonic saline for 20minutes.

CORROSIVES :. Acidic corrosive (Hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, sodium bisulfite) product examples are antirust compounds, toilet bowl cleaners, automobile batteries, gun barrel cleaning fluid and swimming pool cleaning


134

agents. Alkaline (sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonium hydroxide, potassium permanganate) product examples are drain cleaners, washing products, liquid cleansers and toilet bowl products. On dermal and ocular exposure: serious burns, extremely painful, corneal/conjuctival necrosis, perforation and opacity. On ingestion: corrosive burns of mucosal membranes ( milky white/ grey, turning to wrinkled black). Vocalization,depression,,panting, inability to swallow.haematemesis, abdominal pain, polydypsia, respiratory distress, shock, secondary pneumonia from aspiration of vapours, gastrointestinal bleeding, perforation and fistula are the other signs observed depending on the severity. Oral dilution with egg white , milk or water, skin and eyes thourghly flushed with copious water and sterile saline respectively; therapy for shock: IV fluids, steroids within 48 hours, which reduce the fibroblastic activity and inflammation, reduce the stricture from circumferential alkaline burns. Analgesics and antibiotics prophylactically in animals with perforations. Attempts to neutralize burns chemically(as exothermic reactions produce elevated local heat and thermal burns), gastric lavage, induction of emesis are contraindicated. . Charcoal is ineffective in binding to caustics.

DISINFECTANTS: found in cleanimg products include quaternary ammonium compounds, phenol, pine oil, bleaches, alcohols; are more toxic than soaps and detergent compounds

Phenols: highly reactive,corrosive contact poisons; denatures and precipitates cellular proteins of all contacting cells. nephrotoxic, hepatotoxic and neurotoxic; rapidly absorbed through ingestion, inhalation or skin. Cats are highly sensitive. Sources of phenolic compounds: flooring materials, coal tar, creosote, tar paper. It results in intense pain, areas of coagulative necrosis; treated by glycerol, polyethylene glycol washing, thorough rinsing with water , dressings soaked in 0.5% soda bica. Also may cause corrosive burns of mouth, oropharynx, oesophagus. Vomition, salivation,ataxia, panting, weakness, tremor, coma, seizures, methhaemoglobinaemia, respiratory alkalosis, severe liver and kidney damage. Demulcents-milk, egg white, gastric lavage and emesis(contraindicated if severe damage) activated charcoal, saline cathartic, 1% methylene blue, 4mg/kg;IV; ascorbic acid 20mg/kg,PO; N-acetyl cysteine 140mg/kgIV, 70mg/kg PO. Q,id for 3 days. Ocular exposure is treated by sterile saline wash.

Bleaches: preparations contain sodium hypochlorite.Calcium hypochlorite and trichloroisocyanuric acid are present in industrial strength bleaching solutions ,swimming pool chlorine products and chlorine laundry bleaches. Non chlorine bleach preparations or colorfast bleaches contain sodium peroxide, sodium perborate or enzymatic detergents. Generally, the toxicity of bleaches is of lower degree, resulting in irritation of


134

ropharynx, salivation, vomition and abdominal pain. Bleaching of hairs, pulmonary irritation- coughing , dyspnoea and retching on inhalation may also be seen. Nonchlorine bleach products, (sodium perborate, sodium peroxide) are alkaline and severe gastric irritatants causing renal damage and CNS excitation, depending on the amount ingested.

Treatment: Milk and water orally; washing with soap and rinsing with abundant water/sterile saline on dermal/ocular exposure. Induction of emesis and orogastric lavage is contraindicated to avoid the risk of causing further oesophageal irritation. Milk of magnesia (2-3ml/kg) can be administered and other clinical signs are treated symptomatically.

Deodorants: composed of aluminum chloride and aluminum chlorohydrate; which have moderate toxicity potential. Ingestion can cause oral irritation, necrosis, gastroenteritis and nephrosis.; which can be treated by orogastric lavage, antiemetics and gastroprotectant drugs.

