USMLE1 Anti-Protozoal drugs-1

Protozoal diseases

•         Amebiasis and Balantidial Dysentery

•         Trichomoniasis and Giardiasis

•         Leishmaniasis and Trypanosomiasis

1. Amebiasis (E. histolytica)

Diseases caused by E. histolytica:  

•         Asymptomatic cysts carriers

•         Diarrhea / Dysentery

•         Amebic liver abscess

Route of transmission:

•         E. histolytica is a water-borne pathogen transmitted by the fecal-oral route.

E. histolytica exists in two forms   

Cysts – that can survive outside the body

Trophozoites – do not persists outside the body but invasive.

Anti - Ameobic Drugs

Luminal amebicidal drugs:

•         Diloxanide furoate

•         Iodoquinol

•         Tetracycline/Doxycycline/Azythromycin

•         Paromomycin (aminoglycoside)

Systemic amebicidal drugs :

•         Chloroquine

•         Emetine

•         Dihydroemetin

Mixed: Luminal / Systemic amebicidal drugs :

•         Metronidazole

•         Tinidazole

•         Secnidazole

•         Ornidazole

Clinical uses of Mixed Drugs:

•         Broad spectrum cidal activity against = Protozoa – E.histolytica, T.vaginalis, G.lamblia

•         Anaerobic bacteria – B.fragilis, C.perfringes, H.pylori, C. Difficile.

Metronidazole:

MOA: Metronidazole, a nitroimidazole, is the mixed amebicide of choice for treating amoebic infections. The nitro group of metronidazole is able to serve as electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA to result in cell death.

•         Widely distributed in the body secretions – semen, saliva and CSF

•         Metabolized by oxidation and glucuronide conjugation and excreted in urine.

Clinical uses:

1. Antiprotozoal: Metronidazole is DOC for most infections caused by E. histolytica, Giardia species, and Trichomonas vaginalis.

2. Antibacterial: DOC for most anaerobic infections including those caused by B.fragilis, C.difficile and Gardnerella vaginalis.

3. Used in regimens for H.pylori-associated GI ulcers. (MOC-Omeprazole, Metronidazole, Clarithromycin)

Adverse Effects:

•         Nausea, vomiting, epigastric distress, abdominal cramp

•         Unpleasant metallic taste are most common

•         Neurotoxicity : dizziness, vertigo, numbness or paresthesias in the PNS

•         If taken with alcohol, a disulfiram-like effect

•         Seizures at high dose

Contra-indications:

•         First trimester of pregnancy

•         Chronic alcoholism.

Tinidazole:

•         It was approved by the U.S. Food and Drug Administration in 2004 for treatment of amebiasis, amebic liver abcess, giardiasis, and trichomoniasis but was used outside the United States for decades prior to approval.

Diloxanide furoate :

•         Effective luminal amebicidal – kills trophozoites – responsible for the cyst production

•         No anti-bacterial activity

•         Diloxanide is weaker ameobicidal than furoate ester.

•         High cure rates in mild intestinal amoebiasis and asymptomatic cyst passers

Iodoquinol :

•         Amebicidal against luminal trophozoites and cysts

•         Adverse effects includes – peripheral neuropathy and optic neuritis.

Paromomycin :

•         Aminoglycosides which is not absorbed from GIT.

•         Effective against luminal forms of E.  Histolytica – directly

•         It acts indirectly by reducing the intestinal flora also.

Emetine :

•         Inhibit protein synthesis by blocking chain elongation.

•         It is concentrated in the liver

•         administered by i.m injection.

•         Adverse effects includes cardiotoxicity and neuromuscular weakness.