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

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

Commonly encounterd trematode infections Schistosomiasis

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

Drugs Benz-imidazoles 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(The tegmentum (from Latin for "covering") is a general area within the brainstem.;) also inhibits fumarate reductase 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)*.

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

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 Ascaris lumbricoides’ ball formation causing intestinal obstruction 3. Whip is TRICky (Trichiuris trichuria) and shapes just like the whip you use to make the horse run fast 4. Hooks are usually two; Necator americanus (nectar of flowers is sucked by insects) and Ancylostoma duodenale are hooked to intestinal wall to suck the blood

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 (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

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 (*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

4. Diethylcarbamazine Piperazine derivative DOC for lymphatic filariasis (adult of W. bancrofti, B. 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’ tissue Food & cimetidine increases the absorption; Extensive first pass metabolism Anticonvulsants in cysticercosis & spasmolytic in abdominal pain

The End