AFRICAN COLLEGE OF HEALTH (ACH)BNS YEAR 2 SEMESTER 2; WEEK 5 NOTES:

MONDAY: Adult Health (pg.2)

TUESDAY: Pharmacology (pg.10)

WEDNESDAY: Adult Health (pg.17)

THURSDAY: Pharmacology (pg.24)

FRIDAY: Adult Health (pg.31)

QUESTIONS? Email: africancollegeofht@nokiamail.com

ADULT HEALTH (MONDAY)

Typhoid (Enteric) Fever:

Definition: Typhoid fever is a systemic infection characterized by fever and abdominal pain caused by dissemination of Salmonella typhi and occasionally by S. paratyphi A and B and S.typhimarium, all of which are non capsulated, gram negative motile bacteria.

Epidemiology:

• Human beings are the only hosts for S. typhi and S.paratyphi. Thus enteric fever is transmitted only thorough close contact with acutely infected individuals or chronic carriers through ingestion of contaminated food or water.

• Chronic carriers are the source of infection harboring the organisms in their gall bladder (especially in the presence of gall stones) and rarely at other sites. It affects people of all ages and both sexes. Enteric fever is endemic in most developing countries.

• Currently the disease is observed at a great frequency in AIDS patients than the general population.

Pathogenesis:

Following ingestion of the organism in contaminated food or drink, Salmonella typhi passes the gastric barrier and reach the upper small intestine where the bacilli invade the intestinal epithelium and they are engulfed by phagosome which reside in the Peyer’s patches. The bacilli multiply and enter the blood

stream and cause transient bacteremia. At this stage the Salmonellae disseminate throughout the body in macrophages via lymphatic and colonize reticuloendothelial tissue (liver, spleen, lymph nodes, and bone marrow).

Patients have relatively fewer or no signs and symptoms during this initial incubation period. Signs and symptoms, including fever and abdominal pain result when a critical number of bacteria have replicated. During weeks after initial colonization, further inflammation of the Peyer’s patches may result enlargement and necrosis which may result intestinal hemorrhage and perforation. Infection may become persistent and invade the gall bladder. The clinical phase of the disease depends on host defense and bacterial multiplication.

Clinical Manifestation:

The incubation period varies from 3-60 days. The manifestation is dependent on inoculums size, state of host defense and the duration of the disease. The Severity of the illness may range from mild, brief illness to acute, severe disease with central nervous system involvement and death.

First week;

• Fever is high grade, with a daily increase in a step-ladder pattern for the 1st one week and then becomes persistent.

• Headache , malaise , Abdominal pain

• Initially diarrhea or loss stole followed by constipation in adults, diarrhea is dominate feature in children

• Relative bradycardia

• Splenomegally /Hepatomegaly

• “Rose spots” not commonly seen in black patients. In whites it appears as small, pale red, blanching macules commonly over chest & abdomen, lasting for 2-3 days.

• Epistaxis

Second week;

• Fever becomes continuous

• The patient becomes very ill and withdrawn confused, delirious and sometimes may be even comatose.

Third Week;

• The patient goes to a pattern of “typhoidal state" characterized by extreme toxemia, disorientation, and “pea-soup” diarrhea and sometimes may be complicated by intestinal perforation and hemorrhage.

Fourth Week;

• Fever starts to decrease and the patient may deferveresce with resolution of symptoms. At this point patient may lose weight.

• Relapse may occur in 10% of cases.

Complications of Typhoid fever:

• Gastrointestinal perforation and hemorrhage: are late complications that may occur in the 3rd or 4th week. May develop despite clinical improvement. These complications are life threatening and need immediate medical and surgical interventions.

• Other Less common complications;

Hepatitis,Meningitis,Arthritis,Osteomyelitis,Parotitis,Orchitis,Nephritis,Myocarditis,Bronchitis and Pneumonia.

N.B these complications can be prevented by prompt diagnosis and treatment

Chronic Carriers:

• Approximately 1- 5 % of patient with Enteric fever become asymptomatic chronic carriers

• They shed S.typhi in either urine or stool for > 1 year

• Incidence of Chronic carriage is high in women and among patients with biliary abnormality (e.g. gall stone, carcinoma of gall bladder) and other GI malignancies.

Diagnosis:

Can be suggested by the presence of Persistent fever and Relative bradycardia, which was found to occur in 86% of Africans. Rose spots, which occurs in 70% of whites and 20% of Africans.

Leucopenia; But definitive diagnosis of the disease requires laboratory tests;

1. Isolation of the organism by blood, stool or urine culture is diagnostic.

o The yield of recovery of the organism differs depending on the specimen cultured and the duration of clinical disease;

o Blood culture -mostly (up to 90%) patients have positive culture in the 1st week, and only 50% by the 3rd week. The yield is much lower if patient has taken antibiotics prior to the test.

o Stool culture is negative in the first week and becomes positive in 75% of patients in the 3rd week. Urine culture parallels stool culture. Widal test for O and H antigens

• The O (somatic) antigen shows active infection whereas the H (flagella) antigen could be indicative of past infection or immunization for typhoid.