SOLVENTS AND ALCOHOLS: The most commonly encountered solvent (acetone: sources: nail polish remover, varnishes, glues )and alcohols include isopropanol(perfumes,cologne, grooming products), methanol (antifreeze products, automotive wind shield clesnser, consumer products) and alcohol (alcoholic beverages, cosmetics, mouthwashes ,common baker’s and brewer’s yeast). Activated charcoal is ineffective in binding to the alcohols, not to be used. Clinical signs noticed are CNS and respiratory depression acidosis, ataxia, hypothermia, cardiac arrest, coma; which is treated by emesis induction, (if < 2 hrs); IV fluid Ringers lactate/ saline solution with NaHCO3(1-3mEq/kg). Ethanol reduce severity of methanol poisoning.

Petroleum distillates: The compounds include cyclohexane, alkanes and alkenes. Sources: gasoline (petrol), kerosene, motor fuels, solvent paints and vehicles for pesticides. Because of low surface tension, chance of aspiration is most common. Dermal exposure may result in dermatitis. Oral exposure results in aspiration pneumonia, cough, hyperthermia, cyanosis, CNS depression and pulmonary oedema.. Emetics and oily purgatives are contraindicated, as they increase the risk of aspiration. Gastric lavage and activated charcoal should be reserved for ingestion of large amount(2ml/kg) or when other toxicants are present. Oxygen therapy, rest , flushing the skin and eyes with water and IV fluids to maintain hydration and electrolyte balance is recommended. Other solvents (eg: acetone, turpentine) or other hydrocarbons should not be used for removing the petroleum distillates from skin.


134

BATTERIES : Automotive or dry cell batteries contain sulfuric acid, that can be irritating on contact with eyes, skin and gastrointestinal tract., which is treated accordingly as with acid exposure.The sources of small disc/button batteries include batteries used in calculators, cameras, hearing aids, watches , the content being mainly mercuric oxide. The dry cell batteries , commonly used in toy flash lights, may contain the alkaline ( NaOH, KOH; alkaline batteries) or acidic compounds (ammonium chloride, manganese dioxide, heavy metals- Li, Ni, Zn, Ag, Cd) in them. On ingestion, most of the intact batteries pass through digestive tract within 24 to 36 hours without producing any major adverse effects, except for mechanical obstruction occasionally. Gastrointestinal distress may occur resulting from retention and obstruction, which has to be diagnosed by radiography and has to be corrected by endoscopy and surgery . If battery is chewed and split apart, it may cause corrosive damage depending on the chemical content in it. Timely surgical intervention together with the administration of saline cathartics, enemas and appropriate chelation therapy with specific chelating agents if any (eg: DMSA or D-Penicillamine as for Pb), can minimize the corrosive damage caused. Lead is the major source of toxicity among the metals, resulting in acute or chronic toxicity upon ingestion. The sources of lead are paints, batteries, solder, plumbing supplies, lubricating material, ceramic containers, Pb pipes, toys, inks, dyes, used oil from vehicles that burn leaded gasoline. The clinical signs noticed are Acute- CNS excitability signs, convulsions, behavioural changes, ataxia, tremor, blindness. Chronic-gastrointestinal disturbance signs, vomition, pica,diarrhoea, abdominal pain. Treatment is by administering Ca disodium EDTA, 25mg/kg, q.i.d, SC diluted in 10% dextrose ,Oral D-penicllamine, 110mg/kg/day, 1-2 weeks, Dimercaptosuccinic acid(DMSA), 10mg/kg,t.i.d.

CYANOACRYLATE ADHESIVES ( SUPERGLUE) : Uncured cyanoacrylate adhesives form an almost instantaneous bond on contact with hair/skin resulting in annoyance and frustration of the animal. Cured ones are nontoxic upon ingestion .Dermal exposed areas are soaked with warm soapy water as quickly as possible. and with acetone for several minutes, if area is away from face or eye. The hairs may be clipped to reduce the tension on skin. The surfaces should not be pulled apart, with direct opposing actions.Ocular : Eyelid/eyeball is thoroughly washed with warm water and Elizabeth collar is applied to prevent self trauma. The animal will be able to open eyes on its own with no residual tissue damage within 2-3 days and hence forceful manipulation should not be done.

