ANTHELMINTIC DRUGS Helminth Infections 1 Tapeworms cestodes Beef

ANTHELMINTIC DRUGS Helminth Infections 1 -Tapeworms ( cestodes) Beef tapeworm / fish tapeworm 2 - Intestinal round worms ( nematodes) Ascaris, pinworm , whipworm, strongyloides, ancylostoma ( hookworm ). A skin infection is termed cutaneous larva migrans Visceral larva migrans.

Anthelminthic Drugs o May act by causing : o 1 - paralysis of the worm. o 2 - damaging the worm leading to partial digestion or rejection by immune mechanisms. o 3 - interfere with the metabolism of the worm. *Worms or larvae live in tissues of host body like muscles , viscera , menninges , subcutaneous tissues.

o Adult filariae live in the lymphatics, connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream. o They are ingested by mosquitoes or similar insects, they develop to larvae in 2 ndry host and pass to mouth parts of insect and re-injected to humans

Ascaris lumbricoids ( common round worm)

filariasis

Hookworm

Pinworm male , female

Tapeworm

whipworm

Dircrocoelium dendriticum

Fasiola hepatica

Tricuris tricura

Trichinela spiralis

elephantiasis

Hydateid cyct

cysticercosis

ANTHELMINTIC DRUGS ALBENDAZOLE o Broad spectrum oral anthelmintic o Drug of choice for treatment of hydatid disease and cysticercosis, it is also used for the treatment of ascariasis , tricurasis and strongyloidiasis, pinworm, hookworm

Mechanism Of Action o Inhibits microtubule synthesis by binding to β –tubulin. o Inhibits mitochondrial reductase causing reduced glucose transport. . Intestinal parasites are immobilized and die slowly. o larvicidal in hydatid , cysticercosis , ascariasis and hook worm infections. o Ovicidal in ascariasis , hookworm , trichuriasis

Pharmacokinetics o Benzimidazole carbamate o Administered orally , absorption increased with a fatty meal o Metabolized in the liver to the active metabolite albendazole sulfoxide

Pharmacokinetics o Plasma half life is 8 -12 hours o sulfoxide is mostly protein bound distributes well to tissues and enters bile, CSF & hydatid cysts. o Metabolites are excreted in urine

Clinical uses o Used on empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites. o In ascariasis , trichuriasis , hookworm, pin worm infections : children over 2 years & adults (single dose 400 mg, repeated for 2 -3 day in heavy ascaris infection. For 2 wks for pin worm infection 2. Hydatid diseases: drug of choice for medical therapy& adjunctive to surgical removal or aspiration of cysts.

Albendazole (con’) 3. Neurocysticercosis: Used with corticosteroid to decrease the inflammation caused by dying organism and it also reduces the duration of course for 21 days 4. Other infections: Drug of choice in cutaneous and visceral larva migrans , intestinal capillariasis, giardiasis & taeniasis.

Adverse Effects o In short term(1 -3 days): Mild epigastric pain, diarrhea, nausea, headache & insomnia. o In long term use : for hydatid cyst and cysticercosis : abdominal pain, headache , fever , fatigue, alopecia , increased liver enzymes , pancytopenia. Blood counts and liver enzymes should be followed. o Not given during pregnancy, hypersensitive people to benzimidazole drugs & children under 2 years.

MEBENDAZOLE (Vermox) o Synthetic benzimidazole o Wide spectrum and low incidence of adverse effects Mechanism of action: Inhibits microtubule synthesis. It kills hookworm, pin worm , ascaris and trichuris eggs.

Pharmacokinetics less than 10% of orally administered drug is absorbed o Absorption increases with fatty meal. o Absorbed drug is 90 % protein bound o Converted to inactive metabolites. o Half- life of 2 -6 hours o Excreted mostly in urine.

Clinical Uses It is taken orally before or after meal , tablets should be chewed before swallowing. o Pinworm , trichuriasis, hookworm & ascaris infections. o in adults and children over 2 years cure rate is 90 -100 % except hookworm it is less.

Adverse Effects & Precautions o Short term therapy. Mild GI disturbance. o High dose : hypersensitivity reactions, agranulocytosis , alopecia , elevation of liver enzymes. Used with caution under 2 ys of age may cause convulsion. Contraindicated in pregnancy. o Enzyme inducers and inhibitors affect plasma level of the drug.

Thiabendazole o Benzimidazole o Chelating agent and form stable complexes with metals including iron, but does not bind with calcium. o Rapidly absorbed o Half- life of 1 -2 hrs o Completely metabolized in liver and 90% is excreted in urine o Can also absorbed through skin

Mechanism Of Action o Similar to other benzimidazoles. It is ovicidal for some parasites o Clinical uses: o Should be given after meals. and tablets should be chewed o Strongyloidal infections & cutaneous larva migrans. Thiabendazole cream is applied topically or drug can be given orally for 2 days.

