ANTHELMINTIC DRUGS

Anthelminthic DrugsMay act by causing :

Paralysis of the worm.

Damaging the worm leading to partial digestion or

rejection by immune mechanisms.

Interfere with the metabolism of the worm.

*Worms or larvae live in tissues of host body like muscles,

viscera, meninges, 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 2o 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 DRUGSM-mebendazole A-albendazoleN-niclosamideI-ivermectinP-praziquantel A-albendazoleL-levamisole P- pyrental pamoateD-diethylcarbamazine mnemonic:MANIPAL PD

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 yrs & 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.

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 yrs 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 2yrs 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

MOA: Causes paralysis of ascaris by blocking Ach 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 yrs 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 C/I: 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 parasites 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)

PK: It is orally administered and excreted in urine.A/E:GI disturbance ( N., V., D., A.)

Dizziness, headache Skin rashes, urticaria, Leucopenia

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