University of Medical Sciences

ONDO
Anthelmintic Drugs
Dr. M.S. Fageyinbo
 Introduction
• Infection by helminths (worms) may be limited solely to the

intestinal lumen

or may:

• involve a complex process with migration of the adult or

immature worm through the body before localization in a

particular tissue.
• Treatment may complicated by infection with more

than one genus of helminth

• Pathogenic helminths can be divided into the

following major groups:

 Nematodes

• Round worm (Ascaris lumbricoides)

• Hook worm (Necator americanus and Ancylostoma duodenale)

• Pinworm (Enterobius vermicularis)

• Threadworm (Strongyloides stercoralis)

• Filarial worm (Wuchereria bancrofti and Brugia malayi, Onchocerca

volvulus)

• Whip worm (Trichuris trichiura)

• Trichinea worm (Trichinella spiralis)

• Guinea worm (Dracunculus medinensis)

Trematodes

• Blood fluke (Schistosoma haematobium, mansoni

and japonicum)

• Lung fluke (Paragonimus westermani)

• Liver fluke (Fasciola hepatica)

Cestodes

• Pork tapeworm (Taenia solium)

• Beef tapeworm (Taenia saginata)

• Fish tapeworm (Diphyllobothrium latum)

• Dog tapeworm (Echinococcus granulosus)

• Dwarf tapeworm (Hymenolepis nana)

• Most available anthelmintic drugs exert their
antiparasitic effects by interference with
(1) energy metabolism,
(2) neuromuscular coordination,
(3) microtubular function, and
(4) cellular permeability.
Classification
• Based on mechanism of action, these drugs may be
classified as:
 Drugs inhibiting polymerization of beta tubulin:
Albendazole, mebendazole, thiabendazole, triclabendazole
 Drugs causing spastic paralysis (NN receptor agonist):
Pyrantel pamoate, levamisole

 Drugs causing flaccid paralysis (GABAA agonist):

Piperazine, ivermectin
 Drugs altering microfilarial membrane and increasing

phagocytosis: Diethylcarbamazine (DEC)

 Drugs causing uncoupling of oxidative

phosphorylation: Bithionol, niclosamide

 Drugs causing influx of calcium: Praziquantal.

 Mode of Action of Drugs Employed in
Chemotherapy of Helminthic Diseases
• Piperazine: Paralyzes helminth muscle; Blocks myoneural
junction; causes chloride-dependent hyperpolarization,
flaccid paralysis
• Ivermectin: Paralyzes helminth muscle Blocks transmission
of nerve signals by interactions with glutamate-gated
chloride channels
• Pyrantel: Paralyzes helminth muscle Depolarization and
spastic paralysis
• Niclosamide: Inhibits production of energy Uncouples
anaerobic oxidative phosphorylation in tapeworm
mitochondria, causing decreased ATP synthesis.
• Mebendazole: Inhibits protein function Binds to tubulin
and inhibits polymerization.
• Diethylcarbamazine: Enhances phagocytosis and killing
Sensitizes microfilaria, entraps them in reticuloendothelial
system.
• Praziquantel Paralyzes helminth muscle Increases
membrane permeability, unmasks surface proteins
• Thiabendazole: Inhibits energy production, protein function
Inhibits fumarate reductase, ATP synthesis; binds to tubulin.
• Bithionol: Inhibits energy production Uncouples oxidative
phosphorylation.
• Suramin: Inhibits energy production Inhibits muscle
enzymes of glycolysis and oxygen consumption.
 Drugs for the Treatment of Nematodes
Mebendazole
• A synthetic benzimidazole compound, is effective
against a wide spectrum of nematodes.
• It is a drug of choice in the treatment of infections by
whipworm (Trichuris trichiura), pinworm (Enterobius
vermicularis), hookworms (Necator americanus and
Ancylostoma duodenale), and roundworm (Ascariasis
lumbricoides).
• Mebendazole acts by binding to and interfering
with the assembly of the parasites' microtubules
and also by decreasing glucose uptake.
• Affected parasites are expelled with the faeces.
• Mebendazole is nearly insoluble in aqueous solution.
• It undergoes first-pass metabolism to inactive compounds.

