1. Anti-helminthic Drugs
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture 14
April 06, 2013

3. Helminthes
Due to human travel and migration, worms (helminthes) can spread to geographic locations that previously had been free of a particular organism
Three groups of worms: roundworms (nematodes), flukes (trematodes), and tapeworms (cestodes)
Anthelminthics are drugs that act either locally to expel worms from the GIT or systemically to eradicate adult helminthes or developmental forms that invade organs or tissues
As with antibiotics, the anthelmintic drugs are aimed at metabolic targets that are present in the parasite
The geographic distribution of helminthiasis is cosmopolitan. Eradicate: destroy

4. Anti-helminthic Drugs
Three major groups of drugs available
Drugs for nematodes
Drugs for trematodes
Drugs for cestodes

5. Drugs for Nematodes Benzimidazoles Pyrantel pamoate Ivermectin
Mebendazole
Thiabendazole
Albendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazine

6. Mebendazole Effective against a wide spectrum of nematodes
It is a drug of choice in the treatment of infections with whipworm (Trichuris trichuria), pinworm (enterobiasis vermicularis), hookworm (Necator americanus), and roundworm (Asariasis lumbricoides)

7. Mebendazole: Mechanism of Action
Benzimidazoles produce many biochemical changes in susceptible nematodes e.g. inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation
Acts by binding to and interfering with the synthesis of the parasite’s microtubules and also by decreasing glucose uptake

8. Mebendazole: Pharmacokinetics
It is nearly insoluble in aqueous solution, and little of an oral dose is absorbed by the body unless taken with a high fat meal
It is contraindicated in pregnancy, because it has been shown to be embryotoxic and teratogenic in experimental animals
Affected parasites are expelled with the feces

9. Pyrantal Pamoate
Pyrantel pamoate, along with mebendazole, is effective in the treatment of infections caused by roundworms, pinworms, and hookworms
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 diarrhea

10. Ivermectin Drug of choice for the treatment of onchocerciasis
Targets the parasite's glutamate-gated Cl- channel receptors. Chloride influx is enhanced, and hyper polarization 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
Also contraindicated in pregnancy

11. Drugs for Trematodes
Trematode infections are treated with praziquantel
Permeability of cell membrane to calcium is increased, causing contracture and paralysis of the parasite
Rapidly absorbed after oral administration and distributes into the CSF. High levels occur in the bile
The drug is extensively metabolized oxidatively
The metabolites are inactive and are excreted through the urine and bile
Adverse effects include drowsiness, dizziness, and anorexia, as well as GI upsets
Not recommended for pregnant women or nursing mothers
Contracture: shortening of muscle

12. Drugs for Cestodes
Niclosamide is the drug of choice for most cestode (tapeworm) infections
MAO: Inhibition of the parasite's mitochondrial phosphorylation of ADP, which produces usable energy in the form of ATP
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 the drug. 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
phosphorylation of ADP, which produces usable energy in the form of ATP
Cysticercosis is an infection by a parasite called Taenia solium (T. solium), a pork tapeworm

13. Myalgias: Muscle pain; Arthralgias: Joint pain

14. Diethylcarbamazine Used in the treatment of filariasis
Rapidly absorbed following oral administration with meals and is excreted primarily in the urine
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, rash, myalgias, arthralgias, and headache
Myalgias: Muscle pain; Arthralgias: Joint pain