Anthelmintic Drugs

Three major groups of helminths infect man:

Nematodes
Ivermetin, mebendazole, albendazole,
pyrantel pamoate, thiabendazole

Trematodes (flukes)
Praziquantel

Cestodes
Niclosamide
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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

Life cycle of Ascaris lumbricoides

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.

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: 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)
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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 helminths 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 parasites
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 parasites mitochondrial
anaerobic phosphorylation of ADP to ATP.
The drug is lethal to the cestodes 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 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 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)

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