Anti-helminthic Drugs

Presentation by Group 4 Pharmacology.

 GROUP 4 MEMBERS

1. KIVUMBI HAMDAN 20/U/O493/LSM

2. NAMUSOKE RUTH 20/U/0258/LSM/PS
3. AGUTI GRACE 20/U/0039/LSM/PS
4. CHEBET VIASCO 20/U/0608/LSM
5. NAKAZIBA BABIRYE HOPE 20/U/0250/LSM/PS
6. AKELLO LUCY 19/U/0154/LSM/PS
7. AKELLO KETTY 19/U/0152/LSM/PS
8. ATIM CISSY ODNGO 19/U/0227/LSM/PS
9. AYURU EDITH 20/U/0143/LSM/PS
10.ERONG JOSHUA 20/U/0182/LSM/PS
11.OBOT BRIAN 20/U/0271/LSM/PS
12.NABAKOOZA ELIZABETH 20/U/0238/LSM/PS
13. OCEPA AMOS 19/U/0344/LSM/PS
14.ANGOM BRENDA 19/U/0208/LSM/PS
15.KYOMIGISHA JOSELYN 20/U/0212/LSM
16.OJOK JONATHAN 20/U/0325/LSM/PS
17.NAKALEMA JOSEPHINE VANESA 20/U/0246/PHL
18.ATAI JANET MARY 20/U/0114/PHL
19.ACAR AMBROSE 20/U/0479/PHL/PS
20.GENA KETTY 20/U/0463/PHL/PS
21.OGWAL WALTER OLINGA 18/U/0240/PHL/PS
22.AKUGIZIBWE LUCKY 20/U/0589/PHL
23.NAKWANG IRENE FORTUNATE 19/U/0322/PHL/PS
 INTRODUCTION
• Major groups of helminths (worms) that infect humans:
Nematodes- roundworms
Trematodes- flukes
Cestodes- true tapeworms
Anthelmintic drugs are aimed at metabolic targets that present in the parasite but
absent/ have different characteristics than those of the host.
Aims of anthelmintic drug therapy:
i. Elimination of the organisms from the host
ii. ii. Controlling spread of infections.
 Drugs for treatment of nematodes

Nematodes are elongated roundworms with a complete digestive

system.
They cause infections in following:
• Intestine
• Blood
• Other tissues
 MEBENDAZOLE

Mebendazole, a synthetic benzimidazole compound

It is a first-line drug for treatment of infections caused by:
Whipworms (Trichuris trichiura), Pinworms (Enterobius
vermicularis), Hookworms (Necator americanus/Ancylostoma
duodenale), Roundworms (Ascaris lumbricoides).
 Mebendazole (cont.)

Mode of action
• Mebendazole inhibits assembly of microtubules in the parasite.
• It also irreversibly blocks glucose uptake.
• Affected parasites are expelled in the feces.
Adverse effects
 Abdominal pain
 Diarrhea.
 Mebendazole(Cont.…)

Contraindications
• Mebendazole should not be used in pregnant women.
• However, in mass prevention or treatment programs,
mebendazole or albendazole may be used in the second/
third trimester.
 Pyrantel pamoate
Pyrantel pamoate is also effective in treatment of following infections:
I. Roundworms
II. Pinworms
III. Hook-worms .
Mode of action
It depolarizes/blocks neuromuscular-junction, causing release of acetylcholine and
inhibition of cholinesterase. This leads to paralysis of the worm. The paralyzed
worm releases its hold on the intestinal tract and is expelled
Pyrantel pamoate is poorly absorbed orally and exerts its effects in the
intestinal tract.
Adverse effects: Nausea, Vomiting, Diarrhea
 Thiabendazole

• Thiabendazole a synthetic benzimidazole.

