ANTHELMINTIC DRUGSHelminth Infections

1-Tapeworms ( cestodes) Beef tapeworm / fish tapeworm2- Intestinal round worms ( nematodes)Ascaris, pinworm ,whipworm, strongyloides, ancylostoma ( hookworm ).A skin infection is termed cutaneous larva migrans

Visceral larva migrans .

Anthelminthic Drugs May act by causing : 1- paralysis of the worm. 2- damaging the worm leading to partial digestion

or rejection by immune mechanisms. 3- interfere with the metabolism of the worm.

*Worms or larvae live in tissues of host

body like muscles , viscera , menninges ,

subcutaneous tissues.

Adult filariae live in the lymphatics, connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream.

They are ingested by mosquitoes or similar insects, they develop to larvae in 2ndry 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 Broad spectrum oral anthelmintic 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

Inhibits microtubule synthesis by binding to β –tubulin.

Inhibits mitochondrial reductase causing reduced glucose transport.. Intestinal parasites are immobilized and die slowly.

larvicidal in hydatid ,cysticercosis , ascariasis and hook worm infections.

Ovicidal in ascariasis ,hookworm , trichuriasis

Pharmacokinetics

Benzimidazole carbamate

Administered orally , absorption increased with a fatty meal

Metabolized in the liver to the active metabolite albendazole sulfoxide

Pharmacokinetics

Plasma half life is 8-12 hours sulfoxide is mostly protein bound

distributes well to tissues and enters bile,CSF & hydatid cysts.

Metabolites are excreted in urine

Clinical uses

Used on empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites.

In ascariasis ,trichuriasis ,hookworm, pin worm infections : children over 2 years & adults (single dose 400mg, 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

In short term(1-3 days): Mild epigastric

pain,diarrhea, nausea, headache & insomnia.

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.

Not given during pregnancy, hypersensitive people to benzimidazole drugs & children under 2 years .

MEBENDAZOLE (Vermox)

Synthetic benzimidazole 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

Absorption increases with fatty meal. Absorbed drug is 90 % protein bound Converted to inactive metabolites . Half- life of 2-6 hours Excreted mostly in urine .

Clinical Uses

It is taken orally before or after meal , tablets should be chewed before swallowing.

Pinworm , trichuriasis, hookworm & ascaris infections.

in adults and children over 2 years cure rate is 90-100 % except hookworm it is less.

Adverse Effects & Precautions

Short term therapy.Mild GI disturbance.

High dose : hypersensitivity reactions, agranulocytosis , alopecia ,elevation of liver enzymes .

Used with caution under 2ys of age may cause convulsion. Contraindicated in pregnancy.

Enzyme inducers and inhibitors affect plasma level of the drug.

Thiabendazole Benzimidazole

Chelating agent and form stable complexes with metals including iron, but does not bind with calcium.

Rapidly absorbed

Half- life of 1-2 hrs

Completely metabolized in liver and 90% is excreted in urine

Can also absorbed through skin

Mechanism Of Action

Similar to other benzimidazoles. It is ovicidal for some parasites

Clinical uses: Should be given after meals .and tablets should be

chewed

Strongyloidal infections & cutaneous larva migrans .Thiabendazole cream is applied topically or drug can be given orally for 2 days.

Adverse Effects & Contraindications

More toxic than other benzamidazoles GI disturbances Pruritus ,headache, drowsiness ,

psychoneurotic symptoms. Irreversible liver failure. Fatal Stevens –Johnson syndrome Not used in young children , pregnancy, hepatic

and renal diseases.

PYRANTEL PAMOATE Broad spectrum Pharmacokinetics: Poorly absorbed from GIT Half of the drug is excreted unchanged in the feces. Mechanism of action: result in paralysis of worms. It is a neuromuscular blocking

agent Efficacy

Very effective against luminal organisms( mature or immature forms).

Not effective against migratory stages in the tissues or against ova

Clinical uses

Pin worm given orally with or without food.

Ascariasis

Hookworm

Adverse Effects

Infrequent mild transient GI disturbance drowsiness , headache ,insomnia. Rash ,fever

Contraindications & Cautions Should be used with caution in liver dysfunction. Pregnancy Children under 2 years of age

PIPERAZINE Only recommended for the treatment

of ascariasis cure rate 90% for 2 days treatment.

Readily absorbed orally and excreted mostly unchanged in urine

Mechanism of action: Causes paralysis of ascaris by blocking

acetylcholine at myoneural junction , the live worms expelled by normal peristalsis.

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

Adverse Effects

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

NICLOSAMIDE

Second-line drug for treatment of most tapeworm infections.

Mechanism of action: Adult worm( not ova) is rapidly killed by

inhibition of oxidative phosphorylation . Pharmacokinetics: Poorly absorbed from gut & excreted in urine.

Clinical Uses

Treatment of most forms of tapeworms. Not effective against cysticercosis or hydatic

disease. Given in the morning on empty stomach. Purgative is necessary to purge all dead segments&

prevent liberation of ova.

Adverse effects & Contraindications

Mild ,infrequent and transitory GI disturbance

Alcohol consumption should be avoided

Not indicated in children under 2 years of age or in pregnancy.

DIETHYL CARBAMAZINE Drug of choice for the treatment of filariasis and

tropical eosinophilia. Pharmacokinetics: Rapidly absorbed from gut Half- life is 2-3 hours The drug should be given after meals It is excreted in urine as unchanged or metabolite. Dosage is reduced in urinary alkalosis and renal

impairment.

Mechanism Of Action

Immobilizes microfilariae and alters their surface structure ,displacing them from tissues & making them susceptible to destruction by host defense mechanism

It has immunosuppressive effects

Adverse Effects

Fever , malaise, papular rash, headache, GI disturbance,cough. Chest,muscle,joint pain

Leucocytosis Retinal hemorrhage Encephalopathy lymphangitis and lymphadenopathy. *It is not teratogenic

Contraindications & Cautions

* Hypertension

* Renal disease

*patient with lymphangitis

IVERMECTIN 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 glutamate-gated Cl- channel receptors . Chloride influx increased , hyperpolarization occurs , resulting in paralysis of the worm. Or

Paralyze nematodes by intensifying GABA- mediated transmission of signals in peripheral nerves.

Clinical uses Drug of choice for cutaneous larva

migrans & strongyloidiasis. Onchocerciasis

It is also used for scabies , lice . Filariasis.

Adverse Effects

Fatigue ,dizziness, GI disturbance Killing of microfilaria result in a Mazotti

reaction ( fever, headache, dizziness, somnolence, hypotension , tachycardia, peripheral edema……).

Corneal opacities & other eye lesions.

Contraindications & Cautions

Concomitant use with other drugs that enhance GABA

e.g Barbiturates, bnzodiazepines, valproic acid. pregnancy Meningitis Children under 5 years of age.

BITHIONOL

Drug of choice for the treatment of fascioliasis ( sheep liver fluke)

Pharmacokinetics: It is orally administered and excreted in urine.

Adverse Effects

GI disturbance ( N., V., D., A.) Dizziness, headache Skin rashes , urticaria, Leucopenia

Contraindications and precautions: Hepatitis , leucopeniaUsed with caution in children under 8 years of age.