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PHYSIOLOGY OF VITAL ORGANS: A REVIEW

SHRIKANT KULKARNI

The knowledge of basic physiology of alla the vital organs is very much essential inorder to effecly achieve the therapeutic protocols and also to understand the pathological changes that are taking place in body of the patient.The following description is an attempt to revise the basic physiology of important vital organs in the body.

BRAIN:

The brain is the center of the nervous system and is a highly complex organ. Enclosed in the cranium. In spite of the fact that it is protected by the thick bones of the skull, suspended in cerebrospinal fluid, and isolated from the bloodstream by the blood-brain barrier, the delicate nature of the brain makes it susceptible to many types of damage and disease. The most common forms of physical damage are closed head injuries such as a blow to the head, a stroke, or poisoning by a wide variety of chemicals that can act as neurotoxins. Infection of the brain is rare because of the barriers that protect it, but is very serious when it occurs.

The most important biological function of the brain is to generate behaviors that promote the welfare of an animal. Brains control behavior either by activating muscles, or by causing secretion of chemicals such as hormones. Even single-celled organisms may be capable of extracting information from the environment and acting in response to it. However, sophisticated control of behavior on the basis of complex sensory input requires the information-integrating

Several brain areas have maintained their identities across the whole range of vertebrates, from hagfishes to humans.

The medulla, along with the spinal cord, contains many small nuclei involved in a wide variety of sensory and motor functions.

The hypothalamus is a small region at the base of the forebrain, whose complexity and importance belies its size. It is composed of numerous small nuclei, each with distinct connections and distinct neurochemistry. The hypothalamus is the central control station for sleep/wake cycles, control of eating and drinking, control of hormone release, and many other critical biological functions.

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The thalamus is a collection of nuclei with diverse functions. Some of them are involved in relaying information to and from the cerebral hemispheres. Others are involved in motivation. The subthalamic area (zona incerta) seems to contain action-generating systems for several types of "consummatory" behaviors, including eating, drinking, defecation, and copulation.

The cerebellum modulates the outputs of other brain systems to make them more precise. Removal of the cerebellum does not prevent an animal from doing anything in particular, but it makes actions hesitant and clumsy. This precision is not built-in, but learned by trial and error. Learning how to ride a bicycle is an example of a type of neural plasticity that may take place largely within the cerebellum.

The tectum, often called "optic tectum", allows actions to be directed toward points in space. In mammals it is called the "superior colliculus", and its best studied function is to direct eye movements. It also directs reaching movements, though. It gets strong visual inputs, but also inputs from other senses that are useful in directing actions, such as auditory input in owls, input from the thermosensitive pit organs in snakes, etc.

The pallium is a layer of gray matter that lies on the surface of the forebrain. In reptiles and mammals it is called cortex instead. The pallium is involved in multiple functions, including olfaction and spatial memory. In mammals, where it comes to dominate the brain, it subsumes functions from many subcortical areas. The hippocampus, this part of the brain is involved in spatial memory and navigation in fishes, birds, reptiles, and mammals.[35]

The basal ganglia are a group of interconnected structures in the forebrain. The primary function of the basal ganglia seems to be action selection. They send inhibitory signals to all parts of the brain that can generate actions, and in the right circumstances can release the inhibition, so that the action-generating systems are able to execute their actions. Rewards and punishments exert their most important neural effects within the basal ganglia.

The olfactory bulb is a special structure that processes olfactory sensory signals, and sends its output to the olfactory part of the pallium.

HEART:

The heart is a muscular organ in all vertebrates responsible for pumping blood through the blood vessels by repeated, rhythmic contractions. The heart is composed of cardiac muscle, an involuntary striated muscle tissue which is found only within this organ. In

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mammals, the function of the right side of the heart (see right heart) is to collect de-oxygenated blood, in the right atrium, from the body (via superior and inferior vena cavae) and pump it, via the right ventricle, into the lungs (pulmonary circulation) so that carbon dioxide can be dropped off and oxygen picked up (gas exchange). This happens through the passive process of diffusion. The left side (see left heart) collects oxygenated blood from the lungs into the left atrium. From the left atrium the blood moves to the left ventricle which pumps it out to the body (via the aorta). On both sides, the lower ventricles are thicker and stronger than the upper atria. The muscle wall surrounding the left ventricle is thicker than the wall surrounding the right ventricle due to the higher force needed to pump the blood through the systemic circulation.

The heart is effectively a syncytium, a meshwork of cardiac muscle cells interconnected by contiguous cytoplasmic bridges. This relates to electrical stimulation of one cell spreading to neighboring cells. Some cardiac cells are self-excitable, contracting without any signal from the nervous system, even if removed from the heart and placed in culture. Each of these cells has its own intrinsic contraction rhythm. A region of the heart called the sinoatrial node SA node, or pacemaker, sets the rate and timing at which all cardiac muscle cells contract. The SA node generates electrical impulses, much like those produced by nerve cells. Because cardiac muscle cells are electrically coupled by inter-calated disks between adjacent cells, impulses from the SA node spread rapidly through the walls of the artria, causing both artria to contract in unison. The impulses also pass to another region of specialized cardiac muscle tissue, a relay point called the atrioventricular (AV) node, located in the wall between the right artrium and the right ventricle. Here, the impulses are delayed for about 0.1s before spreading to the walls of the ventricle. The delay ensures that the artria empty completely before the ventricles contract. Specialized muscle fibers called Purkinje fibers then conduct the signals to the apex of the heart along and throughout the ventricular walls. The Purkinje fibres form conducting pathways called bundle branches. The impulses generated during the heart cycle produce electrical currents, which are conducted through body fluids to the skin, where they can be detected by electrodes and recorded as an electrocardiogram (ECG).

LUNGS:

The lung or pulmonary system is the essential respiration organ in air-breathing animals. Two lungs are located in the chest on either side of the heart. Their principal function is to transport oxygen from the atmosphere into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere. This exchange of gases is accomplished in the mosaic of specialized cells that form millions of tiny, exceptionally thin-walled air sacs called alveoli. Once air progresses through the mouth

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or nose, it travels through the oropharynx, nasopharynx, the larynx, the trachea, and a progressively subdividing system of bronchi and bronchioles until it finally reaches the alveoli where the gas exchange of carbon dioxide and oxygen takes place. The drawing and expulsion of air (ventilation) is driven by muscular action. In addition to their function in respiration, the lungs also:

alter the pH of blood by facilitating alterations in the partial pressure of carbon dioxide

filter out small blood clots formed in veins

filter out gas micro-bubbles occurring in the venous blood stream such as those created after scuba diving during decompression.[4]

influence the concentration of some biologic substances and drugs used in medicine in blood

convert angiotensin I to angiotensin II by the action of angiotensin-converting enzyme

may serve as a layer of soft, shock-absorbent protection for the heart, which the lungs flank and nearly enclose.

Avian lungs do not have alveoli as mammalian lungs do. They contain millions of tiny passages known as para-bronchi, connected at both ends by the dorsobronchi. The airflow through the avian lung always travels in the same direction - posterior to anterior. This is in contrast to the mammalian system, in which the direction of airflow in the lung is tidal, reversing between inhalation and exhalation. By utilizing a unidirectional flow of air, avian lungs are able to extract a greater concentration of oxygen from inhaled air. Birds are thus equipped to fly at altitudes at which mammals would succumb to hypoxia. This also allows them to sustain a higher metabolic rate than an equivalent weight mammal.

LIVER:

The liver is the largest glandular organ of the body. This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the emulsification of lipids. It also performs and regulates a wide variety of high-volume biochemical reactions requiring highly specialized tissues, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital The liver

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is necessary for survival; there is currently no way to compensate for the absence of liver function. The physiological functions of liver are:

A large part of amino acid synthesis The liver performs several roles in carbohydrate metabolism:

o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol)

o Glycogenolysis (the breakdown of glycogen into glucose)

o Glycogenesis (the formation of glycogen from glucose)

The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation

The liver also performs several roles in lipid metabolism:

o Cholesterol synthesis

o Lipogenesis, the production of triglycerides (fats).

The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and antithrombin.

In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.

The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.

The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.

The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein hormone that regulates the production of platelets by the bone marrow.

The breakdown of insulin and other hormones

The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment (bilirubin and biliverdin).

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The liver breaks down toxic substances and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.

The liver converts ammonia to urea.

The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin A (1–2 years' supply), vitamin D (1–4 months' supply), vitamin B12, iron, and copper.

The liver is responsible for immunological effects- the reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system.

The liver produces albumin, the major osmolar component of blood serum.

The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood pressure when activated by renin, a kidney enzyme that is released when the juxtaglomerular apparatus senses low blood pressure.

KIDNEY:

The kidneys are paired organs, which have the production of urine as their primary function. They are part of the urinary system, but have several secondary functions concerned with homeostatic functions. These include the regulation of electrolytes, acid-base balance, and blood pressure. In producing urine, the kidneys excrete wastes such as urea and ammonium.

summary of physiologic activities in nephrons and collecting ducts during formation of urine

Component of Nephron Physiologic Process Glomerulus Passive formation of ultrafiltrate of plasma devoid of most protein. Bowman's capsule Collection of glomerular filtrate Proximal tubule Active Reabsorption of: Glucose, proteins & amino acids,

vitamins, ascorbic acid,acetoacetate, hydroxybutyrate, uric acid, sodium, potassium, calcium ( by PTH), phosphate ( by PTH), sulfate, bicarbonate Passive Reabsorption of: Chloride, water, urea Active Secretion of: Hydrogen ion

Henle's loop Generation of medullary hyperosmolality Descending limb Passive Reabsorption of: Water

Passive Secretion of: Sodium, urea Thin ascending limb Passive Reabsorption of: Urea, sodium, impermeable to water

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Thick ascending limb Active Reabsorption of: Chloride, calcium Passive Reabsorption of: Sodium, impermeable to water, potassium

Distal tubule Active Reabsorption of: Sodium ( by aldosterone), calcium, HCO3, small amounts of glucose Passive Reabsorption of: Chloride, water ( by ADH) Active Secretion of: Hydrogen ion, ammonia, uric acid Passive Secretion of: Potassium

Collecting ducts Active Reabosorption of: Sodium ( by aldosterone) Passive Reabsorption of: Chloride, water ( by ADH)Active Secretion of: Hydrogen ion Passive Secretion of: Potassium

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THERAPEUTIC PROTOCOLS IN 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), Staphylococcus spp,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. Retrobulbar and orbital tissues are most frequently treated systemically.

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. Topical administration is also affected by the Vehicle, molecular size of the drug, drug concentration, pH, electrolyte composition and preservatives.

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Corneal epithelium is the main site of resistance to drug penetration. The cornea may be thought of as a fat-water-fat sandwich. As a result, the epithelium and endothelium are relatively impermeable to electrolytes but are readily penetrated by fat-soluble substances. The stroma is readily penetrated by electrolytes but not 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. Sub conjunctival (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. Subconjunctival administration is used for diseases of the cornea, anterior, uvea, anterior vitreous, and sclera. Subconjunctival or sub-Tenon’s therapy, while not a true form of systemic medication, has potentially increased drug absorption and contact time. Medications both leak on to the cornea from the entry hole of injection and diffuse through the sclera into the globe. 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:

They 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 and antifungal drugs have been effectively used in microgram dosages. Generally injected at the pars plana for infectious endophthalmitis.

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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.

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 application frequency of topical antimicrobials depends on the disease and drug formulation. one drop of an antimicrobial solution applied four times daily is usually sufficient in the treatment of 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 incompatibility. 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.

1. 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

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against gram negative bacteria and pseudomonas spp. Frequency of administration- q4 hrs for full therapeutic levels. Toxicity- risk of aplastic anemia.

2. 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 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.

3. 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.

The combination of neomycin,bacitracin and polymixin B is known as “triple antibiotic” which is first choice antimicrobial for bacterial conjuctivits,corneal ulcers and prophylaxis against surface infection.

4. 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

5. Fluoroquinolones: Eg: Ciprofloxacin HCl ,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

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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:

Antiviral agents are indicated for treatment of herpetic keratitis in cats. Corticosteriods should never be used in the suspected ocular eye infections as they further aggravate the condition. The topical antiviral agents are static in action and topically irritating, so frequent administration is necessary and client compliance and patient tolerance are issues.

1. Idoxuridine: 0.5% ointment and 0.1% solution. Frequency of administration is 1 drop every 4hrs until corneal re-epithelialization occurs. Does not 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.

2. 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 hrs for 7 days. Acts by Preventing extension of the DNA chain by causing a premature stop to DNA replication

3.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. Like idoxuridine, trifluridine inhibits nucleic acid synthesis,penetrates the intact cornea, ulceration and uveitis increase its intraocular penetration.it is administered 4-9 times daily for 2 days, and then the frequency is reduced over the next 2-3 weeks.

4. Others: Lysine, Acyclovir, Interferons

Antifungal ocular drug therapy :

Ocular antifungal agents belong to one of three classifications: polyenes, imidazoles, and pyrimidines.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.

1. Polyenes :

a. Natamycin : Used mainly against Candida spp. and Fusarium spp. (only approved agent in the market)

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b. Amphotericin B: Fungistatic, generally used systemically for fungal endophthalmitis, may be given as an intravitreal injection in mcg dosages.

2. Imidazoles

a. Miconazole 1%: Drug of choice for most veterinary fungal keratitis cases, but no longer readily available in IV preparation. 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.

b.Fluconazole: Synthetic triazole, fungistatic. Strength 2 mg/ml IV preparation. Currently drug of choice for topical use, subpalpebral lavage unit, and intracameral (100 μg) injection. Treatment frequency for fungal keratitis may warrant 2 to 4hr treatment intervals.

Anti-inflammatory ocular drug therapy:

1. 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..

2. Nonsteroidal anti-inflammatory ocular drugs : They include salicylic acids (aspirin),Propionic acids , Indomethacin ,Phenylbutazone, Flunixin meglumine etc . 1. Aspirin: Most effective when used prior to prostaglandin release. Dosages: Dog-10 to 20 mg/kg, BID; Cat-10 mg/kg, q 48 hrs.

2. Carprofen : Used in similar ways as aspirin. May have fewer side effects. Do not use in Labrador retrievers - may cause liver disease. Dosages: 2.2mg/kg BID. Not approved for use in cats.

3. Etodolac : Dosage: Dog-10 - 15 mg/kg, PO SID. Should not be used in Dogs < 5 kg

Monitor tear production-associated with development of KCS

4. Flunixin meglumine: Effective anti-inflammatory agent in the Horse and Dog ,

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although not currently approved for use in Dogs. Dosages: 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 (i.e., lens extraction).; Not to be used. In cat.

5. Flurbiprofen: Used topically preoperatively to stabilize the blood-aqueous barrier in inflammation (in diabetes mellitus), decrease production of ocular prostaglandins and maintain pupil size. Can be used to treat anterior uveitis and in the presence of corneal ulceration.

Ocular topical Anesthetics:

Drugs suitable for use as local anesthetics cause a reversible block of conduction through nerve fibers by displacing calcium at binding sites in cell membranes. 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. Increased membrane permeability exists in an alkaline state. 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 they 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 : 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: Prescribed as 2 drops of 2% Pilocarpine per 4.5kg body weight added to the food twice daily. Maintain therapy for at least 1 month prior to recheck.Side effect-emesis or anorexia-if this occurs-stop therapy for 24 hrs and start again at one half the dose, gradually increasing to the starting dose.

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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.

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.

1. Acetylcysteine : Anticollagenase (i.e,. Pseudomonas aeruginosa infection). Diluted 10 to 20% with artificial tears to a 5 to 8% concentration. Administered every 1 to 4 hrs until desired effect is achieved. Overuse may result in localized inflammation and excessive lysis of normal mucus, thus worsening corneal exposure.

2. Autogenous serum – anticollagenase: Use topically. Must be refrigerated and each batch used for only 7 days - it is an excellent growth media for microorganisms.

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CARDIO VASCULAR EMERGENCIES: INTERPRETATION AND CLINICAL MANAGEMENT

SANTOSH . P. SARANGAMATH

Cardiology is an interesting subject in recent times not only in human medicine but in veterinary sciences as well. Recent diagnostic techniques and therapy have not only improved the expectency of the life but also increased quality of life in dogs. Overall the incidence of heart diseases in dogs is estimated to be 10 to 14 % and majority of the geriatric patients (aged dogs) tend to suffer from valvular diseases. Physical examination cardiac ailments requires great expertise, if history and signs are included in the physical examination then probably more than 80 % of case diagnosis can be made effectively.

Signalment:

Age: congenital heart diseases = < 2 years, cardiomyopathies + 2 to 7 years, Valvular insufficiency=7 to 9 years. Breed: Patent ductus arteriosis= Pomaranian, coolie, poodle. Aortic arch abnormilities = GSD, Grate dane. Mitral/trricuspid valvular insuffiency= Daschund, Pomaranian, Poodle, Cocker spanial. Dialted cardiomyopahty= Doberman, large breeds of dogs.

History: most patients with cardiac diseases have exercise intolerance at some level of excertion. In most instances cardiac diseases begins somewhat insidiously with slow progression over a period of several months to years. With right sided failure, ascites, hepatomagaly occur initially where as with left sided failure coughing, pulmonary odema and dyspnoea are commonly observed. History of fainting, syncope or collapse can also be observed in dogs with arrythmias. Functional ability of the other organs too get affected like kidney and liver.