Methylxanthines: Sources: Coffee, tea, chocolates, cola/soft drinks, asthma, analgesic,cold medications. Caffeine, 222oxicoses222is and theobromine are the primary


134

toxic agents. Clinical signs manifested by vomition, diarrhoea, polyuria, weakness, hyperexcitability, tremors, seizures, coma and death resulting from cardiac tachyarrhythmias. If ingestion is less than 2 hours, emetics administration followed by, activated charcoal and saline cathartic is indicated. Since methylxanthines undergo enterohepatic recycling, charcoal should be administered every 3-6 hours until symptoms disappear. Antiarrythmics (lidocaine, without epinephrine; 1-2mg/kg,IV- loading dose; 40-60mg/kg/min infusion rate, slow IV- as maintenance dose) or beta blocker (metoprolol; 0.1- 0.3mg/kg,PO,tid) to control arrhythmia;Diazepam or phenobarbitol to control seizures and fluid therapy to maintain hydration and electrolyte balance is recommended. Corticosteroids and erythromycin should be avoided as they decrease urinary excretion of methylxanthines.

Aspirin : Clinical signs of aspirin toxicoses in cats are dose-dependant and may include CNS depression, anorexia, vomiting, gastric hemorrhage, 223oxicoses223is , toxic hepatitis, anemia, bone marrow hypoplasia, hyerpnea and hyperpyrexia, hyperthermia, hyperglycemia, and glycosuria. Treatment is by GI decontamination with emetics, activated charcoal and cathartics, within 4 hours of ingestion. Acid-base imbalance is corrected with a slow infusion of sodium bicarbonate, carefully monitored and adjusted to avoid pulmonary edema being developed. The resulting hyperthermia should be controlled by external cooling; the use of antipyretic drugs should be avoided.

Paracetamol: Toxicity Signs: Dirty brown colored gums, dyspnoea, haematuria, jaundice ,facial and paw edema , cyanosis, hypothermia, and vomiting. Less common signs include coma, generalized weakness, and death. If ingestion is less than 2 hours, emetics, activated charcoal and saline or osmotic cathartic are indicated.. If severe cyanosis is present, oxygen therapy should administered, and the animal should be subject to as little stress as possible.IV Administration of acetylcysteine, 140mg/kg/hr for 7 hours; Ascorbic acid, 30 mg/kg orally to reduce methemoglobinemia to Hb. Supportive care including fluid therapy for possible metabolic acidosis is also recommended.The other drugs used for NSAID 223oxicoses include ranitidine(2mg/kg,tid,IV,PO),omeprazole(0.7mg/kg,sid,PO),metoclopramide(0.2-0.4mg/kg, tid,PO,IM), sucralfate (0.5-1g, bid,PO)and misoprostol(2-5µg/kg,tid,PO)

Xylitol: is a sweetener used in sugar free products/chewing gums;induces hypoglycaemia by stimulating insulin secretion , resulting in weakness,m ataxia, seizures and collapse. Therapy: Inducing emesis administering activated charcoal, 50% dextroseIV and liver tonics


134

Amitraz: poisoning occurs commonly from ingestion of a tick collar. Clinical signs include ataxia, bradycardia, CNS depression, vomition, diarrhoea, and seizures. Treatment involves decontamination (emesis, activated charcoal, saline cathartic) and repeated injections of yohimbine (0.1mg/kg.IV) or atepamizole to reverse its adrenergic agonistic effects and atropine has to be avoided as it may increase the absorption.

*****


134

PHARMACOLOGICAL MANAGEMENT OF BEHAVIOURAL ABNORMALITIES IN ANIMALS

U.SUNIL CHANDRA

The majority of the drugs prescribed for behavioral problems in pets are unlicensed and not registered for veterinary use and are used in an extra-label fashion., with few exceptions . Clients must be made aware of this and informed consent forms should be obtained before initiating the treatment. The client cooperation over administration of these drugs is an important consideration as many of the drugs take a considerable time to produce desirable effects on the animal, requiring relatively long term administration (weeks to months). Drugs should always be considered as an adjunct to behaviour modification therapy, not as a replacement/ substitute. Client compliance is important as behaviour modifying drugs may take up to six to eight weeks to reach therapeutic blood concentrations. Drug therapy should always be gradually withdrawn.. An overview of the classes of medications used in behavioural abnormalities of dogs and cats are described in this article.