• Widal test has certain limitations, and to make a diagnosis of current infection a 4X (fold) rise in titer on paired sera taken during the acute and convalescence phases is necessary.

Limitations of Widal test;

• It is non-specific and a positive test could be due to Infection by other salmonellae (as the antigen used for the test is also shared by other salmonellae) Recent vaccination for typhoid . Past typhoid (already treated)

• The demonstration of 4- fold rise in titer on paired sera is not useful for the treatment of acute cases, as this requires waiting for the convalescence phase of the disease and at this stage if the patient is lucky recovery will occur.

Treatment:

Antibiotic therapy is curative. These drugs can be given either orally or intravenous, depending on patient condition (able to take orally or not), severity of the disease. One should note that fever may persist for 4-6 days despite effective antibiotic treatment .

Oral drugs:

First Line;

Nowadays 4-amino quinolones are the drugs of choice because of their effectiveness on multidrug resistant typhoid, and low relapse and carrier rates. Ciprofloxacin, norfloxacin, ofloxacin, and pefloxacin are all equally effective.

• Ciprofloxacin: 500mg PO BID for 10 days

• Ceftriaxone 1-2 gm IM or IV for 10 -14 days 4- amino quinolones are not recommended for use in children and pregnant women because of their observed potential

damaging effect on cartilage of the growing animals. However, in severe infections especially by MDR strains, we have to outweigh the benefits and the potential risks.

Alternatives;

• Azithromycin 1 gm PO daily for 5 days

• Chloramphenicol 500 mg Po QID for 14 days

• Norfloxacin 400mg twice daily for 10 days. Chloramphenicol is very cheap and also quite effective with initial doses of 3 - 4 g/d for adults, with clinical response observed in 24 - 48hrs after initiation. Dose should be reduced to 2g/d when fever starts to decrease (usually after 5 - 6 days), and continued to complete 2 weeks treatment.

Intravenous drugs are recommended for critically sick patients who are admitted or for patients who are unable to take oral drugs;

• Ceftriaxone 2-4gm once a day for 3 days and then 1- 2gm IV/IM for a total of 10- 14 days.

• Intravenous Chloramphenicol 1gm IV QID for 2-3 days and then start PO medication as soon as the patient can take oral medication. This is a drug of choice for patients that need parenteral therapy.

Problems of antibiotic treatment:

• Multidrug resistant (MDR) S.typhi is reported in different parts of the world, especially Indian

subcontinent and Southeast Asia. Hence if resistance is suspected in an area, the preferred treatment would be with quinolones, azithromycin or third generation cephalosporins

• Early use of antibiotics is associated with high rate of relapse (up to 20%) as compared to untreated cases (where the relapse rate is 5 - 10%). This is due to inhibition of adequate development of immune response by early therapy.

• Eradication of chronic carrier state requires prolonged treatment with Ciprofloxacin for 4 weeks is effective and much better than the other drugs. Ampicillin or Amoxicillin 100mg/kg/d taken with Probenecid 30mg/kg/day for 6 weeks. Co-trimoxazole (160/800mg twice a day) plus Rifampicin 600mg orally/d for 6 weeks.

N.B. Drug treatment does not eradicate infection in 40% of the chronic carriers. Hence surgical resection of the gall bladder may sometimes be necessary.

Prevention and control:

• Improve environmental sanitation

• Identification and treatment of Chronic carriers

• Avoid food handling by chronic carriers

• Vaccination for travelers to endemic areas;

o Live oral vaccine (TY21a) 3 doses can be given to those over 6 years. Protective for several years

o Purified Vi polysaccharide vaccine given in a single dose to those over 2 years and HIV positives, is as effective as live vaccine.

PHARMACOLOGY (TUESDAY)

Cell membrane phospholipids:

Arachidonic acid 5-Lipooxygenase LeukotrienesPharmacological Actions: a. Smooth muscle: most stimulate myometrium and are known to be important in the initiation and maintenance of labor.Prostaglandin E has bronchodilator action. b. GIT: they increase intestinal motility. PG E inhibits gastric acid secretion and has cytoprotective action on the gastroduodenal mucosa. Both PG E and F produce contraction of the longitudinal muscle of the gut. They also stimulate intestinal fluid secretion, resulting in diarrhea. c. CVS: PGE is peripheral vasodilator and powerful natriuretic. PGF constricts arterioles and veins. d. Platelets: Thromobxane causes platelet aggregation and vasoconstriction. PG I (prostacycline) is found in the vascular endothelium and is a potent inhibitor of platelet aggregation and is a vasodilator. e. Miscellaneous: Prostaglandins are important in pain generation and perception. PGE and PGI produce hyperalgesia associated with inflammation.

Therapeutic uses; include cervical ripening and labor induction, control of postpartum hemorrhage, induction of abortion, and prophylaxis of NSAID-induced peptic ulcers.

Adverse Effects; include fever, diarrhea, abdominal cramps, headache, nausea, and vomiting.

