GIT- system modulePharmacology 9

Anthelmintic drugsFaculty of Medicine

The Hashemite University

Arwa Al Anber( MD, PhD)

Helminths

Three major groups of helminths(worms) that infect humans:

• Nematodes

• Trematodes

• Cestodes

Anthelmintic drugs

• Aimed at metabolic targets that are present in the parasite but

either are absent from or have different characteristics than those

of the host.

• Eliminating the organisms from the host.

• Controlling spread of infections.

Nematodes• Nematodes are elongated roundworms that possess a complete digestive

system.

• They cause infections of the intestine as well as the blood and tissues.

• Includes:

1. Whipworms (Trichuris trichiura)

2. Pinworms (Enterobius vermicularis)

3. Hookworms (Necator americanus and Ancylostoma duodenale)

4. Roundworms (Ascaris lumbricoides)

5. Wuchereria bancrofti, Brugia malayi, and Brugia timori.

6. Onchocerciasis

7. Strongyloidiasis

8. Trichinella spiralis

Drugs for the treatment of Nematodes

1- Mebendazole :

• A first-line agent for the treatment of infections caused by:

whipworms (Trichuris trichiura), pinworms (Enterobius vermicularis),

hookworms (Necator americanus and Ancylostoma duodenale), and

roundworms (Ascaris lumbricoides)

• Act by binding to parasite β-tubulin and inhibiting microtubule polymerization in the parasite.

• Adverse effects:

1. Abdominal pain

2. Diarrhea.

Drugs for the treatment of Nematodes

2- Pyrantel pamoate:

• Is effective in the treatment of infections caused by roundworms, pinworms, and hookworms.

• Pyrantel pamoate is poorly absorbed after oral administration and is only effective against intestinal infections.

• It acts as a depolarizing, neuromuscular-blocking agent, causing release of acetylcholine and inhibition of cholinesterase, leading to paralysis of the worm.

• CHEMOTHERAPY OF HELMINTIC

• INFECTIONS: FOR NEMATODES

Drugs for the treatment of Nematodes

3- Ivermectin:

• Ivermectin is the drug of choice for the treatment of:

• Strongyloidiasis, and onchocerciasis (river blindness, although not curative due to lack of activity in adult worms).

• Ivermectin targets the glutamate-gated chloride channel receptors. Chloride influx is enhanced, and hyperpolarization occurs, resulting in paralysis and death of the worm.

• The killing of the microfilaria in onchocerciasis can result in a dangerous Mazzottireaction (fever, headache, dizziness, somnolence, and hypotension).

• The severity of this reaction is related to parasite load. Antihistamines or steroids may be given to ameliorate the symptoms.

Drugs for the treatment of Nematodes

4- Diethylcarbamazine:

• Is the drug of choice for filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori.

• It kills the microfilariae and has activity against adult worms.

• In countries where filariasis is endemic, a combination of antifilarial drugs (either diethylcarbamazine and albendazole or ivermectin and albendazole) may be used annually as preventive chemotherapy.

• Adverse effects : fever, nausea, vomiting, arthralgia, and headache.

Characteristics of and therapy for commonly encountered nematode

infections.

Trematodes

• The trematodes (flukes) are leaf-shaped flatworms that are generally

characterized by the tissues they infect (for example, liver, lung, intestinal, or

blood.

• Include:

1. Schistosoma mansoni, Schistosoma japonicum, Schistosoma haematobium.

2. Clonorchis sinensis

3. Paragonimus westermani

Drugs for the treatment of Trematodes

Praziquantel:

• An agent of choice for the treatment of all forms of schistosomiasis, other

trematode infections, and cestode infections such as taeniasis.

• Praziquantel causes contracture and paralysis of parasites by increasing the

permeability of the cell membrane to calcium.

• Adverse effects: dizziness, malaise, and headache and gastrointestinal upset.

• Praziquantel is contraindicated for the treatment of ocular cysticercosis,

because destruction of the organism in the eye may cause irreversible damage.

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.

• Include:

1. Echinococcus granulosus

2. Taenia solium

3. Taenia saginata

4. Diphyllobothrium latum

Drugs for the treatment of Cestodes

1- Niclosamide:

• Is an alternative to praziquantel for the treatment of taeniasis, diphyllobothriasis, and other cestode infections.

• 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.

• 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.

Drugs for the treatment of Cestodes

2- Albendazole:• Inhibits microtubule synthesis and glucose uptake.

• Is used to treat cestodal infestations, such as cysticercosis and hydatid disease (caused by larval stage of Echinococcus granulosus).

• Also, effective against most nematodes.

• 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 central nervous system (CNS), including headache, vomiting, fever, and seizures.