Physical examination: most of the dogs look apparently normal, but they progressively go down in condition and may look thin to cachetic in later stages. Affected animals stand with abducted elbows indicating respiratory distress or pulmonary oedema. Cyanosis of the visible mucous membrane may result from right to left shunting of blood as in case of tetralogy of fallot, atrial septal defect and ventricular septal defect. Increased capillary refill time may be noticed in conditions of shock, mitral valve insufficiency. Superficial veins, jugular vein distension can be observed in right sided failure or pericardial effusion.

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Pulse: normal rate is 70-160 beats/min. Arrhythmia is characterized by irregular pulse rate that is corellated with respiration. Pulse defecit is seen when there are more heart beats than the femoral pulses. Greater the pulse deficit indicate more severe problem of arrhythmia.

Ascultation: most important in assessing heart diseases. Both heart and lungs should be asculted. 4 sounds are produced normally, but first 2 are heard frequently in dogs.

Murmers: are abnormal heart sounds as a result of vibration produced by the flow of blood (turbulence in blood flow) in the heart or greater vessels.

Laboratory examination:

Combined with the history, physical examination, ECG tracings, Radiographs, Ultrasonography, Phonocardiography and Angiography can usually pin down the diagnosis of heart defect. The later diagnostics are special techniques which provide the most exact view of the heart and great vessels,and can help clinicians to confirm a diagnosis or evaluate the severity of the heart defect.

While performing clinical examination, observations such as pulse character, mucous membrane color, capillary refill time, heart sounds are most important part of initial work up. Detection of heart murmur during auscultation, coughing, dyspnoea, ascites are some of the things which make clinicians to suspect cardiac involvement. Some of the different conditions that can be diagnosed with the help of ECG in dogs are:

Evaluation of cardiac chamber enlargement Evaluation of Arrhythmias Evaluation of therapy- drug therapy e.g. Digitalis/ Propranolol/Quinidine etc

Interpretation of ECG:The systemic Electrocardiographic interpretation can be done by monitoring Heart rate Heart rhythm Measurement of complexes and intervals Mean electrical axis of the heart

COMMON ECG ABNORMALITIES:

A. HYPERTROPHY OF THE CARDIC CHAMBERS: i) Right atrial hypertrophy : Tall “ P” wave, usually ≥ 0.4 mv on lead IIii) Left atrial hypertrophy : wide “ P “ wave, usually ≥ 0.05 sec on lead IIiii) Right ventricular hypertrophy: Deep “ S” wave usually ≥ 0.35 mv

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iv) Left ventricular hypertrophy : wide “ QRS” complexes usually ≥ 0.06 sec along with height of the “R” wave is ≥ 2.5 mv in laed II

v) Biventricular Hypertrophy: Tall “ R” wave, wide “ QRS” complexes and deep “S” wave in lead II

B. CONDUCTION ABNORMALITIES:i)_Atrio-venticular heart block : occurs due to delay in transmission of impulses from AVN to bundle of Hisa) Ist degree AV Block: “PR” interval ≥ 0.13 sec.b) II nd degree heart block: some “P” waves without “QRS” complex.c) IIIrd degree heart block: more of “P” waves without ‘QRS” complex.

ii) Bundle Branch Block(BBB) : occurs due to interruptions in the transmission of impulses through left and right bundle of Hisa) Right BBB: wide “S” wave, QRS duration ≥ 0.08 secb) Left BBB : QRS duration ≥ 0.08 sec, but may be seen in left ventricular

hypertrophy, so, thoracic X-ray is must to differentiate this hypertrophy

C. EFFECT OF ELECROLYTE DISTURBANCES ON ECG a) Hypokalaemia : Tal “T”ve, “P” wave flattened. b) Hyperkalaemia: Prolonged “Q-T” interval and small biphasic “T” wave (+ ve or – ve deflection) c) Hypocalcaemia and Hypercalcaemia : prolonged “Q-T” interval and “ST” segment elevation

D. ECTOPIC ARRYTHMIASa) Atrial fibrillation: most common arrhythmias seen in small animal, depolarization occurs randomly throughout atria, here “P’ waves are replaced by “F” waves (saw toothed waves) i.e. fine irregular movement of the base line observed as a result of atrial fibrillation.

b) Ventricular fibrillation: it is a terminal event associated with cardiac arrest, depolarization occurs randomly throughout ventricles, here large fine, irregular, bizarre movement of base line without waves or complexes are observed.

ECG and radiography are the basic needs of the cardiac evaluation; the results of these along with history and physical examination make clinician to arrive at a definitive diagnosis. Although ECG is quite useful, it is not HIGHLY sensitive for detecting hypertrophy of the heart chambers; it only supports a differential diagnosis and should not be considered a definitive diagnostic test.

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CONGENITAL DEFECTS :

Subvalvular aortic stenosis : left ventricular out flow is obstructed below the arotic valve and include incomplete fibrous ridges, discrete fibrous rings, such dogs usually won’t bred, balloon catheter dilatation( like balloon angioplasty in humans) of the sub aortic area is found to be helpful.

Pulmonic stenosis : right ventricular out flow obstructed along with pulmonic valve dysplasia characterized by thickening of valves, various surgical procedures are employed to correct this apart from the balloon catheter dilatation.

Patent ductus arteriosus : where in pulmonary artery gets fused with aorta, leading to increased flow of blood from the aorta to pulmonary artery leading to increased pulmonary flow, intern increased pulmonary venous return to ventricles resulting in volume overload in ventricles ending up with left side congestive heart failure, surgical ligation is the best method for clinical management though such animals are not used for breeding purpose.DILATED CARDIOMYOPATHY AND HYPERTROPIC CARDIOMYOPATHY

Most common disease in dogs and cats, initially anorexia, weakness, exercise intolerence, coughing, pulmonary odema, syncope with progression to congestive heart failure. Treatment should be directed towards (1) reducing the elevated ventricular pressure in order to relieve congestion- i.e. oedema (2) increasing forward stroke volume and (3) Optimizing heart rate and rhythm

Regardless of the underlying cause, decrease in filling pressure with alleviating oedema is achived by administration of diuretics. Such animals should receive furosemide parentrally at the rate of 2 – 3 mg/kg until it stabilizes.Refractory oedema cases are most effectively controlled by adding a second diuretic that acts at different site at kidney, i.e. spiranolactone at the dose rate of 1-2 mg/kg BID (PO)  or thiazide diuretic (hydrochlorothiazide) at the dose rate of 2-4 mg/kg BID (PO). List of diuretics used in case of cardia ailmentsBendroflumethiazide Dog 0.2-0.4 mg/kg BID (PO) Hypovolemia, as for

hydrochlorthiazide Cat undetermined  Bumetanide   Dog 0.01-0.5 mg/kg total (IV);

0.03-0.06 mg/kg SID-BID (PO)  Hypovolemia, hypokalemia, metabolic alkalosis  

Cat unknown  Chlorthiazide   Dog 20-40 mg/kg BID-TID (PO)   Hypovolemia, hypokalemia,

metabolic acidosis  Cat 20-40 mg/kg BID (PO)  Furosemide   Dog 2-4 mg/kg BID-TID (IV, IM, SQ,

PO); 2-8 mg/kg q 1h (IV) in severe pulmonary edema  

Hypovolemia, hypokalemia, metabolic alkalosis, deafness

Cat 1-2 mg/kg BID-TID (PO, IM, IV), do not exceed 2 mg/kg (IV)  

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Hydrochlorothiazide   Dog 2-4 mg/kg BID (PO)   Hypovolemia, hypokalemia, metabolic acidosis, GI, hyperglycemia  

Cat 1-2 mg/kg BID (PO)  

Spironolactone   Dog 1-2 mg/kg BID (PO)   Hypovolemia, hyperkalemia, GI  Cat 1-2 mg/kg BID (PO)  

Triamterene   Dog 1-2 mg/kg daily (PO)   Hypovolemia, hyperkalemia, metabolic acidosis  Cat unknown  

The only universally applicable recommendation for increasing cardiac output is to optimize heart rate and rhythm. Arteriolar dilators and positive ionotropic agents are used to achive this, such as potent ionotropes like dobutamine ( 5 – 10µ/kg i.v) and dopamine or amrinone ( 1-3mg/kg initially). Positive inotropic therapy functions to enhance contractility. These agents have been thought to be indicated when contractility is reduced (systolic dysfunction).

Once the patient condition stabilizes then digoxin is administered at 0.007 mg/kg orally once in 2 days. Vasodilators such as enapril ( 0.25-0.5 mg/kg orally b.i.d) are administered. Digoxin has 3 benefiial effects such as it decreases sympathetic response, increasing the myocardial contractility by inhibiting K-Na ATPase and it slows the impulse conduction through AV node there by decreases the arrhythmias.

Other positive ionotropic drugs used include bipiridine compound class of drugs. (amrinone and milrinone). Phemobendan, a benzimidazole compound, is also a phosphodiesterase inhibitor which also has calcium sensitizing effect. Thus, this drug increases the sensitivity of the cardiac myofibrils to the calcium, there by improving the strength of contraction of the myocardium. Doasge of Pimobendan: Dog: 0.25/kg BID on an empty stomach.Therapy for common Cardiac Arrhythmias :

The best therapy for most of the arrhythmia is to eliminate the underlying causes which may be of intrinsic cardiac disease (like myocardial diseases, infiltrative diseases, Ischemia, Hypertension, congenital heart disease, conduction disorders etc,), Hypoxia( systemic- anemia, anaesthesia, local-myocardial infarction), Metabolic diseases (like Acid-Base disorders, Neurologic disease, Endocrine disorder), Infection ( sepsis, Pyrexia). Some of these can be ruled out by history, physical examination, blood examination and other routine diagnostic tests. Most clinicians agree that the presence of clinical signs (weakness, Syncope) in conjunction with an arrhythmia warrants anti-arrhythmic therapy.

Some of the antiarrhythmic drugs used in dogs and cats are:

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Amiodarone   Dog 10-20 mg/kg SID (PO) for 7-10 days (loading dose), then 3-15 mg/kg SID

Pulmonary fibrosis, GI, hepatitis, leukopenias, bradycardia  Cat Unknown  

Aprindine   Dog 0.5-2.0 mg/kg (IV); TID (PO)   GI, seizure, hepatitis  Cat Unknown  

Digoxin   Dog 0.22 mg/m2 BID (PO)   GI, depression, anorexia, bradycardia, arrhythmias  Cat 1/4 of 0.125 mg (PO) q 48h - SID  

Flecainide   Dog 1-5 mg/kg BID-TID (PO); Dr. Fox suggests 3-10 mg/kg TID (PO) 1-2 mg/kg (IV) slowly  

GI, weakness, confusion, depression  

Cat Unknown  Lidocaine   Dog 2-4 mg/kg slow (IV), repeat q 10

min. to maximum of 8 mg/kg; 25-75 ug/kg/min (CRI)  

Seizures, CNS excitation (seizures), GI, arrhythmias, hypotension  

Cat 0.25-1.0 mg/kg slow (IV) over 5 minutes  

Mexiletine   Dog 2-5 mg/kg BID-TID (PO) (oral lidocaine) Dr. Fox suggests 5-10 mg/kg BID-TID (PO)  

As for lidocaine  

Cat unknown  Phenytoin   Dog 5-10 mg/kg (IV) slow; 35 mg/kg

TID (PO)  Depression, seizures  

Cat None  Procainamide   Dog 6-8 mg/kg (IV) over 5 min; 25-40

ug/kg/min (CRI); 8-20 mg/kg q 4-6 hr (IM), TID (PO) (slow release formulation)  

Weakness, hypotension, negative inotropic, GI, bradycardia  

Cat 8-20 mg/kg TID (PO)  Propafenone   Dog 3-6 mg/kg q8 hrs   Transient arrhythmia &

hypotension  Cat unknown  Quinidine   Dog gluconate 6-20 mg/kg QID (IM);

Extentab (sulfate) 6-16 mg/kg TID (PO); Quinaglute, Cardioquin 8-20 mg/kg TID-QID (PO); 5-10 mg/kg (IV)  

As per procainamide, interacts with digoxin  

Cat Sulfate 5.5-11.0 mg/kg TID (PO)  Sotalol   Dog 0.5-2 mg/kg BID (PO)   As per beta-blockers  

Cat Unknown  Tocainide   Dog 5-10 mg/kg TID-QID (PO); (oral

lidocaine) Dr. Hamlin suggests 25 mg/kg QID (PO)  

As for lidocaine  

Cat unknown  

Beta blockers / calcium chnanel blockers:In dogs, Digitalis glycosides are useful in slow downing HR associated with

sinus tachycardia, atrial fibrillation, or supraventricular arrhythmias. If does not controlled with this, a beta blocker or a calcium channel blocker is added to the

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therapeutic regimen. The use of beta-blockers therefore can counteract the excess catecholamines typical of heart failure, actually resulting in improved systolic function in the long term and increased survival time. Beta-blockers increase survival in people with heart failure. They can protect against arrhythmic death (sudden death). Dosage of certain beta blockers ( Propranolol, metopralol, Atenolol) are given below in dogs and cats. Calcium channel blockers, including diltiazem also used as adjunct to digoxin therapy for heart rate control. Propranolol : dog: 0.2-1.0 mg/kg TID (PO); 0.02-0.06 mg/kg (IV) slowly , cat: 0.2-1.0 mg/kg BID-TID (PO); 0.04 mg/kg (IV) slowly.Metoprolol: dog: 0.25-1 mg/kg BID-TID (PO), cat: 0.25-1 mg/kg BID-TID (PO) Atenolol : dog: 5-12.5 mg SID-BID (PO) or 0.25-1 mg/kg SID-BID (PO) , cat: 5-12.5 mg SID-BID (PO) Carvedilol : Dog: up to 0.5mg/kg BID (PO), Cat: unknownACE Inhibitors : ACE inhibitors have been shown to improve the length of survival of dogs with CHF secondary to Dilated Cardiomyopathy. Enapril is found to be beneficial in the treatment of CHF. ACE inhibitors block production of angiotensin II (potent arterial constrictor) and block production of aldosterone (which contributes to fluid overload), thereby causing vasodilation and reduction of fluid retention. Through both of these actions ACE inhibitors appear to delay the progression of heart failure. In dogs with chronic mitral valve insufficiency (CMVI), ACE inhibitors reduced mortality.Dosage; Enalapril in case of dog: 0.5 mg/kg SID-BID (PO), usually BID and in cases of cats 0.5 mg/kg SID (PO), Benazapril in case of dogs is 0.5 mg/kg SID-BID(PO), usually BID and in cats the dosage is 0.25-0.5 mg/kg SID (PO). Nitrates : Nitropruside a potent vasodilator, its effectiveness in veterinary medicine is not been clearly proven. However, transdermal placement of nitroglycerine is used in combination with digoxin, lasix to stabilize the heart failure patient.

VALVULAR DEGENERATION ( ENDOCARDITIS) :

This is common in certain breeds like GSD, bull terrier, Grate Dane. Seen most commonly in older dogs and dogs over 13 years will exibit murmurs upon ascultation.Diagnosis requires echocardiography. Surgical intervention, including valve reconstruction, valve replacement and annuloplasty of the mitral valve has been successful in associated clinical signs.

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CLINICAL MANAGEMENT OF RESPIRATORY DISORDERS

SANDEEP HALMANDGE

Diseases of respiratory tract are commonly encountered in routine clinical practice and there fore form important clinical entity for the clinicians. The causes of respiratory disorders are multiple and complex, but the factors of stress, viral infection and bacterial infection are almost always involved in cases of severe disease. A wide variety of different stressors and agents may be involved in the disease process.

Stress factors Viral agents Bacterial agentsHeatColdDustDampnessInjuryFatigueDehydrationHungerAnxietyIrritant gasesNutritional deficienciesSurgery

PI 3IBRBVDBRSVAdenovirusRhinovirusHerpesvirusMCF

PasteurellaHaemophilusKlebsiellaMycobacteriumMycoplasmaStreptococcusOthers

Principal manifestations of respiratory insufficiency:

The functional integrity of respiratory system depends on its ability to exchange oxygen in place of carbon dioxide from the venous circulation. Therefore, failure of adequate oxygenation of tissues is a sign of respiratory insufficiency and is termed as HYPOXIA.

Clinical hypoxia can be of four types viz;

a) Reduced oxygen carrying capacity of the blood (Anaemic hypoxia) seen in nitrite

poisoning and carbon monoxide poisoning,

b) Insufficient alveolar ventilation (Anoxic hypoxia) seen in strangulation, lung disease

c) Reduced blood flow (Stagnant hypoxia) seen in congestive heart failure and

D) Inability of tissues to utilize oxygen (Histotoxic hypoxia) encountered in cyanide

poisoning.

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Nasal discharge: Serous, mucoid, muco-purulent nasal discharge is usual indication of respiratory tract disease. Mucoid and serous discharge indicate acute inflammatory disease whereas, muco-purulent always suggest secondary bacterial invasion. Close inspection of nasal cavity helps in determining the origin of nasal discharge. Unilateral discharge suggests a local problem whereas, bilateral indicates systemic involvement.

Bleeding from the nose is referred as epistaxis and if it is profused rhinnorhagia, Whereas, haemaptysis is coughing up of blood usually from lower respiratory tract.

