Anthelminthic

Kaukab Azim, MBBS, PhDModified 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: 1. Inhibits polymerization of tubulin protein by

binding to β-tubulin of intestinal & tegumental cells of worm

2. 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. 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