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Kaukab Azim, MBBS, PhD Modified by :Israa Anthelminthic Kaukab Azim, MBBS, PhD Modified by :Israa

Commonly encountered nematode (roundworm) infections Onchocerciasis (river blindness) Enterobiasis (pinworm) Ascariasis (roundworm) Filariasis Trichuriasis (whipworm disease ) Hookworm (ancylostoma duodanale) Strongyloidiasis (threadworm)

Commonly encounterd trematode (Flukes) infections Schistosomiasis

Commonly encounterd cestode (Tapeworms) infections Echinococosis (hydatid disease). Taeniasis Cysticercosis

Drugs Benzimidazoles Mebendazole Albendazole Thiabendazole Pyrantel pamoate / Oxantel pamoate Ivermectin Diethylcarbamazine (table salt) Praziquantel

1. Benzimidazole: Mebendazole Mechanism Of Action: Inhibits polymerization of tubulin protein by binding to β-tubulin of intestinal & tegumental cells of worm Also inhibits fumarate reductase important in anaerobic respiration. Loss of cytoplasmic microtubules leads to loss of up-take of microtubule dependent glucose & depletion of glycogen stores; no glucose no ATP; no oxidation-phosphorylation in mitochondria Result: No energy, no mobility, death of worm

Mebendazole Low bioavailability due to poor absorption and due to first pass effect Co-administration with cimetidine increases mebendazole plasma levels Decrease dose in liver impairment Metabolites are active Contraindicated in pregnancy due to teratogenicity & embryotoxicity in animals USES: Effective against 5 nematodes Pin, Round, Whip and hook worms (Necator americanus and Ancylostoma duodenale)

2. Pyrantel Pamoate USE: For pin worm, round worm & hook worm Oxantel pamoate (1dose) for Trichuriasis MOA: Depolarizing neuromuscular blockers, induce marked persistent activation of nicotinic (Ach) receptors of worm; open the cationic channels resulting in irreversible, spastic paralysis of worm; it also inhibits cholinesterases Low absorption (>85% passes in feces unaltered) Safe for pregnant woman

3. Ivermectin (Nippon Y. Zasshi, 2003 & Gyatt H, De S 3. Ivermectin (Nippon Y. Zasshi, 2003 & Gyatt H, De S. N Bundy,1997 May) A semisynthetic anthelmintic MOA: Binds selectively and with strong affinity to GABA or glutamate-gated chloride ion channels in invertebrate nerve and muscle cells Binding leads to Hyperpolarization of cell membrane due to influx of chloride ions (glutamate) due to GABA (direct release) & its receptor stimulation Result: Paralysis of muscles & death of parasite

Ivermectin 93% plasma protein-bounded Excretion via GI route only Poor CSF distribution P-glycoprotein efflux pump Resistance: Widespread use in sheep & cattle

Ivermectin Uses Strongyloidiasis Elephantiasis (mass treatment) Onchocercus volvulus (DOC) Cutaneous larva migrans Scabies

Ivermectin Adverse effects: not much; minimal in absence of parasitic infection In filariasis: Fever, myalgia, lightheadedness, malaise & postural hypotension Mazotti reaction in heavy infection due to dying microfilariae In onchocerciasis: Skin edema, pruritus & mild eye irritation, headache, dizziness, abdominal pain In combine onchocerciasis & heavy Loa-loa infection: Encephalopathy, do not use) Don’t use in trypanosomiasis or meningitis

4. Diethylcarbamazine Piperazine derivative DOC for lymphatic filariasis (adult of W. bancrofti, Brugia malayi & loasis (best for loasis), tropical pulmonary eosinophilia of W. bancrofti and B. malayi, can be used in visceral larva migrans MOA: Arachidonic acid metabolism interference Adjust dose in renal dysfunction Mazotti reaction in onchocerciasis

5. Praziquantel Treatment of cestodes & trematodes Increases Ca++ influx in tegumental cells causing tetanic contracture & loss of adherence to host’s tissue Food & cimetidine facilitate absorption; Extensive first pass metabolism Anticonvulsants in cysticercosis & spasmolytic in abdominal pain

The End