Lecture 18: Antiprotozoal and Antihelmintic Drugs

Metronidazole

Drug of choice for E. histolytica, G. lamblia, & T. vaginalis

Invasive amebiasis - Metronidazole + luminal amebicide

Reduced by reacting with reduced ferredoxin (only found in anaerobes) → metabolites are taken up into DNA → form unstable molecules

Oral, IV, topical

Liver metabolism; Eliminated in the urine

Kills amoeba in tissues (trophozoites)

Dysgeusia (metallic taste)

Disulfiram-like reaction

Tinidazole

DOC option for G. lamblia – single oral dose

Luminal amebicides

Asymptomatic infections - paromomycin or iodoquinol

Symptomatic, invasive intestinal disease or extraintestinal infections- metronidazole followed by treatment with paromomycin or iodoquinol

Tetracycline & Erythromycin

Paromomycin

Aminoglycoside

Oral, cream

Luminal trophozoites (amebicide) - not significantly absorbed from GI tract

Effective for asymptomatic amebiasis (or with metronidazole for symptomatic amebiasis)

GI upset, superinfection

Iodoquinol

Effective against luminal trophozoites and cysts

poorly absorbed and remains primarily in the intestinal lumen

Oral

high iodine content – iodine-induced thyroid enlargement, nail/hair/skin/sweat discoloration

optic neuritis and optic atrophy

Toxoplasma gondii

Self limited in immunocompetent

Chronic maintenance therapy should be initiated in pt with CD4 count <200

Preferred treatment and maintenance: Pyrimethamine plus Sulfadiazine or Clindamycin

Alternate: Sulfamethoxazole/trimethoprim

Alternate (sulfa hypersensitivity): atovaquone

Pyrimethamine

Treatment of choice, oral

inhibition of folate metabolism and protein synthesis

Administer with leucovorin to prevent hematologic toxicity

Trimethoprim plus Sulfamethoxazole

Drug of choice for pneumocystis pneumonia (PCP) treatment

prophylaxis in AIDS patients, transplant

inhibition of folic acid synthesis

Hypersensitivity, SJS, photosensitivity

Pentamidine

Alternate for the treatment of P. jirovecii

inhibits DNA replication

IV (active infection) or nebulization (prophylaxis)

Toxicity: hypotension, arrhythmias, hypoglycemia

Usually reserved for use in patients who don't tolerate trimethoprim/sulfamethoxazole

Atovaquone

used for toxoplasmosis and PCP

Roundworms (nematodes)

Albendazole or mebendazole or pyrantel pamoate

Flukes (trematodes) or Tapeworms (cestodes)

Praziquantel

Albendazole and Mebendazole

oral

broad-spectrum

mixed roundworm infections

inhibits microtubule polymerization by binding to β- tubulin → inhibit microtubule-dependent uptake of glucose

teratogenic

abdominal discomfort and diarrhea

LFT

Pyrantel Pamoate

broad-spectrum

MOA: Cholinesterase inhibitor → depolarizing neuromuscular blockade

Toxicity - flu-like symptoms

Available OTC

Praziquantel

oral

Well-absorbed from the GI tract -used for systemic infections

increases worm’s permeability to Ca2+ → contraction and paralysis of worm's muscles

Toxicity - nausea, vomiting and abdominal discomfort from release of dead worms’ proteins