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Protozoal infections Amebiasis Malaria Giardiasis Leshmaniasis Toxoplasmosis Trypanosomiasis

Protozoal infections Amebiasis Malaria Giardiasis Leshmaniasis Toxoplasmosis Trypanosomiasis. Protozoal infections Difficult to be treated than bacterial infections. Protozoal cells ( Eukaryotes) have metabolic processes closer to human host than prokaryotic bacterial pathogens.

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Protozoal infections Amebiasis Malaria Giardiasis Leshmaniasis Toxoplasmosis Trypanosomiasis

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  1. Protozoal infections Amebiasis Malaria Giardiasis Leshmaniasis Toxoplasmosis Trypanosomiasis

  2. Protozoal infections • Difficult to be treated than bacterial infections. • Protozoal cells (Eukaryotes) have metabolic processes closer to human host than prokaryotic bacterial pathogens. • Many of antiprotozoal drugs cause toxic effects on the host. • Cells with high metabolic processes in the host are susceptible. • Examples: bone marrow stem, renal tubular cells, intestinal & neuronal cells. • Antiprotozoal are not safe during pregnancy.

  3. Antiprotozoal Drugs Chemotherapy for amebiasis Chemotherapy for malaria Chemotherapy for giardiasis Chemotherapy for leshmaniasis Chemotherapy for toxoplasmosis Chemotherapy for trypanosomiasis

  4. AMOEBIASIS

  5. Amebiasis Amebiasis is a protozoal infection of the intestinal tract that occurs due to ingestion of foods or water contaminated with Entameba Histolytica cysts

  6. LIFE CYCLE • Entamoeba histolytica exists in two forms: • Cysts (infective): • can survive outside the human body. • transform to trophozoites. • 2. Trophozoites (non-infective; invasive): • Can reproduce • They may feed on intestinal bacteria or invade and ulcerate wall of large intestine, and may migrate to liver or other tissues. • transform to cysts which are excreted in feces.

  7. Life Cycle • Cysts ingestion. • Formation of trophozoites • Penetration of intestinal wall • Multiplication of trophozoites within colon wall. • Systemic invasion. • Cyst formation in rectum and excretion in feces.

  8. LIFE CYCLE

  9. Clinical presentations Asymptomatic Intestinal infection (Carriers, passing cysts) Mild to moderate intestinal disease (Nondysenteric Colitis) Severe Intestinal infection (Dysentery) Hepatic abscess, ameboma (localized granulomatous lesion of colon) and other extraintestinal disease

  10. PATHOGENESIS OF AMOEBIASIS

  11. ANTIAMEBIC DRUGS ▪Luminal Amebicides ▪ Tissue or systemic amebicides ▪ Mixed Amebicides

  12. LUMENAMOEBICIDES • Acts on the parasites in the lumen of the bowl. • used for treatment of asymptomatic amebiasis. Include • Diloxanide Furoate • Iodoquinol • Antibiotics - Paromomycin - Tetracyclines - Erythromycin

  13. Tissue Amoebicides (systemic) acts on the intestinal wall and liver (or any other extra-intestinal tissue). Used for treatment of systemic form of the disease (intestinal wall infection or liver abscesses). Emetine Dehydroemetine Chloroquine (liver only)

  14. Mixed amoebicides Effective against both luminal and systemic forms of the disease. Although luminal concentration is too low for single drug –treatment. • Metronidazol • Tinidazole

  15. METRONIDAZOLE • Mixed amoebicide. • Drug of choice for intestinal & extraintestinal amoebiasis. • Acts on trophozoites. • Has no effect on cysts. • Nitro group of metronidazole is reduced by protozoan leading to cytotoxic reduced product that binds to DNA and proteins resulting into parasite death.

  16. Pharmacokinetics • Given orally or IV. • Absorption is rapid and complete. ▪ Due to rapid absorption from GIT, not reliably effective against luminal parasites. • Wide distribution to all tissues and body fluids (CSF, saliva, milk). • Plasma protein binding is low ( < 20%). • Plasma half life is 8 h

  17. Pharmacokinetics • Metabolized in liver by mixed function oxidase followed by glucouroidation. • Excreted in urine as unchanged drug plus metabolites. • Clearance is decreased in liver impairment. Tinidazole has longer duration, simpler dosing regimen, less toxicity, than metronidazole, but is equally active.

  18. Clinical Uses • Extraluminal amoebiasis (combined with luminal amebicide). • Giardiasis • Trichomoniasis • Broad spectrum of Anaerobic bacteria e.g., • Helicobacter pylori infection • Pseudomembranous colitis (Clostridium defficile).

  19. Adverse effects 1. GIT: • Nausea • Vomiting • Dry mouth • Metallic taste • Diarrhoea • Oral Thrush (Moniliasis, yeast infection).

  20. Adverse effects 2. CNS: Neurotoxicological effect • Insomnia, dizziness • peripheral neuropathy, paresthesia • encphalopathy, convulsion ( IV infusion, rare). 3. Dysuria, dark urine. 4. Neutropenia 5. Disulfiram-like effect if taken with alcohol.