• Mebendazole is relatively free of toxic effects, although

patients may complain of abdominal pain and diarrhoea.

• It is contraindicated in pregnant women because it has

been shown to be embryotoxic and teratogenic in

experimental animals.
Pyrantel pamoate
• Is effective in the treatment of infections caused by roundworms,
pinworms, and hookworms.

• Pyrantel pamoate is poorly absorbed orally and exerts its effects in

the intestinal tract.

• It acts as a depolarizing, neuromuscular-blocking agent, causing

persistent activation of the parasite's nicotinic receptors.

• The paralyzed worm is then expelled from the host's intestinal tract.

• Adverse effects are mild and include nausea, vomiting, and diarrhoea.
Thiabendazole
• Is a synthetic benzimidazole, is effective against strongyloidiasis
caused by Strongyloides stercoralis (threadworm), cutaneous
larva migrans, and early stages of trichinosis.
• Thiabendazole, like the other benzimidazoles, affects microtubular
aggregation.
• Although nearly insoluble in water, the drug is readily absorbed on
oral administration.
• It is hydroxylated in the liver and excreted in the urine.
• The adverse effects most often encountered are
dizziness, anorexia, nausea, and vomiting.
• There have been reports of central nervous system
(CNS) symptomatology.
• Among the cases of erythema multiforme and Stevens-
Johnson syndrome reportedly caused by thiabendazole,
there have been a number of fatalities.
• Its use is contraindicated during pregnancy.
Ivermectin

• is the drug of choice for the treatment of onchocerciasis

(river blindness) caused by Onchocerca volvulus and is a
drug of first choice for cutaneous larva migrans and
Strongyloides.

• Ivermectin targets the parasite's glutamate-gated Cl - channel

receptors.

• Chloride influx is enhanced, and hyperpolarization occurs,

resulting in paralysis of the worm.
• The drug is given orally. It does not cross the blood-brain barrier
and, thus, has no pharmacologic effects in the CNS.

• However, it is contraindicated in patients with meningitis, because

their blood-brain barrier is more permeable and CNS effects might
be expected.

• Ivermectin is also contraindicated in pregnancy

• The killing of the microfilaria can result in a Mazotti-like reaction

(fever, headache, dizziness, somnolence, and hypotension).
Diethylcarbamazine

• Is used in the treatment of filariasis because of its ability to

immobilize microfilariae and render them susceptible to host
defense mechanisms.
• Combined with albendazole, diethylcarbamazine is effective
in the treatment of Wucheria bancrofti and Brugia malayi
infections.
• It is rapidly absorbed following oral administration with
meals and is excreted primarily in the urine.
• Urinary alkalosis or renal impairment may require dosage
reduction.
• Adverse effects are primarily caused by host reactions to the
killed organisms.
• The severity of symptoms is related to the parasite load and
include fever, malaise, rash, myalgias, arthralgias, and headache.
• Most patients have leukocytosis.

• Antihistamines or steroids may be given to ameliorate many of

the symptoms.
 Drugs for the Treatment of Trematodes
• The trematodes (flukes) are leaf-shaped flatworms that are
generally characterized by the tissues they infect.
• For example, they may be categorized as liver, lung, intestinal,
or blood flukes
 Praziquantel
• Trematode infections are generally treated with praziquantel.
• This drug is an agent of choice for the treatment of all forms of
schistosomiasis and other trematode infections and for cestode
infections like cysticercosis.
• Permeability of the cell membrane to calcium is increased,
causing contracture and paralysis of the parasite.
• Praziquantel is rapidly absorbed after oral administration
and distributes into the cerebrospinal fluid.
• High levels occur in the bile. The drug is extensively
metabolized oxidatively, resulting in a short half-life.
• The metabolites are inactive and are excreted through the
urine and bile.
• Common adverse effects include drowsiness, dizziness,
malaise, and anorexia, as well as gastrointestinal upsets.
• The drug is not recommended for pregnant women or
nursing mothers.
• Drug interactions due to increased metabolism have been
reported with dexamethasone, phenytoin, and
carbamazepine.
• Cimetidine, which inhibits cytochrome P450
isozymes, causes increased praziquantel levels.
• Praziquantel is contraindicated for the treatment of
ocular cysticercosis, because destruction of the
organism in the eye may damage the organ.
 Drugs for the Treatment of Cestodes

