Antiprotozoal and Anthelmintic Drugs — Metronidazole, Albendazole, Ivermectin, Praziquantel and Drug of Choice

Antiprotozoal drugs act on single-celled parasites such as Entamoeba, Giardia, Trichomonas, Leishmania and trypanosomes. Anthelmintics act on worms: nematodes (roundworms), cestodes (tapeworms) and trematodes (flukes). For exams the useful grouping is by drug class, with the parasite spectrum, the mechanism and one characteristic adverse effect.

Metronidazole enters the organism by diffusion, is reductively activated inside it, and then interacts with DNA, causing loss of helical structure and strand breakage and cell death. Although it diffuses into aerobic and anaerobic organisms, its antimicrobial effect is limited to anaerobes. It crosses the blood–brain barrier.

Adverse effects include confusion, peripheral neuropathy, a metallic taste, nausea, vomiting and diarrhoea. Patients should avoid alcohol during treatment and for at least 48 hours afterwards because of a disulfiram-like reaction (flushing, tachycardia, palpitations, nausea and vomiting). Metronidazole is contraindicated with recent disulfiram use (within the past 2 weeks) and should be avoided in the first trimester of pregnancy. A full blood count is monitored in prolonged courses. See also amoebic vs pyogenic liver abscess and vaginitis.

These haemoflagellate infections use a distinct set of antiprotozoal drugs. The full clinical picture is on leishmaniasis and haemoflagellates; the pharmacology summary is below.

Albendazole is converted to the active albendazole sulfoxide, which binds the β-tubulin subunit of the worm's microtubules and inhibits polymerisation. It also impairs glucose utilisation and depletes glycogen stores, leading to energy depletion, immobilisation and death of the parasite. Mebendazole also works by inhibiting microtubule production, binding the colchicine-binding site of β-tubulin; it is poorly absorbed, which makes it effective for intestinal worms with few side effects.

WHO recommends albendazole 400 mg or mebendazole 500 mg for periodic deworming of school-age children in endemic areas for roundworm, whipworm and hookworm. Strongyloides behaves differently: WHO notes it is not sensitive to albendazole or mebendazole campaigns, and ivermectin is used instead.

• Albendazole adverse effects: headache, raised liver enzymes in 10% to 20%, abdominal pain, nausea and vomiting, rarely leukopenia, anaemia or pancytopenia; check liver function and blood counts in prolonged courses.
• Pregnancy: albendazole was FDA pregnancy category C; avoid unless there is no acceptable alternative.
• Neurocysticercosis: killing larvae provokes inflammation, so corticosteroids and anticonvulsants are co-administered. See neurocysticercosis.
• Interactions: CYP450 inducers (phenobarbital, phenytoin, rifampin, carbamazepine) can lower albendazole levels by up to 50%; avoid combining mebendazole with metronidazole.
• Mebendazole: contraindicated for mass treatment under 1 year because of convulsion reports.

Ivermectin acts on glutamate-gated chloride channels (GluCl) of invertebrates, a class of pentameric ligand-gated ion channels. It is the drug of choice for strongyloidiasis and onchocerciasis.

For mass treatment of lymphatic filariasis, WHO recommends: albendazole alone twice a year where loiasis is co-endemic; ivermectin 200 µg/kg + albendazole 400 mg where onchocerciasis occurs; DEC 6 mg/kg + albendazole 400 mg in countries without onchocerciasis; and, where programme conditions allow, ivermectin + DEC + albendazole (triple-drug therapy).

Praziquantel is the treatment of schistosomiasis, effective against all major human Schistosoma species. It increases the permeability of the parasite's membrane to calcium ions, producing paralysis and death of adult worms, which reduces egg deposition and the resulting fibrosis and urogenital damage. Standard regimens are 40 mg/kg orally as a single dose, or 20 mg/kg every 4 to 6 hours for 3 doses (total 60 mg/kg).

• It does not kill immature worms or eggs, so efficacy is best when given at least 4 to 6 weeks after exposure.
• Resistance has been reported in some species; S. mansoni has shown resistance to standard doses.
• It is generally well tolerated and was classed as FDA pregnancy category B, so it can be used in endemic populations including pregnant women.

Related pages: practise previous papers at NEET PG Pharmacology PYQs and NEET PG Microbiology PYQs, and see the most repeated topics. Related reading: intestinal nematodes and hookworm.

The categories quoted here are the older FDA pregnancy letters that StatPearls still cites; current labels use narrative risk summaries, so in practice always check the present guideline before prescribing in pregnancy.

• Albendazole and mebendazole inhibit β-tubulin (microtubules), not ergosterol or folate synthesis.
• Ivermectin acts on glutamate-gated chloride channels; screen for Loa loa before use in Africa.
• Praziquantel increases calcium permeability and does not kill immature schistosomes.
• Metronidazole + alcohol = disulfiram-like reaction; avoid in the first trimester.
• Strongyloides: ivermectin is first line; albendazole is second line.
• Neurocysticercosis: give steroids and anticonvulsants with albendazole.
• Eflornithine treats gambiense, not rhodesiense, sleeping sickness; melarsoprol is the arsenical for second-stage rhodesiense disease.