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Anthelmintics

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Anthelmintics

       Classification

       Pharmacology

At the end of this lecture, the student will be able to:

       Classify anthelmintic drugs

       Describe the pharmacology of Anthelmintics

Anthelmintics

       Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting helminths

Chemotherapy for helminthic infection

       Broad spectrum Anthelmintics – Benzimidazole group

      Thiabendazole

      Mebendazole

      Albendazole

      Triclabendazole

       Against Nematodes

      Pyrantel pamoate

      Levamisole

      Piperazine

      Diethyl carbamazine

      Ivermectin

      Thiabendazole

      Doxycycline

       Against Trematodes

      Metrifonate

      Oxamniquine

      Bithionol

      Triclabendazole

       Against Cestodes

      Niclosamide

       Against Trematodes + Cestodes

      Praziquantel

Benzimidazoles

       Broad spectrum anthelmintics

       Binds to β-tubulin filaments of helminths

       Prevents polymerisation leading to breakdown of cytoplasmic microtubules

       Selective and irreversible inhibition of glucose uptake

       Depletion of parasitic glycogen storage

       Reduced formation of ATP and disrupted metabolic pathway

       Parasitic death

Albendazole
Broad spectrum oral anthelmintic

Pharmacokinetics

       Variable oral absorption

       Fatty meal increases absorption by 5 folds

       Metabolised in liver to active sulfoxide metabolite

       Distribution  - Bile, CSF and hydatid cysts 

       Elimination half-life – 8-12 h

Clinical Uses of Albendazole

       Effective against intestinal nematodes, cestodes and liver fluke

       Drug of choice for round worm, whip worm, hook worm

       Dose – Adult and children above 2 yrs – 400 mg single dose at night

      Children 1-2 yrs – 200 mg OD

For heavy worm infestation – dose repeated 3 days

       Alternative drug for the treatment of

      Strongyloides stercoralis (thread worm) – 400 mg OD for 3 days

      Enterobius vermicularis (pin worm) – 400 mg OD to be repeated after 2 weeks

       Synergistic combination with diethyl carbamazine or ivermectin for treating or controlling lymphatic filariasis

Adverse effects of Albendazole

       Well tolerated

       Side effects are rare for a short period

       If used for 3 months

      Epigastric distress

      Headache

      Alopecia

      Fatigue

      Insomnia

       Teratogenic in animals, long term use in pregnancy is avoided

Mebendazole

       Prototype benzimidazole with wide spectrum anthelmintic activity

Pharmacokinetics

       Oral absorption is erratic (10%)

       Absorption is increased with fatty meal

       Metabolised to decarboxylated metabolite in liver

       Excretion – Urine, little amount in bile

       Half-life – 2-6 h

Clinical Uses of Mebendazole

       For treatment of round worm, hook-worm and Whip-worm infestation

       Dose – 100 mg BD for 3 days

       95-100% cure rate in pin worm infestation

       Used for mixed infections (ascaris + hook worm or ascaris + hook worm + whip worm)

       Alternative drug for the treatment of intestinal capillariasis, visceral larva migrans and Taenia saginata

Adverse effects of Mebendazole

       Abdominal discomfort , nausea, vomiting & diarrhoea

       Higher doses – Rash, Urticaria, elevated aminotransferase

       CI in liver cirrhosis

       Teratogenic in few animal species

       CI in pregnancy

Summary

       Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting helminths

       Classified based on their action against different helminths

       Benzimidazole derivatives are broad spectrum anthelmintics used against nematodes, cestodes and trematodes

       Other drugs include pyrantel pamoate, piperazine, diethyl carbamazine, piperazine, niclosamide, praziquantel

 

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