Amoebiasis by JITENDRA BHANGALE

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AMOEBIASIS, ANTIAMOEBIC AGENT

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Amoebiasis by JITENDRA BHANGALE

  1. 1. 9/2/2012 By- Jitendra Bhangale Assistant Professor & Head, Department of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad 1 © 2010 Delmar, Cengage Learning 2 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 1
  2. 2. 9/2/2012Amebiasis is a protozoal infection of the intestinal tractthat occurs due to ingestion of foods or watercontaminated with Entameba Histolytica cysts 3 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badEntamoeba histolytica exists in two forms:1. 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. 4 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 2
  3. 3. 9/2/2012 1. Cysts ingestion. 2. Formation of trophozoites 3. Penetration of intestinal wall 4. Multiplication of trophozoites within colon wall. 5. Systemic invasion. 6. Cyst formation in rectum and excretion in feces. 5 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 6 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 3
  4. 4. 9/2/2012 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 7 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 8 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 4
  5. 5. 9/2/2012 Luminal Amebicides Tissue or systemic amebicides Mixed Amebicides 9 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badActs on the parasites in the lumen of the bowl.used for treatment of asymptomatic amebiasis.Include Diloxanide Furoate IodoquinolAntibiotics Paromomycin Tetracyclines Erythromycin 10 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 5
  6. 6. 9/2/2012acts 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) 11 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badEffective against both luminal and systemic forms of thedisease.Although luminal concentration is too low for single drugtreatment. Metronidazol Tinidazole 12 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 6
  7. 7. 9/2/2012Mixed amoebicide.Drug of choice for intestinal & extraintestinalamoebiasis.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. 13 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badPharmacokineticsGiven orally or IV.Absorption is rapid and complete.Due to rapid absorption from GIT, not reliably effectiveagainst 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 14 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 7
  8. 8. 9/2/2012PharmacokineticsMetabolized in liver by mixed function oxidase followedby glucouroidation.Excreted in urine as unchanged drug plus metabolites.Clearance is decreased in liver impairment.Tinidazole has longer duration, simpler dosingregimen, less toxicity, than metronidazole, but is equallyactive. © 2010 Delmar, Cengage Learning 15By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badClinical uses:-Extraluminal amoebiasis (combined with luminalamebicide).GiardiasisTrichomoniasisBroad spectrum of Anaerobic bacteria e.g., Helicobacter pylori infection Pseudomembranous colitis (Clostridium defficile). © 2010 Delmar, Cengage Learning 16By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 8
  9. 9. 9/2/2012Adverse effect:- 1. GIT: Nausea Vomiting Dry mouth Metallic taste Diarrhoea Oral Thrush (Moniliasis, yeast infection). 17 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 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. 18 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 9
  10. 10. 9/2/2012Disulfiram like -effectWhen metronidazole is given with alcohol abdominaldistress, nausea, vomiting, flushing, or headache,tachycardia, hyperventilation 19 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badDrug 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. 20 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 10
  11. 11. 9/2/2012CONTRAINDICATIONS / PRECAUTIONS: Pregnancy and nursing women. Alcohol intake CNS diseases Severe hepatic disease Severe renal disease 21 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badChemistry:Emetine hydrochloride is a plant alkaloid derived fromipeca.Dehydroemetine is a synthetic analoguePharmacokinetics:Erratic oral absorption.Given preferably subcutaneously but could be givenby IM, NEVER I.V.Plasma half life is 5 days. 22 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 11
  12. 12. 9/2/2012Concentrated in Liver, Lungs, Spleen, Kidney, Cardiacmuscle and Intestinal wall.Metabolized & Excreted slowly via kidney so it has acumulative effect.Trace amounts could be detected in urine 1-2 monthafter last dose.Should not be used for more than 10 days (usually 3-5 days). 23 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badMechanismAct on tissue trophozoites causing irreversible block ofprotein synthesis.Adverse effect:-Dehydroemetine is less toxic than emetineGIT: nausea, vomiting, diarrhoea.Neuromuscular weaknessSerious toxicities: cardiotoxicity cardiac arrhythmias, Hypotension, heart failure 24 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 12
  13. 13. 9/2/2012Clinical uses:-Amoebic liver abscess.Intestinal wall infections.Severe forms of amebiasis acute amoebic dysenterydehydroemetine is preferable due to less toxicity (3-5days). 25 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad Contraindication:- Heart disease Kidney disease Pregnancy Children 26 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 13
  14. 14. 9/2/2012Antiamebic drugAntimalarial drugUsed in combination with metronidazole and luminalamebicide for amebic liver diseases. 27 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badacts on the luminal parasitesused for treatment of asymptomatic amebiasis.Include Diloxanide Furoate Iodoquinol Antibiotics Paromomycin Tetracyclines Erythromycin 28 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 14
  15. 15. 9/2/2012Chemistry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 inurine (90%).The unabsorbed diloxanide is the amoebicidal agent(10%). 29 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badPharmacodynamicsUnkown mechanism of actionDirect amoebicidal action against luminal forms.Not active against trophozoites intestinal wall orextraintestinal tissues. 30 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 15
  16. 16. 9/2/2012Therapeutic 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. 31 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badAdverse effect:-FlatulenceNausea, vomiting, abdominal cramps.No serious adverse effectsContraindications:PregnancyChildren (less than 2 years). 32 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 16
  17. 17. 9/2/2012Aminoglycoside, not absorbed.Effective against luminal forms of amebaMechanism of actionDirect amebicidal action (causes leakage by its actionon cell membrane of parasite).Indirect killing of bacterial flora essential forproliferation of pathogenic amoebae. 33 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badKineticsOrallyNot significantly absorbed from the GITSmall amount absorbed is excreted unchanged in urine (may accumulate with renal insufficiency).Adverse effectsGastrointestinal distress and diarrhea.PrecautionsSevere renal diseasePatients with GIT ulceration 34 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 17
  18. 18. 9/2/2012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. 35 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badMechanism of actionEffective against organisms in GIT only Not intestinalwall or liver.PharmacokineticsAbsorption is poor (90%), excreted in feces.10% enter circulation, excreted as glucouronide inurine. Half life is 11-14 h 36 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 18
  19. 19. 9/2/2012Useslumen amoebicide.For eradication of infection given along with tissueamoebicide (metronidazole). 37 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badAdverse effect:-Peripheral neuropathy including optic neuritisGIT: Nausea, vomiting, diarrhoea.Enlargement of the thyroid gland.Agranulocytosis.Iodine sensitivity.interference with thyroid function tests (increaseprotein-bound serum iodine, decrease in measured 131Iuptake). 38 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 19
  20. 20. 9/2/2012Contraindication:-Optic neuropathyThyroid diseaseSevere liver diseaseSevere kidney diseasediscontinued if it produces persistent diarrhea or signsof iodine toxicity (dermatitis, urticaria, pruritus, fever) 39 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad By Jitendra Bhangale 40 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 20

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