Polypnea is rapid breathing, Tachypnea is very rapid and shallow breathing and Hyperapnea is an abnormal increase in rate and depth of breathing but not up to the point of labored. Dyspnea is difficult or labored breathing and can be of two types:

Expiratory dyspnea is prolonged and forceful expiration associated with chronic obstructive lower airway diseases (COPD).

Inspiratory dysnea is prolonged and forceful inspiratory effort associated with obstruction of upper respiratory airway (Laryngeal paralysis, obstruction, collapse of tracheal rings).

Abnormal respiratory sounds:

Crackles are popping/bubbling sounds originating from lungs and suggestive of presence of oedematous exudate in alveoli and bronchi. Wheezes are continuous squeaking/whistling sound caused by passing of air through narrowed airway. These are suggestive of presence of tenacious exudate or narrowing of airways.

Pleuritic frictional sounds are produced due to rubbing of inflamed parietal and visceral pleural surface against each other which are more pronounced during expiration and are suggestive of pleurisy or diffused pulmonary emphysema. Absence of lung sounds or silent lung is suggestive of space occupying lesion in the thoracic cavity or consolidation of lungs.

Coughing :

It is an explosive expiration of air from lungs which is initiated by stimulation of cough centre located in medulla oblongata due to irritation of sensory receptors of airways. Productive cough is suggestive of presence of exudative lesion and there is expulsion of mucus and inflammatory debris, whereas, non-productive cough indicate inflammation with minimal exudation.

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Cyanosis (Bluish discoloration) of visible mucosae is indicative of serious respiratory insufficiency. Common causes of cyanosis include congenital heart diseases and all types of hypoxias.

DIAGNOSTIC APPROACH TO RESPIRATORY TRACT DISORDERS:

Clinical examination of the patient:

Clinical examination of patient suspected for respiratory disorder will definitely carry a history of poor working performance, early exhaustion, abnormal breath sounds and presence of one or the other clinical evidence like nasal discharge, respiratory distress at rest, coughing. A thorough physical and clinical evaluation of the patient will help the clinician to pinpoint the ongoing illness of which auscultation is the most important indispensable tool.

Special techniques :

Nasopharyngeal swab, percutaneous trans-tracheal aspiration, broncho-alveolar lavage are used as special diagnostic techniques in the diagnosis of respiratory tract dysfunction. Elevated absolute neutrophil count in broncho-alveolar lavage fluid (BALF) is considered as diagnostic feature of COPD in horses. Similarly, presence of haemo-siderophages in the BALF in thoroughbred horses is suggestive of pulmonary haemorrhage.

Use of fiber-optic endoscope has improved the diagnostic skill of the physician and is routinely being used in canine and equine practice. Flexible fiber-optic endoscope has clinical advantage of non-invasiveness, visual inspection of airways and collection of sample with minimal contamination.

Thoracic radiography is a valuable diagnostic tool for diseases of lungs and helps in detecting atelectasis, consolidation of lung parenchyma, space occupying lesion and pleural effusions. Ultrasonography has a limited use but can be used for guided thoracocentesis.

Pulmonary function tests :

Capnography means measurement of carbon di-oxide content of breath. Measurement of respiratory volume, residual air and vital capacity of lung is referred as Spirography.

PRINCIPLES OF TREATMENT OF RESPIRATORY TRACT DISORDERS:

1. Selection of antibiotic:A course of antibiotic is essential to counteract the bacterial invasion. The choice of antibiotic depends on cost effective ratio, sensitivity of

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microorganisms and effective penetration of the drug. Parenteral use of any one of the following can be of choice under field conditions.

Combination of Sulpha-trimethoprim @ 20 mg/kg body weight. Ampicillin, Amoxycillin or Amoxicillin and Cloxacillin combination @ 10 mg/kg

b.wt. Third generation cephalosporins like Ceftazidime, Ceftrioxone @ 10 – 20 mg/kg

b.wt. Recently extended spectrum Cephalosporins are gaining importance in large animal

practice. Tazobactam is a new beta lactamase inhibitor and its combination with Cetrioxone has been reported very effective in complicated respiratory tract infections with gram positive, gram negative as well as few anaerobes belonging to Clostridial group.

Amikacin, Azithromicin have promosing role in small animal practice.2. Environmental alterations: Provision of comfortable, well ventilated environment

during convalescence brings about early recovery.

3. Use of antihistamines is beneficial to antagonize the deleterious effects of histamine and other substances.

4. Respiratory stimulants like CO2, nikethamide, leptazole, caffeine and amphetamine are widely used. doxapram hydrochloride, a centrally acting respiratory stimulant is commonly used to antagonize respiratory depression in equine practice.

5. Mucokinetic drugs and broncodialators have effective mucocilliary clearance and better penetration of antibiotic in the treatment of respiratory diseases. Bromohexine, theophylline are drugs of choice. β–adrenergic agonist bronchodialator e.g. clenbuterol is used in the treatment of chronic obstructive pulmonary disease.

6. Expectorants are indicated to expel the mucus from the respiratory tract. Sedative expectorants containing ammonium chloride are used in exhaustive, tenacious cough whereas; codeine or dextramethorphan containing expectorants are indicated in non-productive cough to suppress the cough center.

DISEASES OF LUNG:

Pulmonary congestion and oedema:

Engorgement of pulmonary vascular bed and subsequent increase in the amount of blood in lung parenchyma is called as pulmonary congestion which later on leads to escape of fluid into interstitial space and alveoli referred as pulmonary oedema.

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Etiology: Primary pulmonary congestion is due to inhalation of toxic fumes and smoke, anaphylactic shock, hypostatic congestion of lungs (prolonged recumbency due to downer cow syndrome, milk fever, fracture of long bone). Secondary congestion occurs due to congestive heart failure.

Pulmonary oedema can occur due to acute anaphylaxis, pneumonic pasteurellosis, gram negative sepsis in pigs, CHF, inhalation of toxic gases and fumes, pulmonary form of African horse sickness and Barker syndrome in foals.

Pathogenesis: Reduced effective alveolar space, reduced vital capacity of lungs and impaired oxygenation of blood are the hallmarks of pulmonary congestion and oedema. The end effect is anoxic hypoxia.

Clinical signs: Increased depth of respiration to the point of extreme dyspnea, open mouth breathing, typical stance with front legs spread wide apart and abducted elbows. Presence of crackles (moist rales) on auscultation over lower parts of lungs is characteristic.

Diagnosis:

Clinical findings.

Laboratory investigation like bacterial isolation from nasal swabs, eosinophilia on haematological examination.

Treatment:

Epinephrine in anaphylactic shock.

Antihistamines like pheniramine maleate, promethazine.

Diuretics like furosomide @ 1-2 mg/kg body weight im.

Acetylsalicylic acid is more effective than antihistamines in providing symptomatic relief

Corticosteroids like Hydrocortisone @ 1 mg/kg body weight have beneficial effect as anti-inflammatory agents.

Pulmonary emphysema:

It is distension of lungs caused by overdistension of alveoli with rupture of alveolar wall with or without escape of air into interstitial space.

Etiology: Chronic obstructive pulmonary disease (COPD) in horses is the most important cause of pulmonary emphysema. Moldy hay is linked with COPD in horses. In cattle, acute interstitial pneumonia, lung worm infestation (Dyctiocaulus viviparous), Traumatic pneumonitis due to foreign body and poisonous plants like Senecio quadridentatus, Perilla frutesens are attributing factors for pulmonary emphysema.

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Pathogenesis: Excessive dilatation of alveoli due to narrowing of airways leads to its rupture and escape of air in to interstitial space is the most accepted hypothesis of pulmonary emphysema. Other possible reason could be inherent weakness of alveolar wall and supporting tissue unable to sustain the stress during forceful coughing or exertion. Incomplete evacuation and imperfect oxygenation of blood are the net results of pulmonary emphysema leading to hypoxia.

Clinical findings: Increased rate of respiration at rest is initial sign of pulmonary emphysema. As the disease advances, expiratory dyspnea is evident which gets pronounced during exercise. It is accompanied by expiratory grunt. On auscultation presence of Paper crackling rales over lung parenchyma is sure indication of pulmonary emphysema. Subcutaneous emphysema of wither is considered as sequalae of pulmonary emphysema.

Diagnosis:

Based on clinical findings and evidence of paper crackling rales on auscultation. Narrowing of bronchioles and presence of abundant exudate in airways during

endoscopic examination. High absolute neutrophil count in BALF.Treatment: Reduction of inflammation of airways with NSAID, β-adrenergic bronchodialators like clenbuterol @ 0.8 - 3.2 µg/kg bodyweight and Steroids are indicated. But the prognosis is always guarded.Inhalant corticosteroids in the form of intra-nasal spray have been found effective in controlling the signs of respiratory distress. Sodium cromoglycate is also useful in the treatment of COPD in horses as it prevents degranulation of mast cells.

Pneumonia:

Inflammation of lung parenchyma, accompanied with inflammation of bronchioles and may get complicated with extension of infection to pleura leading to pleuritis.

Etiology:

Pneumonic pasteurellosis (Pasteurella hemolytica) Haemophilus somnus, Klebsiella pneumoniae, Mycobacterium tuberculosis var

bovis, Mycoplasma mycoides var bovis, Fusobacterium necrophorus. Other microorganisms include Actinomyces pyogenus, Streptococcus sp., and Bedsonia sp.

Viral agents like rhinovirus, bovine herpes virus, bovine respiratory syncytial virus, parainfluenza-3, adenovrus-1, 2 and 3.

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Chlamidia and Aspergillus fumigatus like fungal agents. Lungworms (Dictyocaulus viviparous)Pathophysiology: all types of pneumonia is based on interference with gaseous exchange between alveolar air and blood which results in anoxia and hyperapnea. This is manifested clinically by Polypnea, dyspnea or Tachypnea. Later on consolidation of lungs brings about change in quality of breath sounds. Depending on type of exudate, there is evidence of crackles or wheezes on auscultation. Toxaemia in bacterial pneumonia can be life threatening clinical emergency.

Clinical Findings: Rapid shallow breathing is initial cardinal sign of pneumonia which changes to dyspnea in later stages loss of lung parenchyma functionas. Presence of moist, soft but painful cough is suggestive of bacterial broncho-pneumonia. Whereas dry, hacking and paroxysmal cough is indicative of viral etiology. Bilateral muco-purulant nasal discharge, fever, rough hair coat, gaunt appearance, presence of crackles or wheezes on auscultation are observed.

Diagnosis:

Isolation and identification of causative agent from nasal swab, transtracheal aspirate or BALF.

Haematological investigation: Leucopenia is suggestive of viral involvement whereas, leucocytosis is indicative of bacterial invasion. Prominent eosinophilia (>20%) is suggestive of parasitic etiology.

Detection of lung worm larvae in faecal sediment suggests verminous pneumonia Serological tests for confirmation of viral interstitial pneumonia Medical imaging techniques: Thoracic radiography is helpful in detecting radio-

opaque patches suggestive of consolidation of lungs. Ultrasonography also has been proved useful diagnostic aid in detecting pulmonary abscessation and anaerobic bacterial pleuro-pneumonia.

Treatment:

Higher Antibiotics

Antihistamines

Potent anti-inflammatory agents or steroids

Bronchodilators and other supportive therapy.

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CURRENT THERAPEUTIC PROTOCOLS IN HEPATIC DISORDERS

M. VIJAY KUMAR

Liver disorder should always be considered when nonspecific clinical signs, such as depression, weight loss, intermittent fever, and recurrent colic, are present without an apparent cause. Differentiation between acute and chronic hepatitis or failure based on the duration of clinical signs before presentation may be misleading because the disease process is often advanced before clinical signs are evident.Liver biopsy to determine the type of pathology, degree of hepatic fibrosis present, and the regenerative capabilities of the liver parenchyma is necessary for developing a treatment plan and giving an accurate prognosis. Chronic hepatitis patients sometimes need to use antibiotics for unrelated infections and various other procedures and many are not sure about the possible harmful effects some antibiotics may cause their liver.

The 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. The effect is difficult to predict and almost impossible to quantify. There are no tests for hepatic function that will reliably predict drug clearance. Changes in hepatic function due to disease that may affect drug clearance are described by: :i) decreased intrinsic clearance caused by loss of functional hepatic mass ii) Increased fraction unbound of protein-bound drugs. Decreased drug protein binding caused by decreased albumin; this may increase clearance of drugs that are highly protein bound iii) decreased hepatic blood flow resulting in decreased 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. 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.

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PRINCIPLES OF TREATMENT OF LIVER DISEASE

Objectives

Eliminate causative agent Suppress mechanism that potentiate the disease Provide optimum conditions for hepatic regeneration Control manifestations of complication that occur

Specific therapies

Drug-induced –recognition and withdrawal of the drug Bacterial hepatitis/cholangitis –antibiotics Idiopathic chronic hepatitis, lymphocytic cholangitis- steroids , azathioprine Hepatic fibrosis – steroids, colchicines Cholestasis- ursodeoxycholic acid (UCDA) Copper toxicity – decoppering agents Hepatic lipidosis – identify and treat pre-existing disease

Drugs

Antibiotics

Penicillin, ampicillin, cephalosporins, clindamycin, enrofloxacin

Tetracyclines are concentrated in the liver and the bile but are only bacteriostatics

Avoid drugs requiring hepatic metabolism ( or given reduced given dose)

Eg. Chloramphenicol, lincomycin

The following is a list of the most common antibiotics groups being used today. Each 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.

1.Tetracyclines: When used in larger doses, these can cause jaundice, fever, and fatty liver. Metabolism by liver. All tetracyclines are concentrated in liver and excreted via bile into intestine, where they are reabsorbed.

Tetracyclines have adverse effects on several hepatic enzymes, thus to be avoided completely in liver disease

2.Macrolides :

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A.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%. Metabolism by liver,major excretory pathway and it is excreted into bile in active form. Avoid estolate form in liver disease and other forms in usual dosage.

Oleandomycin and triacetyl oleandomycin: Metabolism by liver. No liver toxicity.

B.Lincosamides:

Lincomycin: Metabolism by liver. It is excreted and re-excreted via enterohepatic circulation. Half-life of drug is doubled in liver disease accordingly drug dose should be reduced, or drug avoided entirely.

Novobiocin: Metabolism by liver. Best to avoid in liver disease. This drug may induce "jaundice" by five different methods, all generally uncommon.

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, patients on gut sterilization with kanamycin should be watched for deafness and increasing nephropathy.

Neomycin: Not metabolised by liver. Not more than 6 Gm PO in liver disease for gut sterilization. If azotemia also present,kanamycin is preferred.

Polymyxin- Colistin Group and Vancomycin: Minor metabolism by liver. No change in dose in liver disease.

Chloramphenicol:

Metabolism by liver. 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.

Penicillins: These antibiotics cause the least liver damage. 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. 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

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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. Appreciable Liver tissue levels. Bile levels up to 10-20mcg/ ml on high doses. No change in dose in liver disease.

Cephalosporins: Cephalothin: Metabolism by liver, 70-80% usually excreted unchanged in urine. Advisable to decrease in presence of combined renal-hepatic disease.

Cephaloridine: Metabolism by liver, but 70-75% of the drug is accounted for in unchanged form in urine. Dose in liver disease Same as for cephalothin.

Nitrofurantoin: Metabolism by liver. 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. Significant liver tissue levels and bile levels,similar to plasma. 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.

Metronidazole and related drugs (tinidazole, ronidazole): are sometimes used in patients with hepatic disease because of the anaerobic spectrum. They have been safe drugs when prescribed according to standard dose recommendations, but when doses have been exceeded, problems may arise. The most serious problem caused by metronidazole has been attributed to CNS toxicity and include seizures, ataxia, nystagmus, tremors, and rigidity.

Fluoroquinolones: The fluoroquinolones (enrofloxacin, marbofloxacin, orbifloxacin, difloxacin) have had a good safety record 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

Glucocoritcoids : Prednisolone 0.125 – 1mg/kg/day initially , then decrease dose to alternate day therapy over 4-6 weeks Prednisone is metabolized to liver to active from , prednisolone

Advantages

Improved well – being Appetite stimulation

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Anti – inflammatory Immunosuppression Anti- fibrotic

Disadvantages

Superimposed steroid heptopathy Predispose to infection Catabolic

Azathioprine

Alternative drug for immunosuppression,use alone or in combination with steroids 1.0 mg/kg/day in dogs . 0.3 mg/kg/day in cats ; may decrease to alternate day

Colchicine

Used experimentally to reduced hepatic fibrosis 0.03 mg/kg/day PO

Ursodeoxycholic acid

Hydrophilic, beneficial bile salt Alter bile composistion and stimulates bile flow in intra- hepatic cholestsais Modulates immune response in liver Efficancy not yet proven in small animals

Decoppering agents

D – penicillamine & trientine – very slowly chelate copper in circulation and excrete it in urine

Oral zinc acetate to block copper absorption

Vitamin E

Reduced continuation of oxidative damage in chronic hepatitis Supprotive and symptomatic therapies Control HE an aid hepatic regeneration

Diet

Protein restriction and modification Rationale= reduced blood NH3 and aromatic amino acids, yet permit

regeneration Protein sources Pedigree hepatic support diet Home cooking : cottage cheese , vegetable protein (plus pasta or rice)

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Feed 1.4 – 2.2 gm protein /kg/ day in 3-4 small meals If hypoalbuminaemic, increases protein amount useless encephalopathic

Carbohydrates

Easily digestible – eg. Boiled rice

Fats

Increased amount may aggravate encephalopathay,Some necessary for palatability,Provide essential fatty acids, fat – soluable vitamins

Vitamin/mineral supplementation

Fat – soluble (ADEK) Vitamin B complex In supplementation blocks intentinal copper uptale

Rest and confinement

Increase hepatic blood flow Reduced pain / tenderness associated with liver capsule stretching

TREATMENT OF HEPATIC CRISIS

Hepatic encephalopathy

Identify and treat precipitating causes eg dehydration , GI bleeding Diet Alter intestinal flora Antibiotics Decreases urease – producing bacteria NH3 production Neomycin, metronidazole Lactulose syrup (15-30 ml QID PO – dose variable and empirical) Artificial disaccharide Modified by colonic bacteria – lactate and acetate – acidification – traps

NH3 as NH4 ( not absorbed)

Ascites and oedema

Low sodium diet and Diuretics Paracentesis to remove ascetic fluid only for control of dyspnoea and

discomfort

*****

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CLINICAL MANAGEMENT OF RENAL IMPAIREMENTS

M.VIJAYKUMAR

The kidneys have 3 basic types of function: 1) excretory, 2) regulatory, and 3) biosynthetic. The excretory function involves elimination of toxins from the body by way of glomerular filtration and tubular secretion. Elimination of urea, creatinine, and other nitrogenous waste products of protein catabolism are excretory functions. Excretory failure is often recognized as azotemia.