DRUGS ACTING ON THE RESPIRATORY SYSTEM

1.1 Bronchial asthmaAsthma is physiologically characterized by increased responsiveness of the trachea and bronchi to various stimuli and by wide spread narrowing of the airways that changes in severity either spontaneously or as a result of therapy Impairment of airflow in bronchial asthma is caused by three bronchial abnormalities. i. Contraction of airway smooth muscles ii. Thickening of bronchial mucosa from edema and

cellular infiltration iii. Inspissations in the airway lumen of abnormally thick, viscid plugs of excessive mucus.

PHARMACOTHERAPY OF BRONCHIAL ASTHMADrug used in the treatment of bronchial asthma can be grouped into three main categories: 1. Bronchodilators a. Adrenergic agonists which include: Non selective agonists e.g. adrenaline, Selective agonists e.g. salbutamol b. Methylxanthines; theophylline derivatives c. Muscranic receptor antagonists e.g. Ipratropium bromide

2.Mast cell stabilizers, e.g. cromolyn sodium, nedocromil, ketotifen 3.Antinflammatory agents: corticosteroids

1.ADRENERGIC AGONISTS (SYMPATHOMIMETIC AGENTS)(a) Non- selective agonists - Epinephrine, ephedrine, isoprotenerol (b). Selective agonists - Salbutamol, terbutaline, metaproterenol, salmeterol, formaterol and etc

Mechanism of Action:?Agonists stimulate adenyl cyclase and increase formation of cAMP in the airway tissues. They have got several pharmacological actions important in the treatment of asthma. Relax smooth muscles. Inhibit release of inflammatory mediator or broncho constricting substances from mast cells. Inhibit microvasculature leakage Increase mucociliary transport

a. Non-selective ?agonists: Cause more cardiac stimulation,they should be reserved for special situation.

Epinephrine: very effective, rapidly acting

bronchodilator especially preferable for the relief of acute attack of bronchial asthma. Administered by inhalation or subcutaneously.

Side effects; include arrhythmia and worsening of angina pectoris, increase blood pressure, tremors etc

Contraindication: - hypertension, arrhythmia,

Ephedrine: compared to epinephrine, it has longer duration of action but more pronounced central effect and lower potency. It can be given orally. The drug is currently infrequently used because of development of more efficacious and beta2-selective agents.

b. Selective agonists:Largely replaced non selective agonists, are effective after inhaled or oral administration and have got longer duration of action. They are the most widely used sympathomimetics. Commonly used drugs both by oral and inhalation are Salbutamol, terbutaline, metaproterenol, pirbuterol and bitolterol. Salmeterol and formeterol are new generation, long acting selective agonists (with duration of action 12 hrs or more). These drugs appear to interact with inhaled corticosteroids to improve asthma control. Delivery of adrenoreceptor agonists through inhalation results in the greatest local effect on airway smooth muscle with least systemic toxicity.

Side effects: Tremors, anxiety, insomnia, tachycardia, headache, hypertension and etc.

Contraindications: Sympathomimetics are contraindicated in patients with known hypersensitivity to the drugs.

Precautions: They should be used cautiously in patients with hypertension, cardiac dysfunction, hyperthyroidism, glaucoma, diabetes, pregnancy.

2. METHYLXANTHINESThe three important methylxanthines are theophylline, theobromine, and caffeine. The theophylline preparations most commonly used for therapeutic purposes is aminophylline (theophylline plus diethylamine).

Mechanism of Actioni. Competitively inhibit phosphodiesterase (PDE) enzyme leading to increased cAMP level.ii. They competitively inhibit the action of adenosine on adenosine (A1 and A2) receptors (adenosine has been shown to cause contraction of isolated airway smooth muscle and to provoke histamine release from airway mast cells. iii. Inhibit the release of histamines and leukotriens from the mast cells Of the three natural xanthines, agents theophylline is most selective in its smooth muscle effect, while caffeine has the most marked central effect.

PharmacokineticsOnly slightly soluble in water so has been administered as several salts containing varying amounts of theophylline base. Most preparations are well absorbed from gastro intestinal tract and metabolized by liver. Doses should be decreased in cases of liver disease and heart failure.

Adverse Effects: Anorexia, nausea vomiting, abdominal discomfort, headache, anxiety, insomnia, seizures, arrhythmias.

Theophylline is now largely reserved for patients in whom symptoms remain poorly controlled despite the combination of regular treatment with an inhaled anti- inflammatory agent and as needed use of a agonist.

3. MUSCRANIC RECEPTOR ANTAGONISTSMechanism of Action: Muscarinic antagonist

competitively inhibit effect of acetylcholine at muscarinic receptors, hence block the contraction of air way smooth muscle and the increase in secretion of mucus that occurs in response to vagal activity e.g atropine sulfate Systemic adverse effects as a result of rapid absorption include urinary retention, tachycardia, loss of accommodation and agitation and local effects like excessive dryness of mouth limits the quantity of atropine used.

