Anthelmintic Drugs

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Anthelmintic DrugsThree major groups of helminths infect man:Nematodes

Ivermetin, mebendazole, albendazole, pyrantel pamoate, thiabendazole

Trematodes (flukes)Praziquantel

CestodesNiclosamide

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Helminths • Nematodes- elongated roundworms,• Have complete digestive system (with

mouth and anus),• Cause infections of

– Small intestine (e.g. Ascaris species), – Blood/lymph (e.g. Wuchereria bancrofti -

filariasis) – Tissues (e.g. Trichinella spiralis).

• Drugs: mebendazole, albendazole, pyrantel pamoate, thiabendazole, Ivermetin

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Life cycle of Ascaris lumbricoides

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Nematodes • Adult worms (1) live in the lumen of the small intestine.

A female may produce up to 240,000 eggs per day, which are passed with the feces 

• (2) Fertile eggs embryonate and • (3) become infective after 18 days to several weeks

depending on the environmental conditions (optimum: moist, warm, shaded soil).

• (4) After infective eggs are swallowed the larvae hatch 

• (5) invade the intestinal mucosa, and • (6) are carried via the portal, then systemic circulation

to the lungs .

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• (7) The larvae mature further in the lungs (10-14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed.

• Upon reaching the small intestine, they develop into adult worms (1).

• Between 2 and 3 months are required from ingestion of the infective eggs to oviposition by the adult female.

• Adult worms can live 1 to 2 years. 

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Symptoms/Pathology

• Infection with Ascaris lumbricoides often causes no symptoms. 

• But large number of worms may cause abdominal pain or intestinal obstruction. 

• Adults feed on the contents of the small intestine and heavy infections may compound problems in malnourished individuals (especially children). 

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• Migration of larvae may cause localized reactions in various organs. 

• Penetration of the larvae from capillaries into the lungs can lead to Loeffler's pneumonia, (pools of blood and dead epithelial cells clog air spaces in the lungs). 

• Resulting bacterial infections can be fatal.

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• Trematodes (flukes)- leaf-shaped flatworms,– Are generally characterized by the tissues

they infect, eg liver, lung, intestinal, or blood flukes (e.g. Schistosoma species).

Drug: PraziquantelCestodes – have flat, segmented body

they attach to the host’s intestine,no digestive tract in their life cycle (Taenia spp).

Drug: Niclosamide

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Ivermetin – Drug of choice for onchocerciasis– Alternative drug in Wuchereria spp, Brugia

spp, Loa loa infections (filariasis)– It interacts with chloride channel on the

helminth GABA receptors. – This causes chloride influx leading to

hyperpolarization, which paralysis the worm. – The immune system then recognize the

paralyzed microfilariae as a foreign antigen.– It also reduces the capacity of the adult

female O. volvulus to produce microfilariae*. (*Mechanism for this action is not known)

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Ivermectin II– Given orally; adults 150 mcg per kg body

weight, as a single dose. Repeat in 3 to 12 months.

– Does not cross the blood brain barrier

• Side effects: intense pruritus, papular rash, swelling of inguinal lymph nodes and optic nerve atrophy.

• Diethylcarbamazine has similar but more serious side effects).

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Mebendazole

• Synthetic benzimidazole compound.• Has a broad spectrum of activity against

nematodes.• Drug of choice for

– whipworm (Trichuris trichiura),– Pinworm (Enterobius vermicularis),– Hookworm (Necator americanus &

Ancylostoma duodenale)– Roundworm (Ascarisis lumbricoides)

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Mebendazole II

Mechanism of action– It inhibits the polymerization of the parasite

tubulin into microtubules.– Loss of cytoplasmic microtubules leads to

impaired uptake of glucose by larval & adult parasites.

– Results in loss of energy immobilization death.

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Albendazole • Is a benzimidazole compound, with a broad

spectrum of action on helminths• Active against: whipworm, hookworm,

roundworm, pinworm, • Also active against

– threadworm (Strongyloides stercoralis), – tapeworm (Taenia spp), *Albendazole 400mg is combined with

diethylcarbamazine to treat lymphatic elephantiasis• Mech. of action is similar to that of mebendazole.

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Thiabendazole • Synthetic benzimidazole derivative• Effective against

– Strongyloides stercorales, – cutaneous larva migrants – Trichinella spiralis– It also affects microtubular aggregation like the other

benzimidazoles.– In addition, thiabendazole seem to inhibit a helminth

enzyme, fumarate reductase, in the citric acid cycle– This thereby interfere with the helminth’s source of

energy.

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Thiabendazole II

• Readily absorbed on oral administration

Adverse effects• GIT disturbances, • Headache, dizziness, drowsiness• Allergic reactions (fever, rash)

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Pyrantel pamoate• Effective against roundworm, pinworm, and

hookworm.• Poorly absorbed from the git• It targets the nervous system of the helminth;

– It acts as a depolarizing neuromuscular blocking agent, causing persistent activation of parasite’s nicotinic receptors.

– Paralyzed worm is expelled from host intestinal tract.

• Adverse effects: GIT upsets, fever, dizziness

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Niclosamide

• Is the drug of choice for cestode (tapeworm) infections.

• It inhibits the parasite’s mitochondrial anaerobic phosphorylation of ADP to ATP.

• The drug is lethal to the cestode’s scolex and segments but not the ova.

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Niclosamide II

• Advisable to administer a laxative prior to oral administration of niclosamide.

• Dose; adult 2g after a light breakfast,

• Side effect: GIT discomfort.

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Praziquantel

• An acylated quinoline-pyrazine. • Indicated for treatment of schistosomiasis• It has a broad spectrum of activity against

trematodes (blood flukes) and cestodes (tapeworms).

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Praziquantel II

• It increases the permeability of the worm’s cell membrane to calcium ions;

• This causes massive contraction and paralysis of its musculature and disintegration of worm’s tegumental layer.

• The disintegration of the tegumental layer activates the host’s defense mechanisms; this results in destruction of the worms.

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Praziquantel III

• It is given orally; 40 mg/kg body weight as single dose for both adult and children.

• Adverse reactions: nausea, abdominal pain, headache, sedation, fever, sweating.

• Interaction: increase praz metabolism have been reported with dexamethasone, phenytoin & carbamazepine.

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Praziquantel IV

• Cimetidine increases praziquantel levels in blood.

• Contraindicated in treatment of ocular cysticercosis

• Since destruction of the organism in the eye may damage the organ.

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Diethylcarbamazine

• Treatment of filariasis• Highly effective against

– microfilariae and adults of Loa loa, Wuchereria bancrofti,

– microfilariae of Onchocerca volvulus. (suramin is active against the adult worm)

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Diethylcarbamazine II

• It kills microfilaria;– possibly by altering the parasite surface

membrane and thus activating the host immune system.

– there is a decrease activity and subsequent paralysis of the worm.

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Diethylcarbamazine III

• A single dose of Diethylcarbamazine (3mg/kg body wt) + albendazole (400mg) given concurrently

• New treatment for lymphatic elephantiasis (Wuchereria bancrofti infection)