Adverse Effects & Contraindications o More toxic than other benzamidazoles o GI disturbances o Pruritus , headache, drowsiness , psychoneurotic symptoms. o Irreversible liver failure. o Fatal Stevens –Johnson syndrome o Not used in young children , pregnancy, hepatic and renal diseases.

PYRANTEL PAMOATE o o Broad spectrum Pharmacokinetics: Poorly absorbed from GIT Half of the drug is excreted unchanged in the feces. o Mechanism of action: o result in paralysis of worms. It is a neuromuscular blocking agent Efficacy o Very effective against luminal organisms( mature or immature forms). o Not effective against migratory stages in the tissues or against ova

Clinical uses Pin worm given orally with or without food. o Ascariasis o Hookworm

Adverse Effects o Infrequent mild transient GI disturbance o drowsiness , headache , insomnia. o Rash , fever Contraindications & Cautions o Should be used with caution in liver dysfunction. o Pregnancy o Children under 2 years of age

PIPERAZINE o Only recommended for the treatment of ascariasis cure rate 90% for 2 days treatment. o Readily absorbed orally and excreted mostly unchanged in urine o Mechanism of action: Causes paralysis of ascaris by blocking acetylcholine at myoneural junction , the live worms expelled by normal peristalsis.

o Treatment is continued for 3 -4 days or repeated after one week in case of heavy infections.

Adverse Effects o o o o GI disturbance Neurotoxicity , allergic reactions. Contraindications Epilepsy or a history of epilepsy Impaired liver or kidney functions pregnancy Chronic neurologic disease

NICLOSAMIDE o Second-line drug for treatment of most tapeworm infections. o Mechanism of action: o Adult worm( not ova) is rapidly killed by inhibition of oxidative phosphorylation. o Pharmacokinetics: o Poorly absorbed from gut & excreted in urine.

Clinical Uses o Treatment of most forms of tapeworms. o Not effective against cysticercosis or hydatic disease. o Given in the morning on empty stomach. o Purgative is necessary to purge all dead segments& prevent liberation of ova.

Adverse effects & Contraindications o Mild , infrequent and transitory GI disturbance o Alcohol consumption should be avoided o Not indicated in children under 2 years of age or in pregnancy.

DIETHYL CARBAMAZINE o Drug of choice for the treatment of filariasis and tropical eosinophilia. o Pharmacokinetics: o Rapidly absorbed from gut o Half- life is 2 -3 hours o The drug should be given after meals o It is excreted in urine as unchanged or metabolite. o Dosage is reduced in urinary alkalosis and renal impairment.

Mechanism Of Action o Immobilizes microfilariae and alters their surface structure , displacing them from tissues & making them susceptible to destruction by host defense mechanism o It has immunosuppressive effects

Adverse Effects o Fever , malaise, papular rash, headache, GI disturbance, cough. Chest, muscle, joint pain o Leucocytosis o Retinal hemorrhage o Encephalopathy o lymphangitis and lymphadenopathy. o *It is not teratogenic

Contraindications & Cautions o * Hypertension o* Renal disease *patient with lymphangitis

IVERMECTIN o o o o Drug of choice for treatment of strongyloidiasis Macrocyclic lactone ring Given only orally Rapidly absorbed Does not cross BBB. Half- life is 16 hrs Excretion is mainly in feces.

Mechanism Of Action Acts on the parasitte, s glutamategated Cl- channel receptors. Chloride influx increased , hyperpolarization occurs , resulting in paralysis of the worm. Or o Paralyze nematodes by intensifying GABA- mediated transmission of signals in peripheral nerves. o

Clinical uses o Drug of choice for cutaneous larva migrans & strongyloidiasis. o Onchocerciasis o It is also used for scabies , lice. o Filariasis.

Adverse Effects o Fatigue , dizziness, GI disturbance o Killing of microfilaria result in a Mazotti reaction ( fever, headache, dizziness, somnolence, hypotension , tachycardia, peripheral edema……). o Corneal opacities & other eye lesions.

Contraindications & Cautions o Concomitant use with other drugs that enhance GABA e. g Barbiturates, bnzodiazepines, valproic acid. o pregnancy o Meningitis o Children under 5 years of age.

BITHIONOL o Drug of choice for the treatment of fascioliasis ( sheep liver fluke) o Pharmacokinetics: o It is orally administered and excreted in urine.

Adverse Effects o GI disturbance ( N. , V. , D. , A. ) Dizziness, headache Skin rashes , urticaria, Leucopenia o Contraindications and precautions: Hepatitis , leucopenia Used with caution in children under 8 years of age.