Benzodiazepines ( BZDs): The agents are oxazepam, clorazepate, lorazepam, temazepam, clonazepam, diazepam and alprazolam, the last two being most commonly indicated for treatment of anxiety related behaviour problems like urine spraying and short treatment for sound phobias (eg: fireworks, thunderstorms). Diazepam produces short-term anxiolytic effects and at low doses diazepam retains its amnesic effects, while at higher doses anxiolysis and sedation are achieved. Responses to diazepam are highly individual, so that dose response must be titrated. Diazepam should be given prior to an anticipated fearful or phobic event.Adverse effects of ataxia, hyperexcitability and disinhibition. Alprazolam may also be used in advance or given after a phobic event in order to impair the dog’s memory of it. It may therefore be used to block the effects of unanticipated phobic events in order to prevent them from having an emotional impact on the animal in the future. BZDs are contraindicated in states of hepatic and renal impairment and for long term use in cats.

Monoamine oxidase inhibitors(MAOIs): Selegiline is used for the treatment of behavioural disorders with an emotional origin, which includes fears and phobias. It reduces fearfulness, increases exploratory behaviour and has positive effects on cognition even in healthy animals. It takes 4-8 weeks to begin to become effective, and is a useful adjunct to behavioural therapy, especially in individuals that are frequently exposed to noise


134

events, show signs of a generalisation or are inhibited in situations when they are fearful or anxious

Tricyclic antidepressants (TCAs): Clomipramine and amitryptilline are the TCAs licensed for use in veterinary medicine., commonly used for separation anxiety, anxiety-related aggression, urination due to submission or excitement, allergy-related pruritus, urine marking and hypervocalization. The most common side effects are short term lethargy or sedation, mild and intermittent vomiting which is usually transient and increases or decreases in appetite. The antihistaminic effect of these agents may be a useful adjunct in controlling pruritus due to atopy and food allergies. They are contraindicated in animals with seizures, urinary retention or history of cardiac arrythmias and within two weeks of administration of a MAOI

Selective Serotonin ReUptake Inhibitors (SSRIs): Fluoxetine, sertraline and fluvoxamine are used for treating psychogenic alopecia, allergy-related pruritus, anxiety related conditions, dominance-related aggression, fearful behaviors, obsessive-compulsive behaviors, and urine marking. Fluoxetine is approved drug in dogs, for inter-dog aggression and the treatment of obsessive-compulsive disorders in dogs. It reduces the clearance of diazepam, its active metabolite nordiazepam and alprazolam, so concurrent use should be avoided.

Azapirones: Buspirone is the only member, advocated for treatment of mild to moderate anxiety related problems and urine spraying in dogs and cats. Contraindicated in case of renal, hepatic impairment, epileptics, allergic reactions and caution is needed as treatment can lead to an increase in aggression as it may decrease the inhibitory effects of fear. It is ineffective in cases such as sound phobias or separation anxiety in dogs.

Beta blockers: Porpranolol and pindolol are, indicated in treatment of situational anxieties in dogs and cats, used before the anticipated situation occurs. They are contraindicated in animals with cardiac disease, hypotension, and bronchospasm.

Hormonal preparations: Progestins should only be given to neutered animals and avoided in diabetes mellitus, breeding animals and with concurrent corticosteroid use. The antiandrogen commonly used is delmadinone acetate. Cabergoline has antiprolactin effects and is recommended for the treatment of pseudopregnancy in bitches and in spayed bitches with aggressive behaviour attributable to elelvated prolactin levels.

Antihistamines: They are useful in the management of mild anxiety associated with travel, inappropriate night time activity and anxiety conditions in which pruritus plays a important role. They are contraindicated in animals with glaucoma,urinary retention and


134

hyperthyroidism.Diphenhydramine(0.4 - 0.5 mg/kg po bid-dog; 2-4mg/cat bid-tid-cat) and Cyproheptadine (0.4 - 0.5 mg/kg po bid-dog; 2 - 4mg/cat bid-tid-cat) are the H1receptor antagonists that are successful in some cases of spraying in cats.

Alpha adrenoceptor stimulants: Phenylpropanolamine (1.1-4.4 mg/kg,po,bid )used in the treatment of sphincter mechanism incompetence in bitches and used to manage house soiling in these cases. Increased aggression is the possible side effect.

Alpha adrenoceptor antagonists: Nicergoline (250-500 µg /kg,po,sid) is advocated for sleep disorders, diminished vigour and fatigue. It should not be administered within 24 hours of using alpha 2 agonists such as xylazine or medetomidine.

