anthelminthic n.
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Anthelminthic

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

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

  3. Commonly encounterdtrematodeinfections • Schistosomiasis

  4. Commonly encounterdcestodeinfections • Echinococosis (hydatid disease). • Taeniasis • Cysticercosis

  5. Drugs • Benz-imidazolesMebendazoleAlbendazoleThiabendazole • Pyrantelpamoate / Oxantelpamoate • Ivermectin • Diethylcarbamazine (table salt) • Praziquantel

  6. 1. Benzimidazole: Mebendazole Mechanism Of Action: • Inhibits polymerization of tubulin protein by binding to β-tubulin of intestinal & tegumental cells of worm(The tegmentum (from Latin for "covering") is a general area within the brainstem.;) • also inhibits fumaratereductase • Loss of cytoplasmic microtubules leads to up-take of microtubule dependent glucose & depletion of glycogen stores; no glucose no ATP; oxidation-phosphorylation in mitochondria • Result: No energy, no mobility, death of worm • (*polymerization is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks)*.

  7. 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

  8. USES: • Effective against 4 nematodes like, Pin, Round, Whip and hook worms (both variety) • For all these four types remember the DOC is mebendazole; with some exceptions

  9. Now we want to know what these names, pin, round, whip and hooks are like. 1. Remember you can collect these pins on one sticky tape (associate it with children who are afraid of pins and needles and these vermicelli are as thin as pins and needles) 2. Now round is your ball Ascarislumbricoides’ ball formation causing intestinal obstruction 3. Whip is TRICky (Trichiuristrichuria) and shapes just like the whip you use to make the horse run fast 4. Hooks are usually two; Necatoramericanus (nectar of flowers is sucked by insects) and Ancylostomaduodenale are hooked to intestinal wall to suck the blood

  10. 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

  11. 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

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

  13. Ivermectin Uses • Strongyloidiasis (due to Nematodes ) • Elephantiasis (mass treatment) Elephantiasis is a disease that is characterized by the thickening of the skin and underlying tissues, especially in the legs, male genitals. • Onchocercus volvulus (DOC-Tropical disease of skin & underlying connective tissue) • Cutaneous larva migrans • Scabies

  14. 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 (*A severe, potentially life-threatening allergic response that occurs within seven days of treatment of microfilariasis *) • In onchocerciasis: Skin edema, pruritus & mild eye irritation, headache, dizziness, abdomina pain • In combine onchocerciasis & heavy Loa-loa infection: Encephalopathy (Pion SD 2006),so do not use) • Don’t use in trypanosomiasis or meningitis

  15. 4. Diethylcarbamazine • Piperazine derivative • DOC for lymphatic filariasis (adult of W. bancrofti, B. malayi & 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

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

  17. The End