Anthelmintic Drugs

Three major groups of helminths infect man:

NematodesIvermetin, 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 (eg Ascaris species),
Blood/lymph (eg Wuchereria bancrofti filariasis) and
tissues (eg Trichinella spiralis).

Drugs: mebendazole, albendazole,

pyrantel pamoate, thiabendazole,
Ivermetin

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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Life cycle of Ascaris lumbricoides

 (7) The larvae mature further in the lungs (1014 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.

 Trematodes (flukes)- leaf-shaped flatworms,

Are generally characterized by the tissues they
infect, eg liver, lung, intestinal, or blood flukes
(eg. Schistosoma species).
watch animation!

Drug: praziquantel
Cestodes have flat, segmented body
they attach to the hosts 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)

Ivermectin (2)
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 (1)

a 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 (2)
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.
this results in loss of energy immobilization
death.

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Albendazole (1)
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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Thiabemdazole (1)
Synthetic benzimidazole derivative
Effective against
Strongyloides stercorales,
cutaneous larva migrants and
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 helminths source if
energy.
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Thiabendazole (2)
Readily absorbed on oral administration
Adverse effects---- BNF

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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 parasites
nicotinic receptors.
Paralyzed worm is expelled from host intestinal
tract.

Adverse effects---consult BNF.

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Niclosamide (1)
Is the drug of choice for cestode
(tapeworm) infections.
In its action, it inhibit the parasites
mitochondrial anaerobic phosphorulation
of ADP to ATP.
The drug is lethal to the cestodes scolex
and segments but not the ova.

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Niclosamide (2)
Hence, 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 (1)

(use in schistosomiasis)

is an acylated quinoline- pyrazine.

It has a broad spectrum of activity against
trematodes (blood flukes) and cestodes
(tapeworms).

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Praziquantel (2)
It increases the permeability of the worms
cell membrane to calcium ions;
this causes massive contraction and
paralysis of its musculature and
disintegration of worms tegumental layer.
The disintegration of the tegumental layer
activates the hosts defense mechanisms;
this results in destruction of the worms.
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Praziquantel (3)
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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Praz. (4)
Cimetidine increases praz 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 (DEC) in filariasis

Highly effective against
microfilariae and adults of Loa loa,
Wuchereria bancrofti,
microfilariae of O. volvulus. (suramin is active
against the adult worm)

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DEC (2)
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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DEC (3)
A single dose of
DEC (3mg/kg body wt) + albendazole
(400mg)
given concurrently,
is the new treatment for
lymphatic elephantiasis (W. bancrofti infection)

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