Anthelmintics (anti-worms), Slides of Pharmacology

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Anthelmintics

Contents

⚫ Helminthiasis

⚫ Anthelmintics

⚫ Benzimidazoles

⚫ Albendazole

⚫ Pyrantel

⚫ Piperazine

Classification of Helminths

❑ Helminths are generally classified into 2 major groups. These are-

1. Nematodes (also known as round worms)
2. Flatworms a) Trematodes (also known as flukes) b) Cestodes (also known as tapeworms)

Nematodes Trematodes (Flukes)

Cestodes (Tape worms)

Ascaris lumbricoides Enterobius Vermicularis

Taenia Solium Ancylostoma duodenale

Schistoma mansoni (^) Wucheria bancrofti

Loa loa

Anthelmintics

Anthelmintics are drugs that can either kill (vermicide) or expel (vermifuge) the infesting parasites.

May act by causing : ❑ Paralysis of the worm. ❑ Damaging the worm leading to partial digestion or rejection by immune mechanisms. ❑ Interfere with the metabolism of the worm.

Vermicide drugs mostly include the benzimidazoles, for e.g. Albendazole, Mebendazole, Thiabendazole etc. Vermifuge drugs include piperazine, pyrantel and ivermectin etc.

Benzimidazoles

Albendazole

Mechanism of Action:

2. Albendazole leads to impaired uptake of glucose and depletes their glycogen stores.

Albendazole

Mechanism of Action:

3. Albendazole also prevents the formation of spindle fibers needed for cell division, which in turn blocks egg production and development; existing eggs are prevented from hatching.

Albendazole

Pharmacokinetics:

• Oral absorption of albendazole varies among species, with 1–5% of the drug being successfully absorbed in humans. The absorption also largely depends on gastric pH. Oral absorption is especially increased with a fatty meal, as albendazole dissolves better in lipids, allowing it to cross the lipid barrier created by the mucus surface of the GI tract. To target intestinal parasites, albendazole is taken on an empty stomach in order to stay within the gut.
• In humans, albendazole metabolites are mostly excreted in the bile, with only a small amount being excreted in the urine (less than 1%) and feces. Dose: 200 mg/day, 400 mg/day, 800 mg/day etc. Maximum dose: 800 mg/day

Side Effects:

• The most common side effects by albendazole are, experienced by over 10% of people, headache and abnormal liver function.
• An estimated 1–10% of people experience abdominal pain, nausea or vomiting, dizziness or vertigo, temporary hair loss and fever. Contraindications: Albendazole is a pregnancy class D drug in Australia and pregnancy class C in the United States. It is contraindicated in the first trimester of pregnancy, and should be avoided up to one month before conception. While studies in pregnant rats and rabbits have shown albendazole to be teratogenic, albendazole has been found to be safe in humans during the second and third trimesters.

Albendazole

Piperazine

❑ Piperazine was first introduced as an anthelmintic in 1953. ❑ Their mode of action is generally by paralyzing parasites , which allows the host body to easily remove or expel the invading organism. The neuromuscular effects are thought to be caused by working as GABA agonist to increase Cl- entry in cells of the worms. ❑ This inhibits neuromuscular transmission in worms ultimately leading to paralysis and death. ❑ Side effects include GI disturbance, neurotoxicity , allergic reactions. ❑ Contraindicated in Epilepsy, Impaired liver or kidney functions and pregnancy.

Levamisole and Ivermectin

❑ Levamisole works as a nicotine receptor agonist. ❑ It overstimulates the helminths cellular activity and eventually causes paralysis of the worms.

❖ Ivermectin kills by interfering with nervous system and muscle function of worms. ❖ The drug binds to glutamate-gated chloride channels (GluCls) in the membranes of the worm’s nerve and muscle cells, causing increased permeability to chloride ions, resulting in cellular hyper-polarization, followed by paralysis and death.