Anthelmintic Drugs. Helmintic infections Human is the primary host for most helminthic infections. ...

Anthelmintic Drugs

Helmintic infections

Helmintic infections

Human is the primary host for most helminthic infections.

Most worms produce eggs and larva

These pass out of human body and infect secondary host

Immature forms invade humans via skin or GIT

Types of worms

Worms live in host,s alimentary canal

Worms or larvae live in muscles , viscera , menninges, lungs. Subcutaneous tissues

Intestinal Worms

A) Round worms ( Nematodes )

Ascaris lmubricods ( common ) Enterobius vermicularis ( pin worm) Trichris trichuria ( whip worm) Strongyloids stercoralis ( thread Ankylostoma dudenale ( hook worm

B) Tape worms ( cestodes )

Taenia saginata ( Beef) Taenia solium ( pork) Humans become infected by eating

raw or unde cooked meat containing larvae of infected cattle or pig

Continue ( cestodes )

In some cases the larva gets encysted in muscles , viscera , brain , eye resulting in cysticercosis

Tissue worms

Filariae ( bancrofti, loa loa ) Adult filariae live in the lymphatics ,

causing lymphadenitis , swelling of limb. Microfilariae goes to blood stream to be ingested by mosquitoes

Trichnella spiralis : larva migrats from intestine to tissues of leg or foot producing ulcer

Anthelminthic Drugs

May 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.

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 Drug of choice for treatment of hydatid

disease and cysticercosis. Used for the treatment of ( intestinal

nematodes ) e.g. ascariasis , tricurasis and strongyloidiasis, pinworm, hookworm

Mechanism Of Action

Inhibits microtubule synthesis that irreversibly impairs glucose uptake , 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 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

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 & others

Adverse Effects

In short term(1-3 days): No significant adverse

effects

In long term use : abdominal pain, headache ,fever ,fatigue, alopecia ,

increased liver enzymes , pancytopenia. Not given during pregnancy, hypersensitive peoples &

children under 2 years .

MEBENDAZOLE (Vermox)

Synthetic benzimidazole Wide spectrum and safer than albendazole

Mechanism of action:

As albendazole

It kills hookworm, pin worm , ascariasis 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 in urine .

Clinical Uses

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.

.

Thiabendazole Mechanism as other 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

Clinical uses

Should be given after meals .and tablets should be chewed

Strongyloidal infections In 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 PAMOATEBroad spectrum Pharmacokinetics: Poorly absorbed orally Half of the drug is excreted unchanged in the feces.Mechanism of action: Neuromuscular blocking drug leads to paralizes of worms

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 GI disturbance drowsiness , headache ,insomnia. Rash ,fever

Contraindications 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 Impaired liver or kidney functions pregnancy

NICLOSAMIDE

Second-line drug for treatment of tape worm infections.

Mechanism of action: Adult worm 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

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

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

Patients suspected of malaria

IVERMECTIN Drug of choice for treatment of filaria &

strongyloidiasis It is a macrocyclic lactone ring Given only orally Rapidly absorbed Does not cross BBB. Half- life is 16 hrs Excretion in urine & feces.

Mechanism Of Action

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 ( it is microfilaricidal ).

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 Dizziness, headache Skin rashes , urticaria, Leucopenia

Contraindications and precautions: Hepatitis , leucopenia Used with caution in children under 8 years

of age.