Anthelminths and Use of Medicine

Pharmacodynamics and Pharmacokinetics

Pharmacodynamics is the study of the biochemical and physiological effects of drugs on a living organism and the mechanism of drug action. Pharmacokinetics is the study of the time-course of drug concentrations throughout a living organism, including studies of metabolites and the mathematical interpretation of the data. In short, pharmacokinetics is what the body does to the drug, as opposed to pharmacodynamics, which is what the drug does to the body.

Classification of Helminths

Helminths are classified into:

• Platyhelminths (Flatworms)

  • Cestodes (Tapeworms)

    • Albendazole

    • Niclosamide

  • Trematodes (Flukes)

    • Praziquantel

• Nematodes (Roundworms)

  • Mebendazole

  • Pyrantel pamoate

  • Ivermectin

  • Diethylcarbamazine

  • Thiabendazole

Note: Drugs stated under one class could also be used for other classes!

Drugs for treatment of nematodes

• Mebendazole

• Pyrantel pamoate

• Ivermectin

• Diethylcarbamazine

• Thiabendazole (largely replaced by other agents; use limited to topical treatment of cutaneous larva migrans)

1. Mebendazole

• Pharmacokinetics:

  • Broad-spectrum anthelmintic

  • Acts locally in the GIT; <10% of oral dose is absorbed.

• Mechanism of action:

  1. Blocks microtubule assembly in the parasite.

  2. Irreversibly inhibits glucose uptake.

2. Pyrantel pamoate

• Pharmacokinetics:

  • Poorly absorbed orally and acts locally in the GIT.

  • Effective against mature and immature forms of susceptible helminths within the intestinal tract.

  • Not effective against migratory stages in tissues or against ova.

• Mechanism of action: depolarizing, neuromuscular-blocking agent in helminths:

  • Release of acetylcholine + cholinesterase enzyme → paralysis of the worm → loss of grip to intestinal mucosa → expulsion.

3. Ivermectin

• Pharmacokinetics:

  • Used orally only, rapidly absorbed.

  • Wide tissue distribution.

  • Does not cross BBB.

• Mechanism of action:

4. Diethylcarbamazine (DEC)

• Pharmacokinetics:

  • Absorbed orally.

• Mechanism of action:

  • Exact mechanism not well established.

  • Thought to enhance susceptibility of microfilaria to the host immune system via immobilizing microfilaria and altering their surface structure.

  • Recent data: DEC acts directly on microfiliaria: DEC directly activates the Brugia TRP-2 receptor→ calcium entry → activation of SLO-1 K channels → temporary paralysis

  • Kills microfilariae

  • Active against adult worm

Drugs for treatment of trematodes

Praziquantel

• Pharmacokinetics:

  • Rapidly absorbed orally (taken with food, swallow without chewing because their bitter taste can induce vomiting).

  • Distributes to CSF.

• Mechanism of action:

  • Increases permeability of trematodes and cestodes membranes to Ca^{2+} → contraction and paralysis of parasite. The exact mechanism is not yet confirmed.

Drugs for treatment of cestodes

1. Albendazole

2. Niclosamide

1. Albendazole

• Pharmacokinetics:

  • Broad-spectrum antihelmintic

  • Absorbed orally (absorption enhanced by high-fat meals).

  • Distributes to many tissues, including CSF.

  • Extensive first-pass metabolism.

• Mechanism of action:

  • Same as mebendazole:

    1. Blocks microtubule assembly in the parasite.

    2. Irreversibly inhibits glucose uptake.

2. Niclosamide

• Pharmacokinetics:

  • Given orally.

  • Minimally absorbed from GIT (local action).

• Mechanism of action:

  • Inhibition of mitochondrial phosphorylation of ADP in the parasite.

  • Stimulation of ATPase → lethal for cestode’s scolex and segments but not ova.