Anthelminthic

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

2. Commonly encountered nematode (roundworm) infections • Onchocerciasis (river blindness) • Enterobiasis (pinworm) • Ascariasis(roundworm) • Filariasis • Trichuriasis (whipworm disease ) • Hookworm (ancylostomaduodanale) • Strongyloidiasis (threadworm)

5. Commonly encounterdtrematode (Flukes) infections • Schistosomiasis

6. Commonly encounterdcestode (Tapeworms) infections • Echinococosis (hydatid disease). • Taeniasis • Cysticercosis

8. Drugs • BenzimidazolesMebendazoleAlbendazoleThiabendazole • Pyrantelpamoate / Oxantelpamoate • Ivermectin • Diethylcarbamazine (table salt) • Praziquantel

9. 1. Benzimidazole: Mebendazole Mechanism Of Action: • Inhibits polymerization of tubulin protein by binding to β-tubulin of intestinal & tegumental cells of worm • Also inhibits fumaratereductaseimportant 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

10. 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 (Necatoramericanusand Ancylostomaduodenale)

11. 2. PyrantelPamoate • USE: • For pin worm, round worm & hook worm • Oxantelpamoate (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

12. 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

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

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

16. Ivermectin • Adverse effects: not much; minimal in absence of parasitic infection • In filariasis: Fever, myalgia, lightheadedness, malaise & postural hypotension • Mazotti reactionin 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

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

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

19. The End