Ipratropium bromide is poorly absorbed and does not readily enter the central nervous system thus permits the delivery of high doses to muscarinic receptor in the airways; hence, it can safely be used for bronchial asthma. Antimuscranic antagonist drugs appear to be slightly less effective than agonists agents in reversing asthmatic bronchospasm, The addition of ipratropium enhances the bronchodilation produced by nebulized albuterol in acute severe asthma. The antimuscarinic agents appear to be of significant value in chronic obstructive pulmonary diseases - perhaps more than asthma. They are useful as alternative therapies for patients intolerant of agonists

4. ANTI-INFLAMMATORY AGENTS: CORTICOSTEROIDSUsed both for treatment and prophylactic purposes: Mechanism of action; They are presumed to act by their broad anti-inflammatory efficacy mediated in part by inhibition of production of inflammatory mediators. They also potentiate the effects of ?receptor agonists and inhibit the lymphocytic-eosinophilic airway mucosal inflammation Effects on airway decreases bronchial reactivity increases airway caliber decreases frequency of asthma exacerbation and severity of symptoms

The corticosteroids commonly used are hydrocortisone, predinisolone, beclomethasone, triamcinolone and etc.

The drugs can be taken by inhalation as aerosol, oral,

or an IV administration.Because of severe adverse effects when given chronically, oral and parenteral corticosteroids are reserved for patient who need urgent treatment and those who have not improved with

Bronchodilator:Aerosol treatment is the most effective way to decrease the systemic adverse effect of corticosteroid therapy. Abrupt discontinuation should be discouraged because of the fear of adrenal insufficiency. Doses should be decreased after improvement. Regular or controlled therapy is better maintained with aerosol corticosteroids.

Clinical uses in bronchial asthma: Urgent treatment of severe asthma not improved with bronchodilator;IV, inhalation or oral.

Side effects: Suppression of the hypothalamic-pituitary-adrenal axis . Sodium retention and hypertension. Cataract. Impairment of growth in children Susceptibility to infection like oral candidiasis and tuberculosis.

5. MAST CELL STABILIZERSe.g cromolyn sodium. Mechanism of action: Stabilize the mast cells so that release of histamine and other mediators is inhibited through alteration in the function of delayed chloride channel in cell membrane. It has no role once mediator is released and is used for casual prophylaxis.

Clinical uses; Exercise and antigen induced asthma.

Side effects; Poorly absorbed so minimal side effect.Throat irritation, cough, dryness of mouth, chest tightness and wheezing.ADULT HEALTH (WEDNESDAY)

Relapsing Fever:

Definition: Relapsing fever is an acute febrile illness caused by Borrelia species, presenting with recurrence of characteristic febrile periods lasting for days alternating with afebrile periods.

Relapsing fever describes two distinct diseases:

• Louse borne (Endemic) relapsing fever (LBRF):- transmitted by body louse Pediculus humanis var corporis

• Tick borne (Epidemic) relapsing fever (TBRF)- transmitted by tick (Ornithodoros)

Etiology:

Relapsing fever is caused by Borrelia species, which are spirochetal gram negative helical bacteria.

• B. recurrentis is the only species that cause LBRF

• B. duttoni is the commonest causes of TBRF in sub-Saharan Africa. Borrelia demonstrates remarkable antigenic variation and strain heterogeneity which help the parasite to escape the immune response of the host and result in recurrence of febrile episodes.

Transmission:

LBRF: Body lice become infected by B. recurrentis while feeding on spirochetemic human blood, the only reservoir of infection. Humans acquire infection when infected body lice are crushed and their fluids contaminate mucous membrane or breaks in the skin (such as abrasions caused by scratching of pruritic louse

bites).LBRF is now an important disease. Some of the risk factors for LBRF are overcrowding like in military camps, civilian population disrupted by war and other disasters.

TBRF: Rodents are the primary hosts and vector ticks become infected when they feed spirochetemic rodents. Ticks transmit the Borrelia vertically over several generations. TBRF is most highly endemic in sub-Saharan Africa but also is found in Mediterranean and Middle eastern countries.

Pathophysiology:

In humans, Borrelia after entering the body multiply in the blood and circulate in great number during febrile periods. They are also found in the spleen, liver, central nervous system, bone marrow, and may be sequestered in these organs during periods of remission. Severity is related to spirochetal density in blood but systemic manifestations are related to release of various cytokines.

The disease is characterized by sub capsular and parenchymal hemorrhage with infarcts of spleen, liver, heart and brain is seen. Thus, patients will have enlarged spleen and liver with variable edema and swelling of brain, lung and kidneys. Relapsing fever in pregnancy can result abortion, still birth and fatal neonatal infection Death from TBRF is rare. In contrast fatality rate of LBRF may reach up to 20 % during out

beaks mainly among malnourished and stressed population.

Clinical Features:

• The manifestation of both LBRF and TBRF are similar.

• Incubation period is 7 days (ranging from 2-18 days).

• The onset is sudden with high grade irregular fever, headache, chills, myalgias, arthralgias, and insomnia.