Loss of these renal functions results in a narrowing of the physiologic range over which the kidneys are able to adapt. For example, loss of urine concentrating ability (regulatory failure) leads to obligatory increases in water intake. The failing kidneys have impaired ability to adapt to extremes (high or low) in electrolyte intake. This limited ability of the failing kidneys to adapt to variations in intake directly relates to therapeutic plans.

Acute Kidney Disease: Causes

Some of the common causes of acute kidney failure are as follows:

Trauma such as a physical injury that leads to rapid fall in blood pressure. An accident that causes significant amount of blood loss.

Consumption of rat poison, turpentine or external toxins such as antifreeze, pesticides and certain plants.

Illnesses related to heart result in lack of, or inadequate supply of blood to the dog's kidneys, which in turn can lead to accumulation of toxins in the bloodstream.

Chemotherapy drugs, anti-fungal medicines, and certain antibiotics. Urinary tract infections Bladder or urinary tract obstructions due to kidney stones.

Acute Kidney Disease: Symptoms The most commonly observed symptoms of acute kidney failure are as follows:

Dehydration Pain around kidneys Arched back and stiff legged gait Difficulty in urinating Vomiting

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Dark tongue Little or no urine output

Chronic Kidney Disease: Causes There are a number of factors responsible for causing chronic kidney disease. They are:

Diabetes Physical trauma Abnormally developed kidneys. Cysts in kidneys. Autoimmune diseases An unbalanced or poor quality diet can cause chronic canine kidney disease.

Food that has high phosphorous content can be problematic for dogs. If the food contains insufficient amount of calcium, then the kidneys are unable to remove the phosphorous effectively. This leads to formation of kidney stones, which eventually leads to kidney failure. Very high doses of vitamin D can also have harmful effects on the dog's kidneys.

Chronic kindey disease symptoms:

Increased thirst (the dog consumes greater amount of water than normal). Frequent urination, that is pale in color. Nausea and fatigue Depression Constipation Weight loss Weakness and inability to tolerate exercises Tendency to bruise or bleed easily Bad breath (smells like ammonia)

LABORATORY EXAMINATION

Urinalysis: In renal failure diagnosis,urinalysis is of prime importance.urine collection may be made during the spontaneous micturition or manual compression of the bladder or catheterization or by cystocentesis.fresh smaple of urine is always preferred for analysis

Macroscopic urinalysis:

The first part of a urinalysis is direct visual observation. Normal, fresh urine is pale to dark yellow or amber in color and clear. Normal urine volume is 750 to 2000 ml/24hr.

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Turbidity or cloudiness may be caused by excessive cellular material or protein in the urine or may develop from crystallization or precipitation of salts upon standing at room temperature or in the refrigerator. Clearing of the specimen after addition of a small amount of acid indicates that precipitation of salts is the probable cause of turbidity.

A red or red-brown (abnormal) color could be from a food dye, eating fresh beets, a drug, or the presence of either hemoglobin or myoglobin. If the sample contained many red blood cells, it would be cloudy as well as red.

pH

The glomerular filtrate of blood plasma is usually acidified by renal tubules and collecting ducts from a pH of 7.4 to about 6 in the final urine. However, depending on the acid-base status, urinary pH may range from as low as 4.5 to as high as 8.0.

Specific Gravity (sp gr)

Specific gravity (which is directly proportional to urine osmolality(solute concentration) measures urine density, or the ability of the kidney to concentrate or dilute the urine over that of plasma. Specific gravity between 1.002 and 1.035 on a random sample should be considered normal if kidney function is normal. If sp gr is not > 1.022 after a 12 hour period without food or water, renal concentrating ability is impaired and the patient either has generalized renal impairment or nephrogenic diabetes insipidus. In end-stage renal disease, sp gr tends to become 1.007 to 1.010.

Protein

Normal total protein excretion does not usually exceed 150 mg/24 hours or 10 mg/100 ml in any single specimen. More than 150 mg/day is defined as proteinuria. Proteinuria > 3.5 gm/24 hours is severe and known as nephrotic syndrome.

Glucose

Less than 0.1% of glucose normally filtered by the glomerulus appears in urine (< 130 mg/24 hr). Glycosuria (excess sugar in urine) generally means diabetes mellitus.

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Ketones

Ketones (acetone, aceotacetic acid, beta-hydroxybutyric acid) resulting from either diabetic ketosis or some other form of calorie deprivation (starvation), are easily detected using either dipsticks or test tablets containing sodium nitroprusside.

Nitrite

A positive nitrite test indicates that bacteria may be present in significant numbers in urine. Gram negative rods such as E. coli are more likely to give a positive test.

Leukocyte Esterase

A positive leukocyte esterase test results from the presence of white blood cells either as whole cells or as lysed cells. Pyuria can be detected even if the urine sample contains damaged or lysed WBC's.

MICROSCOPIC URINALYSIS

Red Blood Cells

Hematuria is the presence of abnormal numbers of red cells in urine due to: glomerular damage, tumors which erode the urinary tract anywhere along its length, kidney trauma, urinary tract stones, renal infarcts, acute tubular necrosis, upper and lower uri urinary tract infections, nephrotoxins, and physical stress.

The presence of dysmorphic RBC's in urine suggests a glomerular disease such as a glomerulonephritis.

White Blood Cells

Pyuria refers to the presence of abnormal numbers of leukocytes that may appear with infection in either the upper or lower urinary tract or with acute glomerulonephritis. Usually, the WBC's are granulocytes. If two or more leukocytes per each high power field appear in non-contaminated urine, the specimen is probably abnormal.

Casts

Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). The proximal convoluted tubule (PCT) and loop of Henle are not locations for cast formation. The factors which favor protein cast formation are low

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flow rate, high salt concentration, and low pH, all of which favor protein denaturation and precipitation, particularly that of the Tamm-Horsfall protein.

In end-stage kidney disease of any cause, the urinary sediment often becomes very scant because few remaining nephrons produce dilute urine.

Bacteria

Generally, more than 100,000/ml of one organism reflects significant bacteriuria. Multiple organisms reflect contamination. However, the presence of any organism in catheterized or suprapubic tap specimens should be considered significant.

Crystals

Common crystals seen even in healthy patients include calcium oxalate, triple phosphate crystals and amorphousphosphates

Type of Stone Frequency Calcium oxalate (or phosphate) 75% Magnesium ammonium phosphate (struvite, or "triple hosphate") 12% Uric acid 6%

Summary of Diagnostic Tests Indicated for Renal Failure Patients

Evaluation Purpose Blood urea nitrogen Assess degree of azotemia Serum Creatinine To establish the diagnosis & measure intrinsic renal function Urinalysis To establish diagnosis & identify renal complications Urine culture To rule-out urinary tract infection Complete blood count To detect anemia of renal failure & inflammatory

complications Serum sodium To detect hyponatremia or hypernatremia Serum potassium To detect hypokalemia or hyperkalemia Serum total carbon dioxide To assess metabolic acid-base status Serum chloride Useful in assessing serum tCO2 and Na concentrations Serum phosphorus To detect hyperphosphatemia Serum calcium To detect hypercalcemia or hypocalcemia Serum albumin & total protein concentrations

To assess nutritional status

Body weight To assess nutritional status Protein:creatinine ratio (if proteinuric)

To assess magnitude of proteinuria

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Blood pressure To evaluate for hypertension Fundic examination To evaluate for hypertensive retinopathy or other systemic

diseases Survey abdominal radiographs

To rule-out urolithiasis, structural lesions, or urinary obstruction

Renal ultrasound To structurally evaluate the kidneys to establish a primary diagnosis

Renal Biopsy To structurally evaluate the kidneys to establish a primary diagnosis

CONSERVATIVE MEDICAL MANAGEMENT OF RENAL FAILURE:

Conservative medical management of CKD consists of supportive and symptomatic therapy designed to correct deficits and excesses in fluid, electrolyte, acid-base, endocrine, and nutritional balance and thereby minimize the clinical and pathophysiological consequences of reduced renal function. Goals of conservative medical management of patients with chronic primary renal failure are to: (1) ameliorate clinical signs of uremia, (2) minimize disturbances associated with excesses or losses of electrolytes, vitamins, and minerals, (3) support adequate nutrition by supplying daily protein, calorie, and mineral requirements, and (4) modify progression of renal failure. Conservative medical management is most beneficial when combined with specific therapy directed at correcting the primary cause of renal disease.

Conservative Medical Management of Renal Failure in Dogs and Cats

Clinical or Laboratory Abnormality Treatment Options Progression of CKD Diet therapy Azotemia/uremia Diet therapy Polyuria and polydipsia Free access to water

Consider diet therapy Dehydration (prophylaxis) Free access to water

Avoid stress Canned Food Supplemental fluid therapy (?)

Metabolic acidosis Therapeutic alkalinization Anemia of CKD Erythropoietin therapy

Supplemental Iron Transfusion therapy Androgen therapy

Hyperphosphatemia Diet therapy Intestinal phosphate binding agents

Hypocalcemia Oral calcium supplements Calcitriol therapy

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Renal osteodystrophy Minimize hyperphosphatemia(prophylaxis/ treatment) Oral calcium supplements Calcitriol therapy

Systemic hypertension Sodium restriction Antihypertensive drug therapy

Drug reactions/overdosage Avoid nephrotoxic drugs Adjust dosages according to renal function

Urinary tract infection Monitor for infection Antibiotic therapy

Ameliorating clinical consequences of excretory failure:

Reducing protein intake:Controlled reduction of non-essential proteins wil result in decreased production of nitrogenous wastes with consequent amelioration of clinical signs of uremia

Indications of diet therapy:

Dietary Component Change from typical maintenance diets Protein quantity Reduced Protein quality Increased Phosphorus Reduced Sodium Reduced Fatty acids Enhanced omega 3:omega 6 PUFA ratio Caloric density Enhanced Fiber Enhanced

Enhancing diet palatability:

Changes in the diet: changes in the diet should be made gradually over a period of one – two weeks.Warming of food improves palatability.warm water should be added to dry feed.fresh aromatic feed should be offered.

Food aversion : occurs if nauseated patients are force fed.If painful sample collection or drug administration is associated with feeding unpalatable drugs should not be mixed with regular feed or water.

Flavoring agents: agents like animal’s fat, butter,dehydrated cottage cheese,garlic etc.enhance palatability

Modifying feeding patterns and environment: Animal should be fed frequently with small quantities of food, placing palatable food in the patients mouth or paws may stimulate a licking response

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Pharmacological appetite stimulants

Anabolic steroids: even though these drugs are claimed to improve the appetite, no data is available to support this in renal failure

Corticosteroids: there is no data to support longterm beneficial effect in ureamic dogs and cats

Benzodiazepenes: diazepam stimulates appetite in various species.But only marginal success in renal failure patients

Diazepam : 0.2mg/kg i.v with a maximum of 5mg/kg/patient,given twice a day,PO or i.m can also be given

Oxazepam: used only for oral administration.2.5mg/patient,not suitable for longterm usage

Modification of drug dosages: nephrotoxic drugs that require renal excretion should be avoided in patients with renal failure

Avoiding clinical consequence of regulatory failure:

Hyperphosphatemia is managed by restricting dietary phosphorus intake , oral administration of intenstinal phosphorous binding agents or a combination of these methods . The ultimate aim is phosphoros restriction . Modified protein diets designed for dogs with renal failure may contain as little as 0.13 to 0.28 % phosphorous on a dry matter basis and provide about 0.3 to 0.5 mg/kg phosphorous (Typical commercial dog food contain 1 to 2 % phosphorous on DM basis and 2.7 mg/Kcal phosphorous ) Modified protein diet for cats contains 0.5 % phosphorous on DM basis and 0.9 mg/Kcal of phosphorous ( Typical commercial food contains 1-4 % phosphorous on DM basis and 2.9 mg/Kcal phosphorous).

Intestinal binding agents

These render ingested phosphorous contained in the saliva , bile and intestinal juices unabsorable. These agents are administered by mixing food or just before meal. Aluminium containing intestinal phosphorous binding agent include aluminum hydroxide, aluminum carbonate and aluminum oxide, Dose 30 to 90 mg/kg/day . Available as antacid preparation in liquid, tablet or capsule forms, Sucralfate, a complex polyaluminium hydroxide salt of sulfate used primarily for gastro intestinal ulceration is also effective than aluminum based agents, excess usage may lead to hypercalcaemia Calcium acetate is the most effective and given at a dose rate of 60 –

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90 mg/kg/day. Calcium carbonate is given at a dose rate of 90-250mg/kg, calcium based agents must be administred with feed both to enhance phosphorous binding and to minimize absorption of calcium.

Hypokalemia

Potassium replacement therapy is indicated for cats with hypokalemia (serum potassium concentration less than 4 mEq/1r) even in the absence of clinical signs of hypokalemia

Potassium gluconate 2-6 mEq/cat/day as powder , tablet , gel or elixir .Patassium citrate can also be given.

Routine supplementation of low oral doses of potassium (2 meq/day ) has been recommended for all cats with chronic renal disease. Diets that are acidifying and restricted in magnesium content may promote hypokalemia and hence be avoided in cats with chronic renal failure .

Fluid should be administred such as potassium is delivered intravenously at a rate less than 0.5 meq/kg/hr

Metabolic acidosis : Alkalinization therapy designed to correct metabolic acidosis is an important component in the management of patients with CRF. Oral alkalinization therapy is indicated when serum bicarbonate concentration decline to or below 17 mEq/1r. Oral sodium bicarbonate 8-12 mg/kg 8-12 hrs is commonly used

Dehydration: Fresh clean unadulterated water should be available in adequate quantities at all times. The composition of fluids selected for chronic parentral administration should provide free water as well as electrolytes for maintenance (Lactated ringers solution supplemented with KCL).

Arterial hypertension : Blood pressure may be measured directly by cannulation of an artery or indirectly by doppler ultrasonography or oscillometry . Hypertension exists when mean arterial blood pressure exceeds 152mm of Hg in dogs and 139mm in cats.160/95 in dogs and 180/120 in cats warrant a diagnosis of hypertension. Therapy should be directed at counteracting the effect of extracellular fluid volume and vasoconstrictor effects of angiotension II and not epiephrine which is important in arterial hypertension associated with CRF. There are non pharmacologic and pharmacological therapies to reduce hypertension.

Non – Pharmacologic therapy:

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Dietary sodium restriction: Daily sodium intake should be reduced to 0.1 to 0.3 percent of the diet on a dry matter basis ( 10-40 mg/kg/day) without reduction of sodium intake administration of some anti – hypertensive drugs such as beta adrenergic receptor antagonists and arteriolar vasodilators ; may lead to sodium retention extra cellular fluid volume expansion attenuation of anti hypertensive effects .

Protein restriction : May limit or prevent renal hypertensive injury by reducing intraglomerullar capillary pressures.

PHARMACOLOGIC CONSIDERATIONS

Renal insufficiency can markedly alter one or more of the pharmacokinetic parameters of a drug including oral bioavailability, volume of distribution, drug binding to plasma proteins, and most importantly the rates of metabolism and excretion, i.e., drug clearance. To minimize drug toxicity and maximize therapeutic benefits, it is often necessary to adjust drug dosage in proportion to the degree of renal efficiency

Dose adjustment may involve one or a combination of the following measures:

1. Extension of the dosing interval. 2. Reduction of the maintenance dose.

3. Administration of a loading dose.

4. Monitoring serum drug levels.

To maintain a therapeutic level and, at the same time, avoid drug accumulation and toxicity in a patient with reduced renal function, the clinician must consider reducing the size of the maintenance dose or the dosing frequency or both. In general, this reduction should also be proportional to the degree of renal impairment but should also take into account adaptive or compensatory changes in the metabolism and excretion of the drug through non renal routes.

