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)