• Patient will be withdrawn, disinterested to food and other stimuli and thirsty. Patient will have delirium associated with high grade fever, tachycardia and dry tongue, injected conjunctiva and photophobia

• Summation gallop , occasionally resulting from myocardial involvement

• Upper abdominal tenderness with hepatosplenomegally,

• Scattered petechiae over the trunk, extremities and mucous membrane in 1/3 LBRF and fewer TBRF

• Symptoms and signs of meningeal irritation may be seen in some patients.

• Icteric sclera may be found in late stage of the disease.

Complications:-

Life threatening complications are unusual in otherwise healthy persons if the disease is diagnosed and treated early. Complications are common in late disease in untreated patients. Epistaxis, blood streaked sputum other bleeding tendencies Neurologic manifestations

like iridocyclitis, meningitis, coma, isolated cranial nerve palsies, Pneumonitis, Myocarditis and Splenic rupture etc. Without treatment, symptoms intensify over 2-7 days period and subside with spontaneous crisis during which Borrelia disappear from the circulation. Such cycles of febrile periods alternating with afebrile periods may recur several times.

Basic characteristics of the two types of Borrelia:

LBRF TBRFCauses B. recurrentis B. duttoni + many

others(all zoonotic)Parasite in the vector

Found in endolymph of lice

Found in all tissues, including salivary glands & ovaries

Transmission Contamination of mucous membrane or breaks or abrasions on the skin by body fluids of lice, released during crushing - Not transmitted by the bite of lice or inoculation of louse feces

By bite of tick during blood meal (organisms in the saliva & coaxal fluid of Borrelia)

Vertical transmission (Trans-Ovarian)

No Yes

Distribution East Africa Sub-Saharan Africa, Mediterranean littoral, middle east,

Russia, India, China, USA

Occurrence Epidemics are frequent in homeless people living in unhygienic crowded condition

Sporadic or in small often familial clusters

Vector longevity

Short life span Lives over 10 Yrs

Jarisch – Herxheimer Reaction

More severe Less severe

Eradication Easy Difficult because of: - the night biting habit & painless nature of the bite of ticks - vertical transmission/trans-ovarian/ - long life span.

Diagnosis:

• Diagnosis of relapsing fever is made based on demonstration of the organisms in blood, bone marrow, CSF etc Blood Film:

• Giemsa or Wright stained peripheral blood smear is an ideal test in the resource limited setting.

• Spiral organisms can be demonstrated on peripheral blood taken during febrile period preceding the crisis. This is positive in more than 70% of LBRF and in lower percentage of patients with TBRF.

Other Tests:

• Dark field microscopy of unstained blood/CSF

• Serologic tests.

Treatment:

Relapsing fever is treated with antibiotics. In LBRF single dose of erythromycin, tetracycline, doxycycline or chloramphenicol, produces rapid clearance of Borrelia from the blood & remission of symptoms. TBRF is less sensitive to these antibiotics and requires a 7 days course of treatment.

Adult Dosage:

Medication (Oral) LBRF (single dose)

TBRF (7 days schedule)

Erythromycin 500mg 500mg every 6 hrsTetracycline 500mg 500mg every 6 hrsDoxycycline 100mg 100mg every 12

hrs

Chloramphenicol 500mg 500mg every 6 hrs Parenteral: Penicillin G (procaine)

600,000 I.M stat

600,000 IM daily

Jarisch- Herxheimer Reaction (JHR):

• Rapidly acting antibiotics regularly precipitate JHR within 1- 4 hrs of 1st dose

• More sever in patients with LBRF than TBRF

• It is more sever when high numbers of spirochetes are circulating in the blood

• Jarisch- Herxheimer Reaction has three phases;

Chill phase:- lasts for 10- 30 minutes;

• Rigor, hyperventilation, high cardiac output,

• High body Temperature ( > or = 41 Co) accompanied by , agitation , confusion .

Flush phase:

• Fall in body temperature, drenching sweating, Potential dangerous fall in Systemic blood pressure ( as peripheral vascular resistance falls )

• Clinical and ECG evidence of myocarditis may be seen , S3 gallop and prolonged QT interval

• Vital signs must be monitored closely during this time which usually lasts for <or = 8 hrs.

Recovery (Deferverescence) phase:

• Vital signs slowly come to normal

• The Patients is exhausted .

Treatment of JHR:

• Close monitoring of vital signs

• Care full fluid management

• Control high body Temperature

• Short term digoxin I.V administration in patients with evidence of myocardial dysfunction.

Prevention and Control of Relapsing Fever:

• Avoiding over crowding

• Apply hygienic practices that reduce the number of body lice (washing clothes)

• Elimination of ticks

• Health education

• Early case detection and treatment of infected persons and close contacts

• In out breaks of LBRF, empirical single dose treatment with doxycycline

• Eradication of Rodents to control TBRF: ( Rodenticides ) .

PHARMACOLOGY (THURSDAY)

ANTI-TUSSIVES Cough is a protective reflex, which serves the purpose of expelling sputum and other irritant materials from the respiratory airway.

Anti-tussives are drugs used to suppress the intensity and frequency of coughing.