Commonly used drugs in the treatment of renal failure :

Class Generic name Dosage IndicationsAngiotensin converting enzyme inhibitor

Enalapril 0.25mg/kg PO q 12-24 h (D)

Systemic hypertension

Appetite stimulant Diazepam 0.2mg/kg PO,IV q 12-24 h (D,C)

Appetite stimulant

Oxazepam 0.2-0.4mg/kg PO,q12-24 h (D,C)

Appetite stimulant

Calcium channel blocker Amlodipine 0.625-1.25mg PO q 24 h (C)

Systemic hypertension

Dopamine antagonist Metaclopropa 0.2-0.4mg/kg q 6-8h Antiemetic/

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mide SQ,PO (D,C) gastrokineticGastric protectant Sucralfate 0.5-1.0g q 8-12 h PO

(D)Uremic gastropathy/phosphate binding agent

H2 receptor antagonists Cimetidine 5mg/kg q 8-12 h PO,IV (D,C)

Uremic gastropathy

Ranitidine 2-2.5g/kg q 2 h PO (D,C)

Uremic gastropathy

Famotidine 0.5mg/kg q 24h IV,PO (D,C)

Uremic gastropathy

Intestinal phosphate binders

Aluminium hydroxide gel,Al.carbonate gel

10-30mg/kg q 8h ,PO (D,C)

Phosphate binding agents

Calcium acetate

20-30mg/kg q 8h ,PO (D,C)

Phosphate binding agents

Calcium carbonate

30-50mg/kg q 8h ,PO (D,C)

Phosphate binding agents

Iron supplements Ferrous sulphate

100-300mg/d PO,(D)

Potassium supplements Potassium gluconate,potassium citrate

2-6mEq/d PO,(C)

Proton pump inhibitor Omeprazole 0.7mg/kg q 24h PO (D,C)

Ureic gastropathy

Recombinant human erythropoietin

Erythropoietin 100U/kg 3times weekly SQ (D,C)

Sertonergic agonist Cisapride 0.1-0.5mg/kg PO q 8-12h (D,C)

Antiemetic/Gastroprokinetic

Synthetic prostaglandin Misoprostol 2-5µg/kg q 8h PO(D) Uremic gastropathy Vitamin D Calcitrol 2.5-3.5ng/kg q 24h PO

Antimicrobial Selection: Susceptibility testing should be performed on all urinary bacterial isolates from patients with UTI. As a result of renal excretion, many antimicrobial agents attain substantially higher concentrations in urine than in blood. The drug selected should be administered frequently enough to maintain inhibitory concentrations in urine and for sufficient time to eliminate the infecting agent from the urinary tract. Decisions concerning treatment for superficial infections of the lower urinary tract urothelium can be based on urine antimicrobial concentrations. However, it is necessary to select agents that attain high concentrations in serum and urine to eradicate deep seated infections such as pyelonephritis or prostatitis. Fluoroquinolones are most likely to achieve therapeutic concentrations in renal tissue in patients with pyelonephritis. Because of the blood prostatic fluid barrier is expected to be intact in chronic prostatitis, an appropriate antimicrobial which will attain therapeutic

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concentrations in prostatic secretions should be selected(e.g.quinolones,trimethoprim-sulfonamidecombinations,chloramphenicol,clindamycin,erythromycin,oleandomycin).

Protocol for Therapy and Follow-up of UTI: Therapy is successful only if the urine does not contain any pathogenic organisms. Treatment is ineffective and relapse will occur if the bacterial colony count has only been reduced. It is recommended that acute, uncomplicated UTIs and some reinfections be treated for a period of 10 to 14 days whereas chronic or persistent UTI should be treated for at least 4 to 6 weeks. Administration before bedtime (or other extended interval of confinement) assures that the urinary bladder fills with urine containing a high concentration of the antimicrobial agent.During long-term therapy, the effectiveness of prophylactic therapy should be confirmed by urine cultures performed by cystocentesis about every 4 to 6 weeks. If urine cultures are negative, therapy is continued.Anitmicrobials contraindicated in renal failure include amphotericin B, carbenicillin, flucytosine, nalidixic acid, nitrofurantoin, polymyxins etc.

Antimicrobials doses in renal ailments :

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S.No Name of the drug Dosage (total dose) Dosing interval

Aminoglycosides

1 Amikacin 1.5–2.5 mg/kg q 24–48 h

2 Gentamicin 0.34–0.51 mg/kg q 24–48 h

3 Streptomycin 7.5 mg/kg (max. 1 g) q 72–96 h

4 Tobramycin 0.34–0.51 mg/kg q 24–48 h

β -lactams:cephalospoins (1st generation)

5 Cefadroxil 0.5 g q 36 h

6 Cefazolin 1–2 g q 24–48 h

7 Cephalexin 0.25–0.5 g q24–48 h

β -lactams:cephalospoins (2nd generation)

8 Cefotetan 1–3 g q 48 h

9 Cefoxitin 0.5–1.0 g IV q 24–48 h

10 Cefuroxime 0.25–0.5 g po

0.75 g IV

q24 h

q 24 h

β -lactams:cephalospoins (3rd generation)

11 Cefoperazone 1 g

2 g

q 12 h

q 4 h

12 Cefotaxime 1–2 g q 24 h

13 Ceftazidime 0.5 g q 24–48 h

14 Ceftizoxime 0.5 g q 24–48 h

15 Ceftriaxone 1–2 g q 24 h

β -lactams:cephalospoins (4th generation)

16 Cefepime 0.25–1 g q 24 h

β -lactams:penicillins

17 Amoxicillin 0.25–0.5 mg q24 h

18 Amoxicillin clavulanate 0.25–0.5 mg q24 h

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19 Ampicillin 0.5-2.0 g q 12-24 h

20 Ampicillin-sulbactum 1.5–3.0 g q 24 h

21 Dicloxacillin 0.125–0.5 g q 6 h

22 Nafcillin 1–2 g q 4 h

23 Oxacillin 1–2 g q 4 h

24 Penicillin G 0.5–2 million units q 4-6 h

25 Penicillin G benzathine 1.2 million units IM x 1 dose

26 Penicillin G procaine 0.6 million units q 12 h

27 Piperacillin 3–4 g q 12 h

28 Ticarcillin 1–2 g q 12 h

Other β lactams

29 Aztreonam 0.5 g q 8 h

30 Ertapenem 0.5 g q 24 h

31 Imipenem 0.125–0.5 g q 12 h

32 Meropenem 0.5 g q 24 h

Fluoroquinolones

33 Ciprofloxacin 0.5–0.75 g po q 24 h

34 Gatifloxacin 0.2 g q 24 h

35 Gemifloxacin 160 mg q 24 h

36 Levofloxacin 0.25–0.5 g q 48 h

37 Moxifloxacin 0.4 g q 24 h

38 Norfloxacin 0.4 g q 24 h

39 Ofloxacin 0.1–0.2 g q 24 h

Macrolides

40 Azithromycin 0.5gonday1,then 0.25g po q 24 h x4 days

41 Clarithromycin 0.25–0.5 g q 24 h

42 Dirithromycin 0.5 g q 24 h

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43 Erythromycin 0.25 g q 6 h

Sulfonamides and Trimethoprim

44 Sulfisoxazole 1.0 g q 12-24 h

45 Sulfamethoxazole 1.0 g q 12-24 h

46 Trimethoprim 0.1 g q 24 h

Tetracyclines

47 Doxycycline 0.1 g q 12 h

48 Minocycline 0.1 g q 24 h

Others

49 Clindamycin 0.15–0.45 g p.o or 0.6-0.9 g IV

q 6 -8 h

50 Chloramphenicol 0.25–1.0 g IV q 6 h

51 Metronidazole 3.75mg/kg q 6 h

52 Quinupristin 7.5mg/kg q 8-12 h

53 Rifampin 0.3-0.6g q 24 h

54 Spectinomycin 2g IM single dose

55 Vancomycin 0.5-1.0g IV q wk

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RATIONAL USE OF HORMONES IN ANIMAL PRODUCTION

MAHESH S.DODAMANI

Hormone(s), either alone or in combination with other therapeutic agents have been employed by veterinarians, often with varying success. The clinical utility of hormone(s) can be best harvested only if, its requirement is based upon perfect clinical judgement of the case presented with uterine disorder or the endocrine dysfunction. Judicious use of hormone(s) can be a substitute for conventional antimicrobial therapy in most of the post-partum infections of the uterus. Hormone(s) therapy alone or mostly as a adjuvant to antimicrobial therapy is

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beneficial in retention of placental membrane (RFM), post-parturient endometritis(PPE), pyometra and metritis

Prostaglandins (PGF2µ): Basically, PGF2µ possess luteolytic and spasmogenic and extra-uterine(pituitary) properties. The practicing veterinarian must understand progesterone dependent and independent properties of prostaglandins before exploiting prostaglandins(PGs) in post-partum cows/buffaloes. Prostaglandins are found more effective in causing uterine evacuation, hence useful in metritis and pyometra. However, uterine infections with systemic involvement must be treated with suitable antibiotic in additions to PGs. Persistent of residue corpus-luteum is one of the factors for unsuccessful treatment of post-partum infections of the uterus. Further, fluid/pus within the uterine lumen are also responsible for preventing the natural release of PGs from the endometrium. There is also possibility that improper intra-uterine deposition of drug formulation or eve manipulation would damage the endometrium and thereby prevents the release of PGF2a . Knocking down the corpus-luteum (if present) by PGs would favor estrogenic environment in the uterus, which would be a favorable for local defense (immune) mechanisms.

Generally, synthetic or semi-synthetic analogues of PGF2a are preferred over natural by virtue of their luteolytic potency as well as minimal side effects (see table for further details).

Oxytocin and Estrogens:

Exogenous administration of oxytocin (20 IU, i.v or more effectively as continuous, slow intravenous infusion) can also be employed for its ecbolic actions, but optimal response cannot be anticipated unless uterine microenvironment is sensitized with estrogen. Therefore, the benefit of oxytocin is questionable when used after 24-48 hour of calving for expulsion of RFM. Under normal circumstances, oxytocin administration favors uterine involution, therefore judicious use of estrogen and oxytocin is beneficial so as to prevent the possible uterine infection and reduce the inter-calving period.

Estrogens have little or no effect on the rate of separation of fetal cotyledons and maternal caruncles and therefore of little value if it is used for expulsion of RFM. However, estrogens increase the uterine tone and muscular activity, relax cervix and improves blood circulation to uterus. Therefore, they are quite useful either: (i) - to augment the absorption of locally (intra-uterine) administered antimicrobial agents or (ii) - to remove corpus-luteum(C.L) that exists during pyometra. Infact, PGs or estrogen is preferred over manual removal of C.L, because there is less risk to cows.

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Estrogens (Oestradiol benzoate/-valerate/-cypionate) may be used intramuscularly @ 5-10mg/cow to regress the C.L as well as to expel the uterine contents (pyometra). If fails, the recommended dose may be repeated at 2 or 3 days interval. Administration of Oestradiol benzoate/-valerate/-cypionate (3-5mg, i.m) in cyclic cows increases the absorption of antibiotics like benzyl penicillin following intrauterine deposition by virtue of increased blood flow or increases in capillary permeability. Excessive use of estrogens must be avoided as this may lead to extension of infection through the oviduct and may predispose ovarian adhesions.

Gonadotropin releasing hormone (GnRH): Often veterinarians succumb to GnRH therapy in order to overcome extended long standing post-partum anovulatory anestrous in cattle/ buffaloes, following one or the other method of intra-uterine treatments without documenting the uterine infection. Metabolic overload (eg.lactation), micronutrient deficiency, thermal stress, lameness(corticosteroid), delayed involution of uterus, drug resistant pathogens in the uterus are some of the important reasons for long standing cases of anovulatory anestrous. GnRH administration in the intermediate period improves fertility in cows with incomplete uterine involution, but not in normal cows.

The veterinarian must understand that the endocrine dysfunction is one among the several cause of repeat breeding in animals, and therefore their utility in the clinics without documenting the hormonal milieu becomes empirical treatment. Often such clinical judgment would lead to more complicated situations rather than clinical cure from the endocrine dysfunction.

Suggested antimicrobial/antifungal agents for intra-uterine administration

Drug Dose Remarks

Amikacin sulfate 2g Gm -ve

Amphotericin-B 50-200mg Dilute with sterile water, do not use systemic -nephrotoxic

Amoxycillin trihydrate

1-3g May irritate endometrium

Carbencillin 2-6g May irritate endometrium, against

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Psedomonas sps.

Gentamicin SO4 0.5-3g Buffer with sodium bicarbonate, Gm-ve, 30ml, Streptococci infection

Kanamicin SO4 1-3g Spermatocidal, E.coli and not effective against other Gm-ve organisms

Neomycin SO4 3-4g E.coli

Polymixin-B 10,000-1x106 IU

Psedomonas, Do not use systemic

Tricarcillin 1-6g Psedomonas, Klebsiella sps., Broad spectrum

Clotrimazole 300-600g Every 2-3 days for 12 days, Candida sps.,

Miconzole 500mg Yeasts

Commercial preparations of hormone(s) and recommended dosage protocol in cows

Trade name Dose and Route Remarks

Receptal Ò 2.5ml; i.m, iv(0.01mg/cow) GnRH analogue, each ml contains 0. 004mg buserelin

FertagylÒ 1.0ml; im;iv GnRH analogue

CystorelinÒ 2.0ml; im;iv GnRH analogue

ChorulonÒ 1500-3000 I.U,im hCG

CorioganÒ 1500-3000 I.U,im hCG

CorionÒ 1500-3000 I.U,im hCG

Luteinizing hormone

25mg, slow iv Caution about adverse effects

JuramateÒ 2.0ml;im;sc (500mg) Synthetic PGF2µ analogue

Tt. for luteal cysts

SynchromateÒ 2.0ml; im (500mg) Synthetic PGF2µ analogue

Tt. for luteal cysts

LutalyseÒ 5.0ml; im (25mg) Natural PGF2µ

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Tt.. for luteal cysts

ClostenolÒ 2.0ml; im (500mg) Synthetic PGF2µ analogue

Tt. for luteal cysts

ProsolvinÒ 2.0ml; im (15mg) Semi-synthetic PGF2µ analogue

IlirinÒ 3.5ml (iv); 5.0ml(sc)

(max: 0.75mg/cow)

Synthetic PGF2µ analogue

Tt. for luteal cysts

DuraprogenÒ 40mg daily, im for 7days + Oestadiol benzoate (5mg,im) OR GnRH(250mg,im) on progesterone withdrawal

17-µ-hydroxy progesterone caproate

Note: Not a ideal method of progesterone delivery for induction of estrus

Proluton depotÒ -do- -do-

VetaprogenÒ -do- -do-

CrestarÒ 3mg norgestomet (a progestogen) & an injection (2ml) containing 3mg norgestomet & 5mg oestardiol benzoate to be given on removal of ear implant

Management of anestrous

Synchromate-BÒ 6mg norgestomet + 5mg oestradiol valerate

Management of anestrous

CIDRÒ Each onsert ccontains 1.38gm progesterone

Management of nestrous

Hormonally-active substances used in animal production :

Substances Dose levels FormMain use - Animals

Oestrogens alone: 10–20 mg/day feed additive steers, heifersDES 30–60 mg/day implant steersDES   oil solution veal calves

DES 12–60 mg implantsteers, sheep, calves, poultry

Hexoestrol 12–36 mg implant steers, sheep

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Zeranol      Gestagens alone: 0.25–0.50 mg/day heifers  Melengestrol acetate      

Androgens alone: 300 mg implantheifers, culled cows

TBA      Combined preparations:

25mg-120 mgimplant calves

DES+Testosterone   feed additive swineDES+Methyl-testosterone

30–45mg-300 mgimplant steers

Hexoestrol+TBA 36mg-300 mgimplant steers

Zeranol+TBA 20mg-140 mgimplant

bulls, steerscalves, sheep

Oestradiol-17β+TBA 20mg-200 mgimplant heifers, calves

Oestradiol-17β benzoate +Testosterone propionate

20mg-200 mgimplant steers

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THERAPEUTIC MANAGEMENT OF EPILEPSY AND SEIZURES

SANTOSH .P. SARANGAMATH

Seizures are a clinical signs which occurs due to cerebral dysfunction, which originates from structural (Trauma or Tumor) or functional (Physiological or Metabolic) causes. Seizure, Convulsion, fits are all synonyms for abnormal electrical discharge of brain cells which occurs all of a sudden and stops suddenly. Whereas, epilepsy is somewhat confusing in the sense that, recurrent seizures will be there but that occurs due to some other disease process or primarily it is unrelated to brain disorder. Further epilepsy is classified into primary epilepsy also called as Idiopathic, Genetic, True or inherited epilepsy where there is a genetic involvement is recognized. Secondary epilepsy also called as acquired or symptomatic epilepsy, is due to residual brain damage due to trauma, encephalitis, hydrocephalus...Etc.

STAGES OF SEIZURE:

A seizure has 4 stages, first prodrome stage which lasts for several hours to days, second aura or preictal stage often it is not recognized in animals, Third actual seizure or ictus stage which lasts for seconds to few minutes and Fourth postictal stage which lasts for several minutes to hours or sometimes goes days together without notice.

