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Antiamoebic drugs
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- 2. AMEBIASIS Amebiasis (also calledamebic dysentry) is an infection of intestinal tract caused by Entamoeba histolytica. The disease can be acute or chronic, with the patients showing varying degrees of illness, from no symptoms to mild diarrhea to fulminating dysentery (Dysentery in which the symptoms are intensely acute, leading to prostration, collapse, and often death).
- 3. The diagnosis isestablished by isolating E. histolytica from fresh feces. Therapy is aimed not only at the acutely ill patients but also at those who are asymptomatic carriers, because dormant E. histolytica may cause future infections in the carrier and be a potential source of infections for others.
- 4. Protozoal infections arecommon among the people in underdeveloped topical and subtropical countries, where sanitary conditions, hygienic practices and control of vectors of transmission are inadequate.
- 5. Life cycle of Entamoebahistolytica Entamoeba histolytica exists in two forms: 1. Cysts form (That can survive out side the body). 2. Trophozoites form (That are labile and don’t persist outside the body). Life cycle Life cycle consists of following steps:
- 6. 1. Ingestion ofcysts Cysts are ingested through feces, contaminated food or water. 2. Formation of trophozoites Cysts are passed into the lumen of intestine, where the trophozoites are liberated. 3. Penetration and multiplication of trophozoites Trophozoites are penetrated in intestinal wall and multiply within colon wall. They either invade and ulcerate the mucosa of large intestine or simply feed on intestinal bacteria.
- 7. 4. Systemic invasion Largenumbers of trophozoites within the colon wall can also lead to systemic invasion and caused liver abscess. 5. Cysts discarded The trophozoites within the intestine are slowly carried toward the rectum, where they return to cyst form and are excreted in feces.
- 9. Classification of amebicidal drugs Accordingto the site where the drug is effective, the amebicidal drugs are classified as: • Luminal amebicides (Act on parasite in the lumen of bowel) • Systemic amebicides (Against amebas in intestinal wall & liver) • Mixed amebicides ( Against both the luminal and systemic form of diseases).
- 10. MIXED AMEBICIDES 1. Metronidazole(Flagyl) • Mixed amebicides are used for the treatment of amebic infections; it kills the E. histolytica trophozoits. • Extensively used in the treatment of infections caused by Giardia lamblia, Trichomonas vaginalis, Anaerobic cocci, and Anaerobic gram negative bacilli.
- 11. • Drug ofchoice for the treatment of pseudomembranous colitis caused by the anaerobic, gram positive bacillus Clostridium difficile. • Activated by anaerobic organisms to a compound that damage parasite DNA.
- 12. Mechanism of actionof Metronidazole Metronidazole is a prodrug. It requires reductive activation of nitro group by susceptible organism. Its selective toxicity towards anaerobic and microaerophilic pathogens such as E. histolytica, G. lamblia, etc. These organisms contain electron transport components such as ferridoxin, small Fe-S proteins that have sufficiently negative redox potential to donate electrons to metronidazole.
- 13. The single electrontransfer forms a highly reactive nitro radical anion that kills susceptible organisms by radical-mediated mechanisms that target DNA, resulting in cell death.
- 14. Mechanism of actionof Metronidazole
- 15. Pharmacokinetics Absorption Metronidazole is usuallygiven orally and it is rapidly and completely absorbed achieving peak plasma concentration in 1-3 hours, with half life of about 7 hours. Distribution It is distributed rapidly throughout the tissues, reaching high concentration in the body fluids, including cerebrospinal fluid.
- 16. Metabolism Metabolism of metronidazoleoccurs in liver. Excretion The parent drug and its metabolites are excreted in the urine. Contraindication: Phenobarbital is the inducer of this enzymatic system so it enhances the rate of metabolism when used concomitantly. Cimetidine inhibit this system so it prolongs the plasma half life of metronidazole.
- 17. Adverse effects: An unpleasantmetallic taste is often experienced. The most common adverse effects are those associated with the gastrointestinal tract, including nausea, vomiting, epigastric distress, and abdominal cramps. Urine:-dark/reddish-brown.
- 18. Tinidazole: Tinidazole is asecond-generation nitroimidazole that is similar to metronidazole in spectrum of activity, absorption, adverse effects and drug interactions. It was approved by the U.S. Food and Drug Administration in 2004 for the treatment of amebiasis, amebic liver abcess,
- 19. giardiasis and trichomoniasisbut was used outside the United States for decades prior to approval. Tinidazole is as effective as metronidazole, with a shorter course of treatment, yet is more expensive than generic metronidazole.
- 20. Iodoquinol Iodoquinol, ahalogenated 8- hydroxy quinolone. It is effective against Entamoeba histolytica, luminal trophozite and cyst form. Side effects include rashes, diarrhea, dose- related neuropathy, including rare optic neuritis. Long term use of drug should be avoided.
- 21. Paromomycin Aminoglycosides antiamebicides;alternative agent for cryptosporidiosis. Not significantly absorbed from GIT, so effective against the intestinal (luminal) form of E. histolytica and tapeworm. Excreted in urine. Its antiamebic action is due to effect on cell membranes, causing leakage and by reducing the population of intestinal flora.
- 22. Adverse effects: Gastrointestinal distress Diarrhea
- 23. SYSTEMIC AMEBICIDES These drugsare useful in treating liver abscesses or intestinal wall infections caused by amebas. Chloroquine: Used in combination with metronidazole and diloxanide furoate to treat and prevent amebic liver abscesses. It eliminates trophozoites in liver abscesses. Also effective in treatment of malaria.
- 24. Emetine and Dehydroemetine: Usedas alternative agents for the treatment of amebiasis. These inhibit protein synthesis by blocking chain elongation. Intramuscular injection is the preferred route. Emetine is concentrated in liver, where it persists for a month after single dose.
- 25. It isslowly metabolized and excreted, and it can accumulate. Its half life in plasma is 5 days. The use of these, are limited by their toxicities and close clinical observations is necessary when these drugs are administered. They should not be taken for more than 5 days.
- 26. Dehydroemetine isonly available under a compassionate investigational new drug protocol through the Centers of disease Control and Prevention. The untoward effects are pain at the site of infection, transient nausea, cardiotoxicity, neuromuscular weakness, dizziness, and rashes.