Two Types of Anti-tussives: 1. Central anti- tussives Suppress the medullay cough center and may be divided into two groups: Opoid antitussive e.g. codeine, hydrocodeine, etc Non opoid antitussives e.g. dextromethorphan

2. Peripheral antitussives: Decrease the input of stimuli from the cough receptor in the respiratory passage. e.g: Demulcents e.g. liquorices lozenges, honey

DEXTROMETROPHAN Dextromethorphan is an opoid synthetic antitussive, essentially free of analgesic and addictive properties and the main side effects are respiratory depression.

Expectorants are drugs that removes thick tenacious mucus from respiratory passages, e.g. Ipecac alkaloid, sodium citrate, saline expectorant, guanfenesin, potassium salts Mucolytics are agents that liquefy mucus and facilitate expectoration, e.g.acetylcysteine.

DECONGESTANTSDecongestants are the drugs that reduce congestion of nasal passages, which in turn open clogged nasal passages and enhances drainages of the sinuses.

Clinical uses: Used in congestion associated with rhinitis, hay fever, allergic rhinitis and to a lesser extent common cold. Drugs can be administered nasally or orally for longer duration of action.

Classification:1. Short acting decongestants administered topically; phenylepherne and phenylpropanolamine 2. Long acting decongestants administered

orally;ephedrine, pseudoephedrine and naphazoline 3. Long acting topical decongestants;Xylometazoline and oxymetazoline

Side effects: 1. Rebound nasal congestion 2. Ischemic changes in mucus membranes 3. Nasal burning, stinging, dryness 4. Tachycardia, arrhythmia, nervousness, restlessness, insomnia, blurred vision

Contraindications : Hypertension and severe coronary artery disease

DRUGS USED IN GASTROINTESTINAL DISEASESI. Drugs used in Acid-peptic disease:Acid-peptic disease includes peptic ulcer (gastric and duodenal), gastroesophageal reflux and Zollinger Ellison syndrome. Peptic ulcer disease is thought to result from an imbalance between cell destructive effects of hydrochloric acid and pepsin and cell-protective effects of mucus and bicarbonate on the other side. Pepsin is a proteolyic enzyme activated in gastric acid, also can digest the stomach wall. A bacterium, Helicobacter pylori is now accepted to be involved in the pathogenesis of ulcer. In gastroesophageal reflux, acidic stomach contents enter into the esophagus causing a burning sensation in the region of the heart; hence the common name heartburn, or other names such as indigestion, dyspepsia, pyrosis, etc.

Zollinger-Ellison syndrome is caused a tumor of gastrin secreting cells of pancreas characterized by excessive secretion of gastrin that stimulates gastric acid secretion. The disorders can be treated by drugs, which are able to: Neutralize gastric acid (HCl) e.g. magnesium hydroxide Reduce gastric acid secretione.g. cimetidine Enhance mucosal defences e.g sucralfate

Exert antimicrobial action against H.pylori e.g. clarithromycin

The most commonly used antacids:are mixtures of aluminium hydroxide and magnesium hydroxide (e.g. Gelusil, Maalox etc). Antacids act primarily in the stomach and are used to prevent and treat peptic ulcer. They are also used in the treatment of Reflux esophagitis and Gastritis B. Gastric acid secretion inhibitors (antisecretory drugs): HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine, histamine and gastrin that stimulate the secretion.

II. Laxatives and cathartics (purgatives)Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel elimination (defecation). The term laxative implies mild effects, and eliminative of soft formed stool. The term cathartic implies strong effects and elimination of liquid or semi liquid stool. Both terms are used interchangeably because it is the dose that determines the effects rather than a particular drug.

Indications for Laxatives and cathartics: 1. To relieve constipation 2. To prevent straining stool softeners 3. To empty the bowel in preparation for bowel surgery or diagnostic procedures (saline or stimulant) 4. To accelerate elimination of potentially toxic substances from the GI tract (saline or stimulant) 5. To accelerate excretion of parasite after anthelmintic drugs (saline or stimulant) have been administered. Constipation is a common problem in older adults and laxatives are often used or overused. Non drug measures to prevent constipation (e.g. increasing intake of fluid and high fiber foods, exercise) are much preferred to laxatives.

III. Antidiarrhoeals:

Are used in the treatment of diarrhea, defined as the frequent expulsion of liquid or semi liquid stools hinders absorption of fluids and electrolytes. In many instances, drug intervention is not required because is a protective mechanism used in an attempt by the body to flush out the offending pathogen or agent.

Antidiarrheal drugs may be given to relive the symptom (non-specific therapy) or may be given to treat the underlying cause of the symptom (specific therapy).For symptomatic treatment of diarrhoea, opiates and opiate derivatives are the most effective. They decrease diarrhea by slowing propulsive movements in small and large intestine.

Morphine is effective but not used because of serious potential adverse effects, other synthetic drugs such as diphenoxylate and loperamide are commonly used Adsorbent demulcent products such as kaolin pectin preparation may be included in antidiarrheal preparations, unfortunately, they may adsornutrient and other drugs, including the antidiarrheal agents if given concurrently Anticholinergic agents e.g. atropine are occasionally used to decrease abdominal cramping and pain associated with diarrhea.