CLASSIFICATION OF SEIZURES:

Seizure can be classified into Generalized, Partial or Partial with secondary generalization. Generalized seizures are most common type of seizures encountered in dogs and cats. In generalized seizures neurons on both sides of the cerebral cortex discharge simultaneously to produce symmetric involvement of the body. There are several forms of generalized seizure; common form is tonic-clonic seizure where the pet falls suddenly, losses consciousness, and manifests involuntary extension of limbs followed by paddling, chewing motion, pupillary dilatation and salivation. Defecation and urination may also occur during or after the seizure.

During Partial seizure, only one portion of the cerebral cortex is spontaneously discharge electrical activity, therefore clinical appearance of seizure vary depending on the function of the involved area. If the focus of the seizure is on the left motor cortex, then involuntary muscle jerking is observed in the right side of the body. Partial with secondary generalized seizure; some of the signs include at the beginning pet exhibits

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turning of head towards at one side, lifting of one leg, unilateral facial twitching followed by generalized seizures.

Neurological examination:

Soon after the seizure activity neurological examination will be abnormal. Weakness, blindness, behavioral changes, asymmetric neurological changes like, circling to one side, weakness at one side of the body… etc will helps to localize the lesion to one side of the brain.

OTHER LABORATORY TESTS :

CBC (complete Blood count) for e.g.: in lead poisoning, one can see nucleated RBC’s, low/normal PCV, Basophilic stippling. In chronic disorders or in fungal diseases, monocytosis may be observed and leucocytosis with shift to left indicate inflammatory response and perhaps the infectious cause of seizure.

SERUM CHEMISTRY:

Elevated liver enzyme levels may be observed in liver disease as a potential cause of seizure. Severe electrolyte abnormalities may indicate seizure activity. Also severe hypoglycemia in a non diabetic patient may indicate hypoglycemia induced seizure activity.

Urinalysis: calcium oxalate crystals may be observed in ethylene glycol toxicity patients with seizure activity.

Cerebrospinal fluid analysis (CSF) analysis, skull radiography, EEG, CT, and MRI may provide more information regarding the type and extent of intracranial lesion. Analysis of CSF should include, RBC, WBC count, cytology, protein estimation and culture for aerobic, non aerobic and mycotic infection. CSF analysis also includes measuring titers for CD, Toxoplasmosis, Cryptococcosis. Specialized imaging techniques like CT and MRI are becoming widely used and offer best means of diagnosing and locating brain tumors and infracts.

MEDICAL MANAGEMENT OF SEIZURES OR EPILEPSY IN PETS:

Regardless of the cause, seizures ordinarily can be controlled by the available anticonvulsants. Anticonvulsants are pharmacological agents which stabilize the neuronal membranes and reduce the repetitive burst firing associated with clinical seizures. This is achieved either directly by altering ion conductance and hyperpolarizing the neuronal membrane, or indirectly by enhancing the actions of inhibitory neurotransmitter at neurons, i.e. gamma amino butyric acid (GABA).

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Anticonvulsant therapy is directed towards reducing the clinical signs of the disease and not in treating the underlying etiology. These drugs may improve quality of life in patients but in some cases fails to respond and such patients die due to complications. The decision to begin therapy is based on several factors like, severity of seizures, owner’s dedication and cost of the medicine. The best baseline for taking decision is based on the severity of the problem. For e.g an animal with unacceptable preictal or postictal behavior (aggression) or animal that end up developing status epilepticus or repeated cluster seizures should receive aggressive therapy. Also, with some large breeds of dogs like GSD, Irishsheter, spanials, it is difficult to control seizures with standard anticonvulsants. So, more aggressive therapy is indicated in these breeds.

The goal of anticonvulsant therapy is to reduce the frequency, duration and severity of the seizures while producing minimal side effects. The biological activity of a drug depends on protein binding capacity, degree of ionization, lipid solubility at physiological pH and its rate of elimination. A drug will develop appreciable serum concentration only if it administered at least once every half life. Ideally, serum concentrations should remain constant so that trough concentrations remain within the therapeutic range while peak concentrations do not reach toxic levels. This typically requires administration at least twice during the elimination of half life. Only those drugs with half life greater than 24 hours are suitable for primary control of seizure disorders. This limits the choice for Phenobarbital or primidone in dogs. Dugs with shorter half life may be useful in refractory cases.

INITIAL THERAPY OF DOGS:

Phenobarbitol remains the mainstay of anticonvulsant therapy in dogs. The recommended starting dose is 2.2 mg/kg administered twice daily. Negative side effects include polyphagia, polydipsia, polyurea and sedation, vomiting. These things will settle down after the initiation of treatment for 2 to 3 weeks. More serious complications include bone marrow suppression, hepatotoxicosis and pancreatitis. In dogs administration of phenobarbitol more than 10 mg/kg, twice daily is not recommended because that may reach toxic levels of serum concentration.

Primidone is another analogue of phenobarbitol, administered at the rate of 5 to 10 mg/kg, which is rapidly metabolized into Phenylethylmalonic acid (PEMA) and Phenobarbitol. These chemicals have anticonvulsant activity, but the primidone and PEMA have shorter half lives so not so effective in management in seizures, but sometimes in occasional cases where phenobarbitol failed to respond is well managed with primidone.

In cats, phenobarbitol is administered at the dose of 1 to 2 mg/ kg , the side effects are similar to that of dogs with more pronounced sedation initially.

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Diazepam is another effective anticonvulsant in cats. A dose of 0.25 to 0.5 mg/kg b.i.d. is found be effective as per the literature. Some authors suggest a total dose of 3 to 45 mg per cat.

Primidone in one study in cats reported to be safely used to control seizures at the dosage of 20 mg/kg such drug can be used with caution in cases that have failed to respond for the phenobarbitol.

Phenytoin half life of this drug in cat is reported to be varying from 24 to 108 hours. Because of this kind of variation in half life, dasage has to calculated on an individual basis.

However, about 20 -30 % of epileptic dogs never attain satisfactory seizure control with the above mentioned drugs and are considered refractory to that drug/s. Recent literature reveals many of the common antiepileptic drugs used in people with epilepsy are not acceptable alternatives in veterinary medicine because of lack of efficacy (valproic acid, oral diazepam and lamotrigine- as a potential for causing toxicosis). However, in the past decade several new drugs have promised to improve seizure control and resulted in fewer side effects in people. Several recently published reports describe the treatment of epileptic dogs with these new medicines, thus veterinary medicine is seeing an increase in the options available for managing refractory seizures in digs.

Different clinicians will stick to different protocol/guidelines for initiating therapy, but most commonly, therapy is recommended in an animal that is experiencing more than one seizure in a month or has cluster seizures irrespective of frequency, or has any history of status eppilpticus. Even after giving the conventional epileptic drugs if seizures are not getting controlled-means, in such animal one can include an additional anti epileptic drug ( as a ADD-ON drug) along with routinely used antiepileptic drugs. The following are some of the newer add on antiepileptic drugs.

Felbamate: approved in human beings for use in US, as it has side effects of causing aplastic anemia and hepatotoxicosis, its use is declined. The half life in dogs is 5 to 8 hours, and recommended dosage is 15 to 60 mg/kg every 8 hours. In combination with phenobarbitol it has potential to cause liver and kidney damage, so such animals are to be routinely screened for liver enzyme activity and kidney function tests.

Gabapentin: The half life of the drug in dogs is 2 to 4 hours, so frequent administration is must. It is primarily excreted by kidney in humans and dogs, but in dogs it undergoes partial hepatic metabolism. Dosage is 10-15 mg/kg t.i.d. liquid formulation is also available.

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Pregabalin: limited information is available for this drug as a use for antiepileptic drug in dogs. Dosage is 2 to 4 mg/kg orally every 8 hours has been recommended in dogs.

Zonisamide: is a sulfonamide derived antiepileptic drug; half life is 15 to 20 hours which requires only twice administration. Most of the drug is excreted through kidney and some of it undergoes hepatic metabolism, dosage is 5 to 10 mg/kg orally every 12 hours. It has teratogegic effect so its use in pregnant bitches is to be avoided.

Levetiracetam: It has minimal hepatic metabolism, half life is 3 to 4 hours and recommended dosage is 20 mg/kg every eight hours. Very ideal in controlling the seizures in refractory cases in combination with phenobarbitol or potassium bromide. Desired serum concentration will be achieved with a short time, by intra muscular injection peak concentration of the drug in the serum will be noticed as early as 40 minutes. Thus this drug may be very useful in managing cluster seizures or status epilepticus in dogs.

MANAGING PATIENTS WITH STATUS EPILEPTICUS

The WHO (World Health Organization) defines status epilepticus as “a condition characterized by an epileptic seizure so sufficiently prolonged or repeated at sufficiently brief intervals, so as to produce an unvarying and enduring epileptic condition” from the clinical perspective, status epilepticus is one continuous seizure lasting 30 minutes or more, or a series of multiple seizures within a short period without intervening periods of normal consciousness.

Therapy:

Initially it should be directed towards stopping the seizure and correcting the systemic consequences of seizure. The underlying cause should then be determined so that a more definitive therapy can be instituted.

CONCLUSION:

Seizures should not be considered as a disease entity, but rather an undesirable clinical sign of some other disease. Regardless of the cause, anticonvulsants have provided clinicians with an effective means to control seizures in most patients. As our understanding of the generation of a seizure discharge advances, more specific therapy may become available. Until that time, careful monitoring and client education will provide rewarding results in many cases.

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CLINICAL PROTOCOLS IN VETERINARY ANAESTHESIA

B. V. SHIVAPRAKASH

Surgery in wide range of species and for different organ disorders are being attempted more commonly by field veterinarians. Anaesthesia cannot be same for all surgeries and for all species of animals. This topic aims at discussion and demonstration of anaesthetic protocols for surgery.

Before narrating different anaesthesia combination, an anaesthesian has to follow following steps for successful anaesthesia and surgery.

1. Preoperative evaluation of anaesthetic patient and its preparation.2. Selection of suitable preanaesthetic and anaesthetic agents, route of

administration and equipments.3. Administration and intraoperative monitoring of anaesthesia.4. Monitoring during recovery from anaesthesia.

Step 1: Preoperative evaluation of anaesthetic patient and its preparation.

Objective: To judge patient’s physical status and its ability to withstand stress of anaesthesia and surgery.

Methods :

1. History 2. Physical examination 3. Palpation, percussion, auscultation 4. laboratory examination

The history and physical examination are the best determination of the presence of disease.

Laboratory tests may be undertaken as per the history and signs of the patient.Preanaesthetic history and signalment

A. signalment: i.Age ii.Breeds iii.Sex

B. Body weight

C. Duration of present complaint

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D. Concurrent medication :Aminoglycosides, Chloromphenicol, NSAID’s, Calcium channel blockers, Beta blockers, organophosphates

E. Signs of organs system disease

1. Vomition 2. Diarrhoea3. Polyurea- Polydypsea4. Seizures5. Coughing 6. Exercise intolerance 7. Weight loss

F. Previous allergies and anaesthesia

G. Duration since last feeding

Protocol for Preanaesthetic physical examination in dogs

A. Body weight 1. Obesity 2. Cachexia 3. Dehydration

B. Cardiopulmonary evaluation1. Heart rate and rhythm 2. Auscultation 3. Capillary refill time 4. Mucus membrane colour 5. Pulse character

C. CNS evaluation 1. Temperament2. Seizers, coma 3. Vision, hearing

D. Gastrointestinal evaluation 1. Parasites 2. Abdominal palpation

E. Hepatic evaluation 1. Icterus 2. Abnormal bleeding

F. Renal evaluation 1. Palpate kidney and bladder

G. Integument1. Tumour

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2. Flea infestation H. Musculoskeletal

1. Lameness2. Fracture

Minimum laboratory screening in dogs before anaesthesia i.PCV ii.Adult dogs-BUN iii.Other tests – based on symptoms

List of conditions that should be treated prior to anaesthesia Severe dehydration Anaemia: PCV <20, Albumin: 2g/dl Acid base and electrolytes imbalance PH <7.2, K: < 2.5>6.0 Pneumothorax Cyanosis Oliguria Congestive heart failure

Consideration for selecting an anaesthetic protocol in dogs

1. Procedure to be performed <15 min 15 min to 1 hr > 1hr Major/minor surgery

2. Available equipments, assistance 3. Temperament of the patient4. Physical status5. Breed

Based on history, physical examination and lab examination, patient has to be classified under any one of the following category recommended by American society of anaesthesiologists and anaesthetic agent and procedure has to be selected.

Category Physical status DiseaseI A normal healthy patient Presented for ovario-

hysterectomy, castrationII A patient with mild systemic disease Skin tumour, simple fractureIII A patient with severe systemic disease Fever, anemia, dehydrationIV A patient with severe systemic disease that has

constant threat to lifeUremia,toxaemia, emaciation, high fever

V A moribund patient not expected to survive for 24 hrs

Extreme shock, infection, severe trauma

ANAESTHETIC PROTOCOLS IN DOGS:

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Sedatives and tranquilisers :

Drug Dose (mg/Kg), route Use 1. Ketamine 2-10 IV, IM Not useful alone2. Ketamine+Diazepam or Ketamine+midazolam

5.5 or 0.2 IV 5-10 minutes poor muscle relaxation and analgesia

3. Ketamine + Xylazine 10/0.7-1.0 20-40 minutes

Intravenous anaesthetics in dogs:

Drug Dose (mg/Kg), route Use Thiopental 6-15 IV Short or intermediate Propofol 4-6 IV 5-10 minutes, apnoeaXylazine-Midazolam-butorophanol

0.4/1.0/0.1 IV For several minutes

Anaesthetic protocols in dogs for less than 15 min surgery

1. Thiopental sodium Disadvantage: Full recovery takes upto one hour. I V route is difficult in ferocious dogs.

2. Propofol 3. Diazepam + Ketamine 4. Neurolept analgesia

15 minutes to one Hour (intermediate duration)

1. Thiopental sodium 2. Propofol 3. Diazepam + Ketamine

Above drugs can be used and redosed to effect by administering one third to half of the original dose to prolong the effect more Halothane can also be used.

More than one hour (long duration): Inhalation anaesthesia – Best, Halothane, Isoflurane: Rapid recovery, Even sick and debilitated dogs recover quickly.

INHALATION ANAESTHESIA FOR DOGS:

Inhalation anaesthesia can be initiated without premedication. However, premedication aids in restraint. Induction is most easily accomplished by short acting Barbiturates (Thiopental) or by Propofol.

Vaporizer settings :

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Drug Induction out of circle MaintenanceHalothane 3 1-2Isoflurane 3-4 1.5-3.0

Induction in circle

Halothane 2/3 open 1/2 openIsoflurane 2/3 open 1/2 open

Intraoperative monitoring:

1. Endotracheal intubation soon after induction of anaesthesia 2. Monitoring of cardiovascular system - Heart rate, blood pressure, capillary refill time

3. Respiratory system – respiratory rate 4. Muscle tone, palpebral reflex

Adjust vaporizer setting according depth.

Recovery in dogs

1. Monitoring of patient alert 2. Removal of endotracheal tube 3. Assessment of heart rate, respiratory rate4. Never leave the animal if endotracheal tube in trachea 5. provide oxygen for sick or debilitated dogs or after N2O anaesthesia

HORSES

Standing chemical restraint

1. Chloral hydrate was widely used before the advent of other anaesthetics2. Phenothiazine tranquilizers Acepromazine and Promazine are two commonly used drugs.

Hypotension and priapism are noticed Acepromazine(1%)- 10 mg/ml, used for standing restraint prior to transportation

Because it is long acting, inexpensive and does not produce severe ataxia.

3. Xylazine more commonly used in India can also be administered epidurally.

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4. Detomidine : 80-100 times more potent than xylazine and duration of action is twice longer than xylazine.

Acepromazine – Xylazine

Combination of acepromazine (0.02-0.03 mg/kg) and xylazine (0.2-0.5 mg/kg) has been used to produce improved tranquilization with some reduction of deleterious side effects. The combination produces faster onset and longer duration of action and horse stands more squarely on all four feet. This produces less of a “head-down” posture.

Intravenous anaesthesia in horses:

Preanaesthetics are always given before intravenous anaesthetics. Never anaesthetize an excited horse Intravenous anaesthetics can be safely used for 60 minutes without usin

oxygen.

1. Thiopental: (sedation is must before induction) single bolus produces 15 to 20 minutes anaesthesia. Recovery is acceptable with ataxia dose. Recovery is acceptable if total dose is less than 7 mg/kg.

2. Ketamine : Always used with xylazine

Xylazine - 1.0 mg/kg IV

Ketamine – 2.2 mg/kg IV

Xylazine is given 3 to 5 minutes prior to ketamine. Horse becomes recumbent in 90-120 seconds, is anaesthetised for 15-20 minutes and stands within 30-45 minutes. Recovery is generally smooth.The duration of action can be increased by re-administering half of the original doses of each agent.Diazepam can be combined with xylazine-ketamine for better muscle relaxation.

3. Guaifenesin: It is a centrally acting skeletal muscle relaxant that produces mild sedation and analgesia. It is given intravenously at 5, 10, and 15% at 50-100 mg/kg BW. It should not be given as single anaesthetic as the analgesia is not adequate. It is combined with thiopental or with xylazine-ketamine.

4. Guaifenesin-thiopental: they may be given together intravenously (2-3g of thiopental in 1 lit of guaifenesin 5 to10%). Alternatively, induction is first achieved by Guaifenesin followed by thiopental (0.2-0.3%. 3-4mg/kg IV) or

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ketamine. Anaesthetics are repeated if longer duration is required. After single bolus, anaesthesia lasts for 15-25 min.