  21. disulfiram like -effect When metronidazole is given with alcohol abdominal distress, nausea, vomiting, flushing, or headache, tachycardia, hyperventilation alcohol aldehyde dehydrogenase dehydrogenase Ethanol Acetaldehyde Acetate

  22. Drug interactions: • Enzyme inhibitors (cimetidine, ketoconazole) increase duration of action of metronidazole • Inducers (phenytoin and phenobarbitone). • inhibits CYP family 2C9 & 3A4 • potentiate anticoagulant effect of warfarin. • potentiates lithium toxicity.

  23. CONTRAINDICATIONS / PRECAUTIONS: ▪ Pregnancy and nursing women. ▪ Alcohol intake ▪ CNS diseases ▪ Severe hepatic disease • Severe renal disease

  24. EMETINE AND DEHYDROEMETINE Chemistry: • Emetine hydrochloride is a plant alkaloid derived from ipeca. • Dehydroemetine is a synthetic analogue Pharmacokinetics: • Erratic oral absorption. • Given preferably subcutaneously but could be given by IM, NEVER I.V. • Plasma half life is 5 days.

  25. EMETINE • Concentrated in Liver, Lungs, Spleen, Kidney, Cardiac muscle and Intestinal wall. • Metabolized & Excreted slowly via kidney so it has a cumulative effect. • Trace amounts could be detected in urine 1-2 month after last dose. • Should not be used for more than 10 days (usually 3-5 days).

  26. Mechanism • Act on tissue trophozoites causing irreversible block of protein synthesis.

  27. Adverse Effects • Dehydroemetine is less toxic than emetine • pain at site of injection, abcesses. • GIT: nausea, vomiting, diarrhoea. • Neuromuscular weakness • Serious toxicities: cardiotoxicity - cardiac arrhythmias, - Hypotension - heart failure

  28. Clinical Uses • Amoebic liver abscess. • Intestinal wall infections. • Severe forms of amebiasis acute amoebic dysentery dehydroemetine is preferable due to less toxicity (3-5 days).

  29. Contraindications • Heart disease • Kidney disease • Pregnancy • Children

  30. Chloroquine • Antiamebic drug • Antimalarial drug • Used in combination with metronidazole and luminal amebicide for amebic liver diseases.

  31. Luminal amoebicides • acts on the luminal parasites • used for treatment of asymptomatic amebiasis. Include Diloxanide Furoate • Iodoquinol • Antibiotics - Paromomycin - Tetracyclines - Erythromycin

  32. Diloxanide furoate Chemistry • Ester of diloxanide + furoic acid . Pharmacokinetics • Given orally. • Split in the intestine, most of diloxanide is absorbed, conjugated to form a glucoronide which is excreted in urine (90%). • The unabsorbed diloxanide is the amoebicidal agent (10%).

  33. Pharmacodynamics: • Unkown mechanism of action • Direct amoebicidal action against luminal forms. • Not active against trophozoites intestinal wall or extraintestinal tissues.

  34. Therapeutic Uses • Drug of choice for asymptomatic intestinal infection. • For eradication of infection given along with all forms of amebiasis. • Dose: 500 mg three times/day for 10 days.

  35. Adverse Effects • Flatulence • Nausea, vomiting, abdominal cramps. • No serious adverse effects Contraindications: - Pregnancy - Children (less than 2 years).

  36. Paromomycin Sulphate • Aminoglycoside, not absorbed. • Effective against luminal forms of ameba Mechanism of action • Direct amebicidal action (causes leakage by its action on cell membrane of parasite). • Indirect killing of bacterial flora essential for proliferation of pathogenic amoebae.

  37. Kinetics • Orally • Not significantly absorbed from the GIT • Small amount absorbed is excreted unchanged in urine (may accumulate with renal insufficiency).

  38. Adverse effects • Gastrointestinal distress and diarrhea. Precautions • Severe renal disease • patients with GIT ulceration

  39. Tetracyclines • Very weak direct amoebicidal action. • Mainly act indirectly on bacterial flora. • Used in severe cases of amoebic dysentery not responding to metronidazole combined with dehydroemetine.

  40. HALOGENATED HYDROXYQUINOLINES • Iodoquinol Mechanism of action • Unknown • Effective against organisms in GIT only Not intestinal wall or liver. Pharmacokinetics • Absorption is poor (90%), excreted in feces. • 10% enter circulation, excreted as glucouronide in urine. • Half life is 11-14 h

  41. Uses • lumen amoebicide. • For eradication of infection given along with tissue amoebicide (metronidazole).

  42. Adverse Effects • Peripheral neuropathy including optic neuritis • GIT: Nausea, vomiting, diarrhoea. • Enlargement of the thyroid gland. • Agranulocytosis. • Iodine sensitivity. • interference with thyroid function tests (increase protein-bound serum iodine, decrease in measured131I uptake).

  43. Contraindications • Optic neuropathy • Thyroid disease • Sensitivity to iodine • Severe liver disease • Severe kidney disease • discontinued if it produces persistent diarrhea or signs of iodine toxicity (dermatitis, urticaria, pruritus, fever)

  44. THANK YOU AND GOOD DAY!

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