Specific therapy may include the use of antibacterial, which are recommended for use in carefully selected cases of bacterial enteritis. Severe diarrhea by salmonella, shigella, campylobacter and clostridia. Species can be treated by antibiotics (ampicillin, chloramphinicol, colistin, co-trimoxazole etc.

Indications for use:1. severe or prolonged diarrhea (>2-3 days) 2. when specifice causes have been determined

IV. Antiemetics:Are drugs used to prevent or treat nausea and vomiting.Nausea is an unpleasant sensation of abdominal

discomfort accompanied by a desire to vomit. Vomiting is the expulsion of stomach contents through the mouth Nausea may occur without vomiting and vomiting may occur without prior nausea, but the two symptoms most often occur together.Vomiting occurs when the vomiting center in the medulla oblongata is stimulated. Dopamine and acetylcholine play a major role in stimulating the vomiting center. To a certain extent, vomiting is a protective mechanism which can result from various noxious stimuli.

Drugs used in nausea and vomiting: belong to several different therapeutic classifications. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting center, CTZ, cerebral cortex, vestibular apparatus, or a combination of these. Antiemetic drugs are generally more effective in prophylaxis than treatment. Antiemetic drugs include: Phenothiazines (neuroleptics) such as chlorpromazine Acts on CTZ and vomiting center Block dopamine receptors Are effective in prevention or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy). Are generally ineffective in motion sickness.

Antihistamines such as promothazine, dimehydrinate etc. Are especially effective in prevention and treatment of motion sickness (but they may cause concurrent drowsiness, that may be troublesome for travellers) .

Miscellaneous antiemetics: Metoclopramide has both central and peripheral antiemetic effects. Centrally, metoclopoamide antagonizes the action of dopamine. Peripherally metoclopoamide stimulates the release of acetylcholine, which in turn, increases the rate of gastric emptying (used in esophapeal reflux)

Indication; as chlorpromazine Scopolamine, an anticholinergic drug is very effective in reliving nausea & vomiting associated with motion sickness.

Ondansetron- is serotonin antagonist (5-HT3 receptors) found on the afferent fibers of the vagus nerve and in parts of the brain associated with CTZ. Controls chemical induced vomiting and nausea.

V. Drugs used to induce vomitingIn case of poisoning with noncorrosive agents, and assuming incomplete absorption of the poison has taken place, induction of vomiting can be carried out. The drug used for this purpose is emetine, the active ingredient of ipecacuanha (syrup of ipecac). Emetine induces by direct irritation of the upper gut and on absorption, it also acts on CTZ.

VI. Drugs used in the treatment of haemorrhoids;Haemorrhoids are varicose veins of the anal canal which can be very distressing for the sufferer. There is no pharmacological cure for this disorder, which is often self-limiting, if not, may require surgical intervention.

The use of drugs may however, linder the sufferings: Stool softeners may alleviate constipation; lessen straining which can worsen the condition. Local anesthetics (e.g. lignocaine, benzocaine) relieve pain Corticosteroids (e.g. predniosolone) suppress inflammation, itching & swelling Vasoconstrictors (e.g. adrenaline, phenylephine) lessen venous swelling Astringent compounds (e.g. tannic acid) reduce swelling by precipitating cell surface proteins. Antihaemmorhoidal preparations contain one or more of these agents.

VII. Drugs used in inflammatory bowel disease (ulcerative colitis and crohns disease)

Ulcerative colitis is an inflammatory condition of the rectum and colon; crohns disease can involve the whole intestine. Both diseases can lead to pain and abdominal

discomfort. Two groups of drugs used to treat both conditions are 1. corticosteroids e.g. prednisolone 2. drugs related to sulphonamides e.g. sulfasalazine.

ADULT HEALTH (FRIDAY)

Rickettsial diseases

Definition: Rickettsiae are small intracellular bacteria that are spread to man by arthropod vectors, namely human body lice, fleas, ticks & larval mites. The organisms inhabit the gastrointestinal tract of

these arthropods & spread to human host by the direct bite of the vector or the inoculation of the organism contained in the feces of the vector by bite induced body itching. These infections are characterized by persistence in the body, widespread vasculitis (invading endothelial cells of small blood vessels) & multi-system involvement. Except in louse borne typhus humans are accidental hosts in most rickettsial diseases.

Classification:

Rickettsial diseases are classified into five general groups;

• Tick and mite borne spotted fever group

• Flea and louse borne typhus group • Chigger borne scrub typhus

• Ehrlichiosis

• Q-fever.

Etiology and Epidemiology of Epidemic and Endemic Typhus :

Epidemic Typhus (Louse born );

Is caused by R.prowazekii and transmitted by human body louse (Pediculus humanus corporis). Lice acquire the rickettsiae while ingesting a blood meal from an infected patient, the rickettsiae multiply in the midgut epithelial cells of the louse and are excreted via louse faeces. The infected louse defecates during a blood meal and the patient autoinoculates the organisms

by scratching. It is commonly associated with poverty, cold weather, war and natural disasters. The disease is prevalent in mountainous areas of Africa, South America, and Asia.