5. Guaifenesin- xylazine-ketamine: All the above drugs may be given together or separately xylazine (500 mg), ketamine (2000 mg) and guaifenesin (50 mg) are mixed in 1 lit solution and given at 1-2 ml/kg for induction and 2 ml/kg/hr for maintenance. Bradycardia and respiratory depression are major concern.

Inhalant anaesthesia in horses:

A specific large animal anaesthetic apparatus is required Inhalant method is preferred if surgery is longer than 45 min Halothane and isoflurane are commonly used inhalant anaesthetics. Recovery is faster with isoflurane than halothane Cardiovascular and respiratory depressions are present with both

anaesthetics. Induction should not be attempted with inhalant drugs in adult horses.

Unlike foals induction is achieved using thiopental or xylazine-ketamine.

Intraoperative monitoring in horses:

Physical methods of monitoring are usually adequate. Eye examination is important. In surgical plane, there is dull palpebral reflex, strong corneal reflex and slow nystagmus. Rapid nystagmus and blinking will indicate lighter anaesthesia. Blood pressure monitoring becomes important if anaesthesia and surgery exceeds 45 min.

Recovery: Horses need extreme care during recovery due to fractures and injuries during that period. Xylazine (0.2mg/kg) can be given to calm down the horse during recovery. Head rope and tail rope may be applied and tied to the rings in the recovery room.

Clinical protocol of anaesthesia in ruminants:

Ruminants accept physical restraint well and can be operated under sedation and local analgesia. General anaesthesia is used for thoracic surgery or for Diaphragmatic hernia.

Sedation: Xylazine is the most commonly used sedative in cattle (0.05-0.1mg/kg). Higher doses will lead to recumbancy and lighter general anaesthesia.Sheep and goats: require 0.1mg/kg BW of xylazine. Acepromazine is a commonly used phenothiazine derivative in cattle. However, it is not commonly used in cattle like horse’s, dose of 0.01-0.03mg/kg IM is sufficient. Sedation with acepromazine is associated with protrusion of penis and regurgitation if rumen is full.

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General anaesthesia: sedatives are not usually used before induction in cattle as they may prolong recovery. IV anaesthetics recommended for ruminants are thiamylal (6-10mg/kg), propofol (6mg/kg), guaifenesin. Propofol produces anaesthesia for 5-10 minutes, induction and recovery is smooth. Xylazine (0.05mg/kg) and ketamine (2mg/kg) can also be used.

Local analgesia: Most of the operations in ruminants are done under local analgesia with sedatives. Various local anaesthetic techniques such as linear infiltration, regional nerve blocks are used. Lignocaine hydrochloride is the most commonly used agent. The dose is 2mg/kg BW.

Anaesthetic protocols for caesarean

Dogs: Reduce dose of general anaesthetics to one third, Lumbosacral epidural analgesia. (Thiopental/propofol/ketamine)

Horse: General anaesthetics (reduced dose); thiopental + halothane

Ruminants:Local analgesia (sedative may be avoided),Reduce dose of analgesia

ConclusionsNecessity of anaesthetic combination and techniques are increasing

Not a single protocol is suitable for all species and for all surgeries Dogs and horses are operated under general anaesthesia Mostly cattle, sheep and goats are operated under local analgesia Success of general anaesthesia depends on type of species, weather canine,

equine, ruminant or wildlife.

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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.

Why 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:

What organ/s is/are involved?

What pathogen is most likely?

What antibiotic in most likely to be effective?

What drug concentrations at the site of infection?

What drug/route are most likely to achieve that concentration?

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ANTIMICROBIAL

PHARMACOKINETCS

Absorption Distribution Metabolism Excretion

Species Plasma protein binding Species Species

Dosage forms Physiological barrier Hepatic dysfunction Urinary pH

Pka/pH Dehydration Enterohepatic cycling Diuretics

Chemistry Blood buffer Nutrition Renal path.

Route of adm. Inflammation

First-pass-effect Pregnancy/Lactation

Neonates Drug interaction

Diet

Concomitant medication

G.I motility modifiers

Fig: Factors affecting antimicrobial concentration in blood/tissue & its action

Clinical Pharmacokinetics

Absorption: The absorption and disposition of antimicrobial agents in the body are largely 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 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.

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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 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.

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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

(Leukocyte, Macrophage)

Gentamicin,Polymyxin Pus

Aminoglycosides Decreased pH, anaerobiasis, hyperosmalarity

Cephalosporins:

Wide variation in pharmacokinetic properties is observed among cephalosporins. Generally cephalosporins possess widespread distribution in ECF in the body, but their penetration across biological membranes/barriers varies with the compound. Many cephalosporins (II & III generations) diffuse across biological membranes/barriers and attain high concentration in synovial fluid, occular fluid, prostate or CSF.

Group I (eg: cephalothin, cefaloridine) does not pass across blood : milk or blood : CSF barrier. However, Group II (eg: cefataxime, cefamandole) can pass across inflamed meningeal layers and therefore, drug of choice for meningitis caused by enterobacteriaceae. Group III (eg: cefoperazone) and Group IV (moxalactam) are highly active against P.aeruginosa. Third generation

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cephlosporins are also lipid soluble. Cefoperazone undergoes hepatic metabolism and disturb large bowel (horse) activity but it is suitable for intramammary administration (250 mg in oily base) in bovine mastitis. Its milk concentration exceeding MIC of common pathogens stays upto 48 h following single infusion.

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.

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

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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

-lactum (old) + III - Gen. of cephalosporins Depression of resistance enzymes

Trimethoprim + Sulfonamide Synergistic

Ampicillin + Cloxacillin Synergistic

Penicillin-G + Streptomycin Agonistic.

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 cure. To ensure this, the veterinarian must update their knowledge pertaing toclinical pharmacology of newer antimicrobials released in to market.

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POST-MORTEM EXAMINATION IN VETEROLEGAL POISONING CASE

B.KALA KUMAR

The veterinarian will be encountered with diagnosing and treating the animals exposed to toxicant /poison 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, 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.

Post-mortem examination 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,

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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.

Collection of samples A successful toxicological investigation requires appropriate specimens, history

and clinical signs, necropsy lesions and circumstantial evidences. 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 feedMost 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. In cases where the poison is suspected to be absorbed per-cutaneously or consumed by inhalation, appropriate tissue specimens (skin or lung, brain, heart) must be collected. In case of abortion following ingestion of poisonous material, uterus and fetus may also be helpful during investigation. If there is a strong suspicion of criminal poisoning or if litigation appears

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possible in accidental poisoning, specimens should be collected in duplicate and placed in sealed containers in the presence of witness. In such medico-legal cases, the veterinarian should record clinical, pathological and epidemiological findings in detail. Further photographing of the affected animals and the surrounding environment is also indicated for documentation, if required to be produced in the court. The skeleton or the remnant bones are the important material for analysis in cases of exhumed bodies while burnt bones and ashes should be preserved for analysis in cases cremated bodies.

Sampling containersSpecimens for toxicological examination must be collected preferably in wide

mouth glass bottles of about 2L capacity having air tight stoppers. Alternatively, plastic containers can be used in place of metallic containers or old cans to avoid contamination by lead or other metals. The sampling bottles should be numbered, labeled properly, indicating details of the case, nature of content, place and date of

preservation. Do not forget to put your signature (i.e. veterinarian who has conducted necropsy). Specimens should be packed individually and necessary measures should be taken to avoid loss of some poisons by escape of gas or by bacterial fermentation.

Preservation of materials 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.

Adequate refrigeration is of special importance when submitting body fluids and materials for nitrate/nitrite analysis

Preservation of blood samples can be done either by using sodium fluoride (20 mg/ml of blood) or mixture of sodium citrate and HgCl2 (10 g + 0.2g, dissolved in 100 ml of distilled water, add 0.5ml / 10 ml of blood).

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Packing 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.

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

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

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

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.

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

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

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

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

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

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

heat seal, screw caps must be reinforced with tape. In case of the samples being transported in refrigerated or frozen state using

ice pack/ waterproof frozen sachets, screw caps should not be used. Rumen contents/vomitus is preferred to be sent to establish that the toxin has

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

veterolegal cases

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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 .

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.

It is always preferable to send the specimens through a special messenger.

In veterolegal cases, the specimens should be sealed in the presence of a witness

A sample of the preservative used should be sent. It is always better to have a duplicate

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

Name and address of the doctor and the owner of the animal Animal identification characteristics-species, colour, age, sex, breed etc. Number of animals affected and number of animals dead Date of onset of symptoms and the death Clinical signs recorded by the doctor and symptoms noticed by the owner Type and the quantity of samples sending Postmortem findings Suspected poison/toxicant Any other circumstantial fact or information which may assist the laboratory in

identifying the causative agent

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

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Toxicological specimens for laboratory examination

Sl.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

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 100g Airtight containers

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sample,

Liver, Kidney, Brain.

100g

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

Organocarbamates

Feed

Ingesta

Liver

Urine

100g

100g

100g

50ml

--

12. Oxalates Fresh forage

Kidneys

100g

100g

Fixed in formalin

13. Sodium (NaCl) Brain

Serum

CSF

Feed

100g

5ml

1ml

1-2kg

--

14. Znic phosphide Liver, Kidney

Gastric contents

100g

100g

--

*****

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GENERAL LINE OF TREATMENT OF POISONING IN ANIMALSM.VIJAY KUMAR

For the majority of cases of poisoning 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.

Removal of the poison

1. 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 all be cleaned with the greatest care, paying particular attention to areas such as the ears, between toes, etc.

The cleaning should be undertaken quickly to avoid licking and ingestion of the poison, and to limit cutaneous absorption.

Use soapy water (preferably a soap with a low pH), rinsing with copious tap water; repeat as often as necessary

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 The animal could well be in a state of shock and must be handled accordingly. Move to a quiet place with additional heating (e.g. a heat pad, if necessary)

2. Gastric emptying:

a. 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

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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. Recommended emetics for use in dogs and cats (if necessary, in pigs):

Apomorphine for dogs: Prompt effect, thorough, but does have 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, for dogs and cats: 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 If none of the above compounds are available, possible alternatives include:

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)b. Gastric lavage:

Currently used in dogs. It is indicated:

If ingestion has taken place in the preceding 2-4 hours On anaesthetized animals with endotracheal intubation

Use 10 ml/kg of an isotonic solution of sodium chloride (occasionally sodium bicarbonate); repeat the procedure until the washout fluids is clear.

Manual gastric emptying is used in ruminants. Emergency gastrotomy with manual emptying may be necessary in some cases of plant poisoning or for indigestible materials (such as plastic, polyurethane foam).

2. Purgatives:

Never use irritant purgatives and Oil-based purgatives as they facilitate absorption

Recommended purgatives:

Sodium sulphate, magnesium sulphate, by mouth or 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

1. Diuretics:

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A. Increase glomerular filtration by instituting a forced diuresis or osmotic diuresis

5% glucose solution, by slow intravenous infusion:Large animals: 2-5 ml/kg per 24h, Small animals: 5-20 ml/kg per 24hr

10% glucose solution, by slow intravenous infusion: Large animals: 0.5-1 ml/kg per 24 h, Small animals: 1-2 ml/kg per 24 hr

10% mannitol solution, by intravenous infusion:Large animals: 1-2 ml/kg per 24 h, Small animals: 2 ml/kg per 24 hr

B. With diuretics (Note: strong diuretics are contraindicated):

Frusemide (im or iv), Large animals: 0.5-1 mg/kg, Small animals: 2.5-5 mg/kgC. Reduce 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 ivLarge animals: 7-10 g, Small animals: 0.1-0.2 g/kg

Ascorbic acid, iv, all species: 40 mg/kgForced 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 weight in (kg)

Ringer’s lactate, by iv infusion: all species: 5-10 ml/kg per hr Trometamol, 3.66% solution by iv infusion:

Dogs: 1-4 ml/kg per 24 hr

Use a diuretic such as acetazolamideDialysis:

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

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1. Adsorbents

Activated vegetable charcoal (fine medicinal charcoal or BCK granules). These are 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 gOther adsorbents: All other adsorbents are less effective than activated charcoal and are of academic interest only:

Magnesium oxide (magnesia), Kaolin, Universal antidote (vegetable charcoal 10g+ magnesia 5g + kaolin 5g + tannin 5g with water added up to 200 ml)2. 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.

Ferric hydrate (action as above).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”.

C. Additional treatment measures

These vary widely according to the symptoms observed, but one of the main preoccupations of the practitioner will be to support vital functions (respiration and circulation). The most frequently used agents are:

Doxapram: A respiratory stimulant, Dog/Cat: 2 mg/kg, iv, repeat as required Caffeine and theophylline: Cardiovascular and respiratory stimulants, which

also have a diuretic action. Dosage: 100-250 mg iv, im, hypodermally or as required

Nikethamide: A respiratory stimulant. Dog: 22-44 mg/kg, im, iv,

Heptaminol: A cardiac stimulant Rational Use of Charcoal

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Activated charcoal is useful in following circumstance. Charcoal is ineffective against cyanide. It can also adsorb vitamins/minerals and therefore continued use may prove to be harmful.

Aconite

Alcohol

Camphor

Cocaine

Digitalis

Glutethimide

Methylene blue

Copper sulphate

Antimony

Arsenic

Iodine

Oxalates

Selenium

Silver

Phosphorus

Stramonium

Antipyrene

Atropine

Barbiturates

Morphine

Mercuric chloride

Strychnine

Salicylates

Muscarine

Quinine

Parathion

Nicotine

Phenolpthaline

Phenothiazine

Sulfonamides

Penicillin

Ethylene glycol

Ipecacuana

Penicillin

Note: This is not an exhaustive list

Method of administration:

Make slurry of the activated charcoal using lukewarm water. The rate of 2-8 g/kg should be given in a concentration of 1g/5-10ml water. Administration can be done 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.

*****

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THERAPEUTIC MANAGEMENT OF CRITICALLY ILL PATIENTS

VIVEK .R. KASARALIKAR

Critically ill patient is a special challenge to the clinician because the underline problem is not evident for about 24 to 48 hrs 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.

Few important tips for first aid 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 should be controlled by digital pressure and pressure bandage

Penetrating foreign objects should be left in place till specialized help is available

Head should be elevated by 20o in altered mental status after head or spinal injury

Evaluation and initial treatment:

Triage is the art of assigning the priority to emergency patients and to their problems by evaluating certain parameters. Three important assessment criterion are A, B and C.

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

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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 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. It is clinically classified in to four main categories.

Hypovolemic shock: It occurs due to at least 15-25 percent deficit in circulatory blood volume

Cardiogenic shock: it occurs due to failure of heart to pump requisite quantity of blood in to circulation

Distributive shock: It is 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

Stage of apnea with cyanosis of visible mucous membranes

Absence of palpable pulse

Absence of heart sounds

Dilatation of pupils

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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:

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 determined. Crystalloid supplements fluid along with electrolytes, whereas colloidal solutions expand the plasma volume.

Commonly used colloidal solutions are

Dextran 70

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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

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 drugs decrease the prostaglandin synthesis and other vaso-active amines. 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.

*****

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TOXICOLOGY OF POISONINGS OF VETERINARY INTEREST AND THEIR CLINICAL MANAGEMENT

N.PRAKASH

Poisoning in most occasions is accidental in farm animals, but it may occasionally be deliberate or what we call ‘criminal poisoning’. In the veterinary field (farm animals) 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.

SOURCE OF POISONINGS

Agrochemicals (viz: insecticides, fungicides, herbicides, defoliants, rodenticides etc.), HCN containing fodder crops/plants/seeds, nitrate/nitrite rich plants or water source, industrial effluents, lead based paints, mycotoxins, water contaminated with blue-green algae and regional specific poisonous plants (also seasonal) are some of the common source of accidental poisonings in farm animals.

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, but their mechanism of action differs. Therefore, their chemical classification is helpful in early diagnosis of poisoning and to initiate suitable therapeutic measures in poisoned animals.

Insecticides can be classified in to following categories:

Chemical class Examples

Organochlorines: Aldrin, Endosulfan, Lindane, Dicofol etc.

Oraganophosphates: Acephate, Malathion, Parathion, Methyl parathion, Dimethoate, Phosphamidon,, Chlorpyriphos, Chlorfenvinphos, Monocrotophos etc.,

Carbamates: Carbaryl, Metacil, Dimetan, Pyramat etc.

Pyrethroids (Synthetic): Deltamethrin, Cypermethrin,Permethrin, Allerthrin etc.

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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 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.

Studies (experimental) have indicated that Type-I pyrethroids (allerthrin, permethrin,cismethrin etc.,) cause ‘T-syndrome’- characterized by tremors. On the other hand type-II pyrethroids cause burrowing behaviour, clonic seizures and profuse salivation.

2. Rodenticides:

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Commonly used among farming community to control animal pests like rats, mice and wild species. These include Warfarin and second generation warfarin like compounds, Zinc-and aluminum phosphide, ANTU, Flouroacetate and outdated methods like bait made up of Arsenicals or Strychnine (seed powder).