Xanthine derivatives: Propentofylline is licensed for canine age related behavioural changes such as dullness, lethargy and cognitive decline,which respond better if combination therapy with selegiline is used.

Neuroleptics (Antipsychotic agents): Low potency phenothiazine tranqillisers (acepromazine, chlorpromazine, and thioridazine hydrochloride) commonly used for sedation and restraint purpose, have side effects of sedation, anticholinergic effects, and α-adrenergic blockade. High-potency agents (haloperidol, fluphenazine, trifluoperazine hydrochloride, prochlorperazine, thiothixene, risperidone) result in less sedation and fewer autonomic side effects but commonly result in extrapyramidal effects.Acepromazine is used as a short-term tranquilliser during phobic events related with fireworks and thunderstorms and travel associated behaviour problems. It is believed that immobilising an animal whileleaving it aware of, and emotionally responsive, to a phobic event may intensify the experience and lead to worsening of phobia in the future. High doses which may be required in order to sedate a dog; may result in hypovolaemia, hyperexcitability and extrapyramidal side effects.

Dosage , route and frequency of administration of drugs used in behavioural abnormalities of dogs and cats

BZDs: DOGS:Diazepam(0.55 -2..2 mg/kg po sid-bid); Alprazolam (0.01-0.1mg/kg,PO,bid),Oxazepam (0.2 – 1.0 mg/kg po sid-bid), Clonazepam (0.1 - 0.5 mg/kg po sid-bid),Clorazepate(0.01-0.1 mg/kg po,bid). CATS: Diazepam(0.2 - 0.4 mg/kg po sid-bid); Alprazolam (0.125 - 0.25 mg/cat po bid),Oxazepam (0.2 - 0.5 mg/kg po sid-bid), Clonazepam (0.016 mg/kg sid-qid),Clorazepate(0.125-0.25 mg/kg po bid .

TCAs: DOGS: Amitriptyline (1-2mg/kg,po,bid),Clomipramine (1-3mg/kg,pobid), Nortriptyline( 0.5 - 1.0 mg/kg posid-bid), Doxepin (3-5mg/kg.po,bid); CATS: Amitriptyline


134

(0.5 - 1.0 mg/kg po sid),Clomipramine (0.25 - 0.5 mg/kg po sid), Nortriptyline (0.5 - 1.0 mg/kg posid-bid), Doxepin (0.5-2.0mg/kg/po,bid).

SSRIs: DOGS: Fluoxetine(0.5-1mg/kg,po,sid),Fluvoxamine (1-2mg/kg,po,sid),Sertraline(1-2mg/kg,po,bid), Paroxetine (1mg/kg, po, sid) ; CATS: Fluoxetine(0.5-1mg/kg,po,sid),Fluvoxamine (1-2mg/kg,po,sid),Sertraline(1mg/kg,po,bid.

MAOIs: Selegiline-0.5-1mg/kg, po,sid-dogs,cats; Azapirones: Buspirone-0.5-1mg/kg,po,bid,(< 5mg/cat

Beta blockers: Propranolol-0.5-3mg/kg,po,bid-dogs; 0.2-1mg/kg,po,bid-cats; Pindolol -0.125-0.25mg/kg,po, bid (dog); Dopamine2 receptor agonists: Cabergoline-5 mg/kg,po,sid-dog

Antiepileptics: Phenobarbitone -1-8mg/kg,po,bid (dog) 1-2.5mg/kg,bid (cat); Carbamazepine-4-8 mg/kg,po,bid (dog); Total 25mg, po,bid (cat)

Xanthines: Propentofylline- 2.5-5 mg/kg,po, bid (dog); otal dose-12.5mg, po, sid (cat)

Progestins: Megestrol Acetate - 2.5 - 5 mg po sid (dog); 2.5 - 5 mg po sid (cats); Medroxyprogesterone Acetate10 mg/kg(female) ;20 (male) SC – max : 3 injections per year (dog); 10(females); 20 (males) mg/kg, sc – max. 3 injections per year (cat)

po=oral, IV=intravenous, SC=subcutaneous, bid= twice a day, tid=three times a day, sid= once daily

*****


134


134

DIAGNOSTIC TESTS FOR DETECTION OF COMMON TOXICANTS IN SAMPLES

M.VIJAY KUMAR

Detection of Heavy metals: Place 10g of tissue (finely minced) in a beaker or test tube.Add 10 ml of 10% HCl.Introduce a copper wire into the test tube Boil for 10-15 min. (Do not inhale fumes) Remove the copper wire and place it on a filter paper Observe the colour of the copper wire. Inference: Black coloration - Arsenic or Bismuth; Shining silver deposit – Mercury; Dull white deposit – Silver; Dark colour with purple to blue; violet green - Antimony.