Endemic Typhus (Flea born) / Murine Typhus;

Is cause by R. thyphi which is transmitted by fleas. R.typhi is maintained in mammalian host/flea cycles, with rats. Fleas acquire R.typhi from rikettsemic rats and carry the organism throughout the rest of their life span. . Humans and rats are infected when rickettsiae –laden fleas are scratched in to pruritic bite lesions.

Pathophysiology:

In man rickettsiae multiply in the endothelial cells of capillaries causing lesions in the skin, brain, lung, heart, kidneys and skeletal muscles. Endothelial proliferation coupled with peri-vascular reaction causes thromboses and small hemorrhages. However, tissue and organ injury is commonly due to increased vascular permeability with resulting edema, hypovolemia and organ ischemia. This leads to multi-system involvement with complications such as non-cardiogenic pulmonary edema, cardiac dysrhythemia, encephalitis, renal and hepatic failure and bleeding.

Clinical Features:

Signs and symptoms;

• Incubation period of 1 week

• Abrupt onset of illness with prostration, severe headache and rapidly rising fever of 38.8 to 40.0 °C

• Cough s seen in 70 % of patients , myalgia may also occur which may be severe • Rash, begins on upper trunk around 5th day and then becomes generalized, involving the entire body except face, palms and soles; at first, rash is macular, becoming maculopapular, petechial and confluent without treatment, although in black people, rash may be absent (spotless epidemic typhus)

• Photophobia, with conjunctival injection and eye pain; frequent

• Tongue may be dry, brown, furred

• The signs of central nervous system involvement, commonly as meningo-encephalitis, appear towards the end of the 1st week progressing to seizure and coma.

Brill-Zinsser disease (recrudescent typhus);

This is a mild form of epidemic typhus caused by reactivation of dormant R. prowazekii in the body (in the lymph nodes) as a result of Immunosuppression or old age. Occurs after several years of acute infection. The manifestation of the disease is similar to acute epidemic typhus but milder. The organisms may infect other people in the presence of vectors (body lice).

Endemic typhus (Flea borne typhus);

• Epidemic typhus (also known as murine typhus) is a relatively milder.

• The incubation period is 1 - 3 weeks and followed by sudden onset of fever, rigors, frontal headache, pain in the back and limbs, constipation and cough (due to bronchitis).

• The fever becomes constant after the third day and associated with conjunctivitis and orbital pain.

• Rash appears on the fifth day initially as blanching macules at the anterior axillary folds, which subsequently spread to involve other parts of the body (sparing the face & the neck) and become purpuric.

• During the second week symptoms worsen and additional manifestations, such as sore lips, dry brown tremulous tongue, feeble pulse, enlarged spleen & delirium appear.

Complications of Endemic and Epidemic Typhus:

Skin necrosis, gangrene of digits, Venous thrombosis, Interstitial pneumonia in severe cases,Myocarditis,Oliguric renal failure and Parotitis.

Diagnosis of rickettsial diseases is based on History, clinical course of the disease and epidemiologic of the disease may give a clue for diagnosis.

Laboratory investigations:

Serologic tests;

• Indirect fluorescent antibody test

• Weil-Felix agglutination test: Not specific or sensitive. Isolation of the organism by inoculation into laboratory animals is possible, it is time consuming and technically demanding.

Treatment of rickettsial diseases:

Endemic Typhus;

*Doxycycline 100mg bid PO for 7-15 days

* Chloramphenicol 500mg QID PO for7-15 days.

Epidemic typhus;

*Doxycycline 200mg as single dose PO until the patient is afebrile for 24 hours.

*Delousing louse borne typhus

* Supportive Therapy: Attention to fluid balance, prevention of bed sores. Treat agitation with diazepam Steroid treatment (prednisolone 20 mg daily for adults) in severe cases.

Prognosis:

Untreated disease is fatal in 7 to 40 % of cases, depending on condition of host. In untreated survivors, renal insufficiency, multiorgan involvement and neurologic manifestations (12 %) are common. However, endemic typhus has better prognosis with a mortality of only 1 – 2%. Serious neurological, renal and other complications are unusual.

Prevention For flea borne typhus:

*Elimination of fleas on clothing & bedding using insecticides like 1% Malathion powder. Apply residual insecticide powder on the floor & bedding to kill hatching fleas. Rodent control using chemicals (e.g. warfarin).

For louse borne typhus;

*Eradicate all lice on clothing & bedding using insecticides (1% Malathion powder) including all family contacts. DDT is not useful as the lice are often resistant to it

*Wash the patient with soap and water & apply insecticides all over & disinfect clothing with insecticides in a bag or sterilize by autoclaving.

*Protective wearing smeared with insect repellents is recommended for nurses and other attendants.

Chemoprophylaxis: Doxycycline 100mg weekly will protect those at risk. walesonmd@gmail.com