Anticoagulant rodenticides: These include warfarin (less used now a days) and second generation anticoagulant rodenticides viz: Bromadiolone (Mortin), brodifucoum. The main source of poisoning is the ingestion of residues of the rodenticides or baits intended for killing rodents. These rodenticides interferes with normal function of vitamin-K and causes coagulation defects by inhibiting clotting factors II,VII,IX and X. 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. Commonly used in fruit market, horticultural farming, and almost every grocery shops/ APMC yard to destroy rats, mice, squirrels etc. Often it is also used in malicious poisonings to kill dogs, cats and even wild animals. Monogastric species are more sensitive rather than ruminants. Acute zinc phosphide toxicities is due to conversion of Zinc-phosphide phosphine (PH3) gas in the stomach following hydrolytic reaction with water in the GIT under acidic pH. Absorption od phosphine is responsible for wide spread cellular toxicity with necrosis of GIT and other vital organs like liver and kidneys. 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.

3. Herbicides & Fungicides:

Dinitro-compounds: Dinitrophenol, DNP; dinitro-orthro cresol, DNOC); are some of the commonly used as herbicides. Accidental ingestion foliage sprayed with these

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compounds may lead to acute toxicity in ruminants. These compounds are reduced by ruminal microflora in to diamine metabolites which induce methaemoglobinemia. They uncouple oxidative phosphorylation and convert all the cellular energy in the form of heat. In ruminanats, but not in non-ruminants intravascular haemolysis is observed. Hyperthermia, dark coloured blood and gastroenteritis are observed in poisoned animals. Rapid onset of rigor mortis, yellowish-green coloured tissues/urine may be recorded during post mortem examination.

Organic mercurials: These compounds include ethyl mercuric chloride and –hydroxide, methyl mercuric dicyandiamide and methoxy ethyl mercuric silicate used as fungicides for seed dressing. Organic mercurials are neurotoxic unlike inorganic mercurials which are corrosive and nephrotoxic.

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 for m of HCN poisoning in livestock is caused by various cyanogeneetc plants capable of producing hydrocyanic acid. Such plants (see poisonous plants discussed below) 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.

The lethal effects of cyanide is due the its binding with Fe+3 component of cytochrome oxidase a3, a key enzyme involved in cellular respiration. Thus, 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 1-11/2 hours 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-

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mortem examination impart similar odour. Animals suspected for HCN poisoning must be differentiated from nitrite and other sr milar agents before initiating antidote therapy (see table 2). 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 (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.

Systemic antidotes-Dosage and method of treatment (Large Animals)

Poisoning Antidote/ treatment Dosage and method of treatment

Hydrocyanic acid/Cyanide

Sodium nitrite followed by Sodium thiosulfate

Administer 1% sodium nitrite @ 15-25mg/kg,i.v followed by 25% sodium thiosulphate @ 1.25g,i.v

In emergency:

Na nitrite + Na thiosulfate

Cattle: 20%, 10ml + 20% ,50 ml

Horse: 20%, 10ml +

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20%,50ml

Sheep: 10%,10ml + 10%,20ml

Administer 4L of vinegar in 10-20Lcold water; give a large dose of vitamin B12

Administer anticonvulsants if necessary

Nitrate/nitrite Methylene blue

or Ascorbic acid

1% methylene blue @ 8.8mg/kg, i.v

Administer 8-10L cold water and saline purgatives; Broad spectrum antibiotics intra-ruminally

Heavy metals

(Arsenic,antimony, mercury, etc.)

Arsenic poisoning

British anti-Lewisite(BAL)

or

d-penicillamine

(Expensive)

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 6 hr 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 requiredAdminister @ 30-40mg ,i..v + 60-80mg/kg ,p.o, b.i.d or t.i.d for 3-4 days

Urea Reduce the rumen pH Administer 20-30L cold water and drench 4-6L of 5 % acetic acid

Strychnine

(Strychnous- nux -vomica)

Phenobarbital sodium

or Chloral hydrate

@ 30mg/kg,i.v or

5g/45 kg body weight, i.v

Drench tannic acid and then cathartic

Anticonvulsants, Leave the animal in calm, noise free and dark room

Lead Calcium disodium EDTA

Make 6% solution and administer @ 73 mg/kg,i.v(repeat, if required). After two days gap start therapy

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again for next 5days

AnticonvulsantsCopper Ammonium tetra

molybdate

or Ammonium molybdate + Sodium thiosulphate

or

d-penicillamine

(Expensive)

1.7 mg/kg,i.v drip daily for 3-5 days.Allow 2days gap and then start therapy for next5days

Give ammonium molybdate 50-500mg p.o, s.i.d and sodium thiosulfate 300-1000mg,p.o,s.i.d for three weeks

Supportive treatment

26mg/kg,p.o,b.i.d for 6 days

Warfarine Vitamin K1 300-500mg,s.c,every 4-6hour

Blood transfusion and supportive care

Ethylene glycol Ethyl alcohol 20% ethanol @ 5ml/kg for every 4-8 hours interval

Carbamate insecticides

Atropine sulphate 0.25mg-0.5mg/kg,give ¼ intravenously and remaining ¾ by intramuscular or subcutaneous route

Organophosphates Atropine sulphate +

2-PAM

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

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-compounds (Herbicides like DNOC, dinitrophenol)

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 every 8hr. for first 24-48hr.

Do not give antipyretics to control hyperthermia. Use cold water or ice packs. Administer saline

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purgatives. Fluid therapy with dextrose saline

Systemic antidotes-Dosage and method of treatment (Small Animals)

Toxic agent Systemic antidote Dosage and method of treatment

Acetaminophen N-acetylcysteine 150 mg/kg loading dose PO or IV, then 50 mg/kg q 4h for 17-20 additional doses.

Arsenic, mercury and other heavy metals except cadmium, lead silver, selenium and thallium.

Dimercaprol (BAL)

[Knoll Pharma]

10% solution in oil:give small animals 2.5-5.0 mg/kg IM q6h for 2 days then q12h for the next 10 days or until recovery (Note: With severe acute poisoning, 5 mg/kg should be given only on the first day).

D-penicillamine (Artamin)® - VHB

(Cilamin)® - IVIL

Developed for chronic mercury poisoning and now seems most promising drug. No reports on dosage in animals but give 3-4 mg/kg q6h.

Atropine, belladonna alkaloids

Physostigmine salicylate 0.1-0.6 mg/kg (do not use neostigmine)

Barbiturates Doxapram

2% solution: give small animals 3-5 mg/kg, IV only (0.14-0.25 ml/kg). Repeat as necessary. (Note: The above is reliable only when depression is mild; in animals with deeper levels of depression ventilatory support (and oxygen) is preferable).

Cholinergic agents and cholinesterase inhibitors

Organophosphates, some Carbamates but not carbaryl, dimethan or carbam piloxime)

Pralidoxime chloride

(2-PAM)

5% solution 20-50 mg/kg IM or by slow IV (0.2-1.0 mg/kg) injection (maximum dose is 500 mg per minute). Repeat as needed. 2-PAM alleviates nicotinic effect and regenerates cholinesterase. Morphine, succinylcholine and phenothiazine tranquilizers are contraindicated.

Copper d-penicilamine (Artamin)

See arsenic

Coumarin- Vitamin K (K1) Give 3-5 mg/kg SC or PO per day

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derivative anticoagulants.

1% emulsion or capsule

with canned food. Treat 7 days for warfarin-type. Treat 21-30 days for second generation anticoagulant rodenticides, oral therapy is more effective than parenteral route

Fresh whole blood.

Fresh plasma or fresh frozen plasma

Blood transfusion 10-25 ml/kg; as required.

Edrophonium chloride

Ventilatory support

1% solution give 0.05-1.0 mg/kg IV.

Cyanide Methemoglobin (sodium nitrite is used to form methemoglobin) and

1% solution of sodium nitrite, dosage is 16 mg/kg IV (1.6 ml/kg)

Sodium thiosulfate Follow with 20% solution of sodium thiosulfate at dosage of 30-40 mg/kg (0.15-0.2 ml/kg) IV. If treatment is repeated, use only sodium thiosulfate (Note: both of the above may be given simultaneously as follows:- 0.5 ml/kg of combination consisting of 10g sodium nitrite and 15 g sodium thiosulfate in distrilled water QS. to 250 ml. Dosage may be repeated once and if further treatment is required give only 20% solution thiosulfate at 0.2 ml/kg.)

Digitalis glycosides Oleander and Bufo toads

Potassium chloride Dogs : 0.5-2.0 g PO in divided doses or in serious cases as diluted solution given IV by slow drip (ECG monitoring is essential)

Diphenylthydantoin

Propranolol (-Blocker)

Atropine sulfate

25 mg per minute IV, until ventricular arrhythmias are controlled.

0.5-1.0 mg/kg IV or IM. Give as needed to control cardiac arrhythmias (ECG monitoring is essential)

0.02-0.04 mg/kg as needed for cholinergic and arrhythmia control.

Fluoride Calcium borogluconate 3-10 ml of 5-10% solution.

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Pentobarbital May protect against lethal dose (experimental) (Note: all treatments are generally unrewarding).

Heparin Protamine sulfate 1% solution give 1.0-1.5 mg by slow IV injection to antagonize each 1 mg of heparin. Reduce dose as time increases between heparin injection and start of treatment (after 30 minutes give only 0.5 mg)

Iron salts (Iron tonics)

Deferoxamine mesylate (Desferal, Ciba)

Dosage for animals not yet established. Dosage for humans is 5 g of 5% solution PO, then 20 mg/kg IM q4h-q6h. In case of shock, the dosage is 40 mg/kg by IV drip over 4-hour period. May be repeated in 6 hours then 15 mg/kg by drip q8h.

Lead Calcium disodium EDTA (CaEDTA)

Maximum safe dosage is 75 mg/kg per 24 hours (only for severe case); EDTA is available in 20% solution for IV drip, dilute in 5% glucose to 0.5%; For IM, add procaine to 20% solution to give 0.5% concentration of procaine.

EDTA and BAL BAL is given as 10% solution in oil.

(a) In severe cases (CNS involvement with > 100 mg lead per 100 mg whole blood) give 4 mg/kg BAL only as initial dose: follow after 4 hours and q4h for 3-4 days with BAL and EDTA (12.5 mg/kg) at separate IM sites: skip 2 to 3 days and then treat again for 3-4 days:

(b) In subacute cases with < 100 g lead per 100 mg whole blood give only 50 mg EDTA/kg per 24 hours for 3-5 days:

Penicillamine (Cuprimine, Merck, Artamin® VHB)

(c) May use after either treatment (a) or (b) with 100 mg/kg per day PO for 1-4 weeks.

Thiamine hydrochloride Experimental to treat CNS signs: 5 mg/kg IV q12h for 1-2 weeks: give slowly and watch for untoward

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reactions.

Methanol Ethanol Give 1.1 g/kg (4.4 ml/kg) of 25% solution IV: then give 0.5 g/kg (2.0 ml/kg) q4h for 4 days. Prevent or correct acidosis with sodium bicarbonate 0.4 g/kg IV. Activated charcoal, 5 g/kg PO if within 4 hours of ingestion.

Oxalates Calcium 10% solution of calcium gluconate IV; give 3-20 ml (to control hypocalcemia)

Phenothiazine Methamphetamine hydrochloride

Diphenhydramine hydrochloride

0.1-0.2 mg/kg. Treatment for hypovolemic shock may be required.

For CNS depression, 2.5 mg/kg IV to treat extrapyramidal sings.

Strychnine and brucine (Nux-vomica)

Pentobarbital Give IV to effect: higher dose is usually required than that required for anesthesia. Place animal in warm and quiet room.

Amobarbital

Thiobarbiturates

Give slowly IV to effect: duration of sedation is usually 4-6 hours.

Dog/cat : 60-70 mg/kg IP.

Glyceryl guaiacolate

Diazepam (Valium®, Roche)

110 mg/kg IV 5% solution; repeat as necessary

2.5 mg/kg; controls convulsions

Prussian blue 0.2 mg/kg PO in 3 divided doses daily.

Potassium chloride Give simultaneously with thiocarbazone or Prussian blue; 2-6 g PO daily in divided doses.

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MYCO AND ZOO TOXINS OF VETERINARY IMPORTANCE: MANAGERIAL METHODS

M.VIJAY KUMAR

Mycotoxins are defined as 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. A few principles characterize mycotoxic diseases:

1) The cause may not be immediately identified

2) They are not transmissible from one animal to another

3) Treatment with drugs or antibiotics has little effect on the course of the disease

4) Outbreaks are usually seasonal because particular climatic sequences may favor fungal growth and toxin production

5) Study indicates specific association with a particular feed

There are various types of mycotoxins and are classified as follows:

Classification:

i)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.

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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) for the fear of M1 metabolite. In India the practicable limit is up to 50 ppb (0.05ppm) that can be fed to beef cattle, poultry and swine.

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: i)Acute - sudden death or anorexia, depression, dyspnoea, coughing, nasal discharge, anaemia, epistaxis, bloody faeces, possible convulsions and death.

ii)Sub- acute - jaundice, hypoprothrombinemia, haematomas and haemorrhagic enteritis.

iii)Chronic - decreased feed efficiency, decreased productivity and weight gain, rough hair coat, anaemia, enlarged abdomen, mild jaundice, depression and anorexia. Abortions may occur.

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

Microscopically

Typical hyperplasia of bile duct,Neoplastic growth of hepatocytes,Hyperchromasia

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

Differentiate diagnosis:

Warfarin (haemorrhages), coal tar (mottling of liver) Copper poisoning (haemoglobinuria, hemolysis); Pyrrozolidine alkaloids (present in plants), CCl4, blue-green algae, crotalaria are hepatotoxic. Rx: -

1. Avoidance of contaminated feed

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2. Hydrated sodium calcium alumino silicate (HSCAS) adsorb aflatoxins @5kg /ton

3. Stanozolol (2 mg / kg) I/M decreases hepatic necrosis4. 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, PH7 Phosphate buffer**Along with charcoal,stanzolol/oxytetracycline(any one)

6. GSH Precursors Cysteine,methionine @2.2mg/kgi/p7. Multi vitamins Like E,K & Selenium8. Treatment of grains with anhydrous NH3,H2o2,Chlorine,O3 but efficacy not

been established9. Feeding easily digestible and low fat diet containing adequate protein

Sample collection :

Much of the error in detecting mycotoxins in feed results from sampling (or subsampling) rather than from analytical methodology. Samples can be taken at various stages—from 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). Sampling is 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.

Probe sampling is acceptable when grain has been recently blended but is less reliable because different microenvironments within the storage facility may cause areas of mold or mycotoxin concentration. 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,

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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.

Zootoxins- care and management of envenomed patients:

There are about 236 species of snakes in India but only 50 of these are venomous, However, the common poisonous snakes of India that man and animal come into contact, which are those we call the ‘Beg Four’: 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. However, Occurrence of venomous bite from these snakes are less common. 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.

Table 1: Nature of toxicity of poisonous snakesFamily Elapidae Viparidae Crotalidae

Poisonous snakes Cobra King Cobra Krait

Russel viper * Pit Viper

Toxic Nature Neurotioxic Haemotoxic Neutrotoxic Haemotoxic

Table 2: Venom discharge and lethal dose of various snake venom

Snakes Discharge/bite (approx) Lethal dose

Cobra 200 mg 12-15 mg

Krait 20 mg 6-8 mg

Russel viper 150 mg 15-18 mg

Echis 3.8 mg 8-10 mg

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All the bites from venomous snakes do not lead to death due to “dry bites” which means that no venom was injected. But, since some snake venoms (like that of the krait) do not have immediate effect even in a bad bite, it is wise to give veterinary/medical care.

Cobra: Cobras are widespread group of snakes. In India, we have three kinds: the monocled, spectacled and black. Cobras can be easily identified by their “defence display” by spreading their long bones to their famous hood. Cobras 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. They lay eggs (10-30) between June & August and female stays with them until they hatch two months later. The cobra venom is rich in 10 or more macromolecular substances. These includes 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 is easy to recognise. It 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. The krait is often confused with smaller harmless wolf-snake.

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. They give birth to youngones directly, usually 20-40 at a time and equipped-with venom and fangs birth, viper venom is rich in proteolytic enzymes, hemolytic and spreading factors.

Saw scaled viper: It is the smallest member of “big four” and usually confused with long and thinner cat snake. In South India it grows to only 30 cm. length and it is the causes of many bites as it is widely distributed. The body has brownish and white zig-zag pattern and the head, as in all vipes, is flat, Usually they hide under rocks and bouldersor/in low shrub bushes.Like kraits, saw scaled vipers are noctoral but

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sometime can be seen in sun after a wet night. They have living young. usually 4-8 at a time, which are just 8 cm. at birth.

Pit vipers:These 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. There are 15 species of pit vipers and bites are fairly common. Venon is not powerful and seldom results in death. Young pit vipers aften lift their “colourful tail” to attract frogs.

First-Aid treatment:

The first and foremost aim, in case of cobra/krait bite is to retard the absorption of venon from the site of bite. This can be 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). In such case, freezing of tissue is ideal to reduce enzyme activity.

Hospital treatment:

The nature of hospital treatment practically depends on identity of the poisonous snake. Polyvalent antivenin (Haffkine Institute, Mumbai) is the drug of choce in the absence of identity. It is better to avoid administration of anti-histaminic as they are found to increase toxic potential of certain viper’s venom. Popularly, hopital treatment can be remembered as “AAA”:

A = Antivenin.

A = Antibiotic (broad spectrum)

A = 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.

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

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