• The cestodes, or tapeworms typically have a flat,

segmented body and attach to the host's intestine.
• Like the trematodes, the tapeworms lack a mouth and a
digestive tract throughout their life cycle.
Niclosamide
• Niclosamide is the drug of choice for most cestodes
(tapeworm) infections.
• Its action has been ascribed to inhibition of the parasite's
mitochondrial phosphorylation of adenosine diphospate,
which produces usable energy in the form of adenosine
triphospate.
• Anaerobic metabolism may also be inhibited. The drug is
lethal for the cestode's scolex and segments of cestodes
but not for the ova.
• A laxative is administered prior to oral administration of
niclosamide.
 This is done to purge the bowel of all dead segments and
so preclude digestion and liberation of the ova, which
may lead to cysticercosis.

• Alcohol should be avoided within 1 day of niclosamide.

Albendazole
• Albendazole is a benzimidazole that, like the others, inhibits
microtubule synthesis and glucose uptake in nematodes.
• Its primary therapeutic application, however, is in the
treatment of cestodal infestations, such as cysticercosis
(caused by Taenia solium larvae) and hydatid disease
(caused by Echinococcus granulosis).
• Albendazole is erratically absorbed after oral
administration, but absorption is enhanced by a high-fat
meal.
• It undergoes extensive first-pass metabolism, including
formation of the sulfoxide, which is also active.
• Albendazole and its metabolites are primarily excreted
in the urine.
• When used in short-course therapy (1 to 3 days) for
nematodal infestations, adverse effects are mild and
transient and include headache and nausea.
• Treatment of hydatid disease (3 months) has a risk of
hepatotoxicity and, rarely, agranulocytosis or
pancytopenia.
• Medical treatment of neurocysticercosis is associated
with inflammatory responses to dying parasites in the
CNS, including headache, vomiting, hyperthermia,
convulsions, and mental changes.
• The drug should not be given during pregnancy or to
children under 2 years of age.
 Study Questions
Choose the ONE best answer

• A 48-year-old immigrant from Mexico presents with

seizures and other neurologic symptoms. Eggs of Taenia
solium are found upon examination of a stool specimen.
A magnetic resonance image of the brain shows many
cysts, some of which are calcified. Which one of the
following drugs would be of benefit to this individual?
A. Ivermectin.
B. Pyrantel pamoate.
C. Albendazole.
D. Diethylcarbamazine.
E. Niclosamide.
• A 56-year-old man from South America is found to
be parasitized by both schistosomes and Taenia
solium the pork tapeworm. Which of the following
anthelmintic drugs would be effective for both
infestations?
A. Albendazole.
B. Ivermectin.
C. Mebendazole.
D. Niclosamide.
E. Praziquantel.
• A 25 year old male was hospitalized with liver cyst
due to Echinococcus granulosus. He refused to
undergo surgery for removal of cyst. Therefore,
albendazole was used at high dose for 3 months.
This patient should be for the toxicity to:
(A). Gonads
(B). Kidney
(C). Liver
(D). Peripheral nerves
The drug of choice for schistosomiasis is:
(A). Albendazole
(B). Metronidazole
(C). Praziquantel

(D). Triclabendazole
• Which of the following drug causes flaccid
paralysis of ascaris?
(A). Albendazole
(B). Pyrantel pamoate
(C). Piperazine
(D). Ivermectin
THANK
YOU