Depending on the colour of copper wire the confirmatory test is conducted.If the deposit is black it can be confirmed whether it is due to arsenic or bismuth by placing the copper strip in 1-2 ml. of 10 % potassium cyanide. If the deposit is due to arsenic, it will dissolve, but if it is due to bismuth or antimony, it will persist.In mercury, colour of the deposit ranges grayish (50 mg) to shiny silver (100 mg).

Detection of lead : Mince the liver/kidney piece or collect a small amount of scraping from stomach wall.Add a few drops of conc. nitric acid and heat gently till dry, (never over heat the sample as it turns black making reading difficult). Add a few drops of water and two drops of 10% pot. iodide solution.Development of yellow colour indicates presence of lead.

Detection of Cyanide: a) in biological material: Take 50 g of finely ground tissue or stomach contents in a 100 ml flask and acidify thecontents with tartaric acid. Take a filter paper previously moistened with 10 % of guaiacol in alcohol and 0.1% of aqueous copper sulfate solution.Plug the mouth of flask and warm gently. Allow it to stand for 30 minutes. Observe the colour of paper. If cyanide is present, a blue colour develops.

b) in the plant sample: Preparation of sodium picrate paper-Dissolve sodium bicarbonate 5 g and picric acid 0.5 g in 100 ml of distilled water. Cut filter paper into strips of 2. x 6. size. Dip the strips in the reagent and dry in cool place.

Take the given sample in a test tube and add a few drops of water and chlorofom. Plug the test tube with cotton, hanging the dried picrate paper inside the test tube. The paper should not touch the fluid in the tube. Heat the tube gently till fumes evolve. Observe the colour of paper.If the colour of paper changes from yellow to brown it indicates that the


134

plant sampleis positive for cyanide.(The leaves and stomach contents are to be frozen immediately after collection inpolythene bag as CN is likely to evaporate).

Detection of fluorides: To a small quantity (1-3 ml) of urine or stomach contents add 3 ml of sodium hydroxide solution in a glass or porcelain dish. Add a little quantity of powdered glass and mix thoroughly. Apply moderate heat till dry. Add 10 ml of concentrated sulfuric acid and cover the dish with a small plate from the under surface of which is suspended a drop of 5% sodium chloride solution. Place a small piece of ice on top of the plate to prevent evaporation of the drop. Heat gently for 3-5 min., carefully remove the drop and examine under low power of microscope. If the given specimen contains fluorides, silicon fluoride is formed which appears as small light pink hexagonal crystals along the rim of the drop, whereas the crystals of sodium chloride are large and square.

Detection of Nitrite: a) Draw blood (10 ml) without anticoagulant from an affected animal and also from a known normal animal in 20 ml capacity test tubes.Place them in boiling water bath for 45 minutes. Cool them.Observe the colour of the blood and the surface.Blood sample containing nitrite is Salmon pink in colour, does not pull away fromthe side and the surface is level or concave. Normal blood sample is chocolate brown,pulls away from the side of tube and the surface is convex.

b)In a plant sample: Dissolve 0.5 g of diphenylamine in 20 ml of distilled water and make up the volume to 100 ml with sulfuric acid. Store it in amber colored bottle. This is a full strength solution and can be made into half strength by diluting with equal parts of 80% sulfuric acid. To test a plant, place a drop of the reagent on the cut surface of plant. Observe the colour.A green to blue colour indicates the presence of nitrate.(A green to blue colour with a half strength solution indicates positive (++) for nitrate, which could be toxic to animal).

*****


Advances in Veterinary Antimicrobial Therapy and Forensic Toxicology

Documents

Transcript of Advances in Veterinary Antimicrobial Therapy and Forensic Toxicology