• It is potent/ has broad-spectrum.
• Current use is topical treatment of cutaneous larva migrants
(creeping eruption).
• It is highly toxic and has been replaced by other safer drugs.
 Ivermectin
• Ivermectin is the drug of choice for treatment for :
• Cutaneous larva migrants
• Strongyloidiasis
• Onchocerciasis (river blindness) caused by onchocerca volvulus
• It kills microfilariae O.volvulus but has no activity against adult
worms.
• Ivermectin is also useful in the treatment of pediculosis (lice)
and scabies.
 Ivermectin(Cont.…)
Mode of action
• Ivermectin targets the glutamate-gated chloride channel receptors.  Chloride
influx is enhanced, and hyperpolarization occurs. This results in paralysis and
death of the worm.
• Adverse effects
• The killing of microfilaria in onchocerciasis can result in a dangerous Mazzotti
reaction: Fever, headache, dizziness, somnolence, and hypotension.
• The severity of this reaction is related to parasite load. This can be treated with
antihistamines or steroids
 PK: The drug is given orally and does not readily cross the blood–brain barrier.
The severity of this reaction is related to parasite load. This can be treated with
antihistamines or steroids.
 Contraindication: Ivermectin should not be used in pregnancy
 Diethylcarbamazine
Diethylcarbamazine is the drug of choice for filariasis caused by
infection with Wuchereria bancrofti and Brugia malayi.
It kills microfilariae and also has activity against adult worms.
It is used in combination of antifilarial drugs
(diethylcarbamazine/albendazole or ivermectin /albendazole for
prophylaxis of filariasis in countries where filariasis is endemic.
Diethylcarbamazine is rapidly absorbed following oral administration
with meals and is excreted mainly in the urine.
 Diethylcarbamazine(Cont.…)

Adverse effects
Fever, nausea, vomiting, arthralgia/headache. Contraindication

Diethylcarbamazine should be avoided in patients with severe Mazzotti

reactions with onchocerciasis because it can accelerate blindness
 Drugs for treatment of trematodes

Trematodes (flukes) are leaf-shaped flatworms generally characterized by the

tissues they infect e.g.:
• Liver
• Lung
• Intestinal
• Blood
 Praziquantel
Praziquantel is a drug of choice for treatment of the following:
• All forms of schistosomiasis
• Other trematode infections
• Cestode infections e.g. Taeniasis.
Praziquantel is also used off-label in treatment of cysticercosis caused by
taenia solium larvae.
Mode of action
• Increases permeability of the cell membrane to calcium. This causes
contracture and paralysis of the parasite.
 Praziquantel(Cont.…)

Pk
• Praziquantel should be taken with food and not chewed due to its
bitter taste.  It is rapidly absorbed after oral administration and
distributes into the cerebrospinal fluid (CSF).
• The drug is extensively metabolized, and inactive metabolites are
excreted mainly in urine.
Adverse effects: Dizziness , malaise , headache ,GI upset.
 Praziquantel(Cont.…)
Drug interactions
Dexamethasone, phenytoin, rifampin, and carbamazepine
may increase the metabolism of praziquantel.
Cimetidine causes increased praziquantel levels.
Contraindications
Praziquantel is contraindicated for treatment of ocular
cysticercosis, because destruction of the organism in the eye
may cause irreversible damage.
 Drugs for the treatment of cestodes

• The cestodes, or “true 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 an alternative to praziquantel for treatment of taeniasis,
diphyllobothriasis, and other cestode infections.
Mode of action
It inhibits the mitochondrial phosphorylation of adenosine diphosphate (ADP) in
the parasite, making it lethal for the cestode’s scolex and segments but not for the
ova. Anaerobic metabolism may also be inhibited. A laxative is administered prior
to oral administration to purge the bowel of all dead segments and to enhance
digestion and liberation of the ova.
Caution: Alcohol should be avoided within 1 day of niclosamide use
 Albendazole
Albendazole, also a benzimidazole effective against most known
nematodes.
Mode of action
It inhibits microtubule synthesis and glucose uptake in nematodes.
Its primary therapeutic application, however, is in treatment of cestodal
infestations e.g. cysticercosis and hydatid disease-caused by larval stage
of Echinococcus granulosus.
Albendazole is also very effective in treating microsporidiosis, a fungal
infection.
 Albendazole(Cont.…)
Pk
Albendazole is erratically absorbed after oral administration,
but absorption is enhanced by a high-fat meal.
The drug distributes widely, including the CSF.
It undergoes extensive first-pass metabolism, and forms an
active sulfoxide.
 Albendazole(Cont.…)

Adverse effects
When used in short-course therapy (1-3 days) for nematodal infestations, adverse
effects are mild and transient and include headache and nausea.
Treatment of hydatid disease (3mths) 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, fever, and
seizures
 The End

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