80. Anthelminthic drugs

Page created on October 27, 2019. Last updated on January 7, 2022 at 22:52

Helminths

Helminths are parasitic worms. They’re categorized like this:

• Helminths (worms)
  • Plathelminths (flatworms)
    • Cestodes (tapeworms)
    • Trematodes (flukes)
  • Nemathelminths (roundworms)
    • Nematodes (threadworms)
      • Intestinal nematodes
      • Filariae

Antihelminthic drugs

Classified according to mechanism of action:

• Drugs against flatworms
  • Drugs which bind tubulin
    • Benzimidazoles
  • Drugs which interfere with energy production
    • Niclosamide
  • Drugs which act on Ca²⁺ receptors
    • Praziquantel
• Drugs against roundworms
  • Drugs which bind tubulin
    • Benzimidazoles
  • Neuromuscular blocking drugs
    • Pyrantel
    • Oxantel
    • Levamisole
  • Drugs acting on GABA receptors
    • Piperazine
  • Drugs acting on GABA receptors and glutamate-gated chloride channels
    • Ivermectin
  • Drugs which interfere with energy production
    • Pyrvinium
  • Other
    • Diethylcarbamazine

Benzimidazoles

Benzimidazoles, also called bendazoles, are antihelminthic drugs derived from benzimidazole.

Drugs:

• Mebendazole
• Albendazole

Indications:

These are broad-spectrum antihelminthics. Albendazole is more efficacious than mebendazole.

Some sensitive worms:

• Enterobius
• Ascaris
• Ancylostoma
• Trichuris
• Intestinal trichinella

Mechanism of action:

Benzimidazoles inhibit the polymerization of β-tubulin, thus interfering with microtubule-dependent functions like glucose uptake, motility and DNA replication.

Mechanisms of resistance:

• Mutation in β-tubulin, decreasing the affinity to benzimidazoles
• Lower expression of β-tubulin

Pharmacokinetics:

Benzimidazoles are very lipophilic. Their oral absorption is poor but increases substantially with concurrent intake of fat-rich food. They have strong plasma protein binding.

Adverse effects:

• Both
  • GI symptoms
  • Neutropaenia
• Albendazole
  • Mild hepatotoxicity

Piperazine

Indications:

• Nematodes
  • Ascaris (roundworm)
  • Enterobius (threadworm)

Mechanism of action:

Piperazine is a GABA receptor agonist. It opens GABA-gated chloride channels in nematodes, which causes flaccid paralysis of the worms. They are then excreted by normal peristaltic movements.

Adverse effects:

• Neurotoxicity (seizures)

It’s contraindicated in epileptics.

Levamisole

Indications:

• Ascaris (roundworm)

Also used to cut cocaine, because its crystals are similar to those of cocaine.

Mechanism of action:

Levamisole is a nicotinic receptor agonist, causing overstimulation of the neuromuscular junction and resulting paralysis, just like depolarizing muscle relaxants.

Adverse effects:

• CNS toxicity
• Agranulocytosis

Pyrantel and oxantel

(Not among the most important antihelminthics to know, according to the seminar teacher).

Indications:

Intestinal parasites, parasites in the GI lumen.

Mechanism of action:

These drugs are nicotinic receptor agonists and cholinesterase inhibitors, thereby acting as depolarizing muscle relaxants.

Pharmacokinetics:

These drugs are not orally absorbed and are therefore only effective against parasites in the GI lumen.

Niclosamide

Indications:

Intestinal forms of tapeworms.

Mechanism of action:

Niclosamide inhibits glucose uptake, oxidative phosphorylation and the citric acid cycle.

Pharmacokinetics:

Niclosamide is not orally absorbed and is therefore only effective against tapeworms in the GI lumen.

Praziquantel

Praziquantel is a quinoline derivate.

Indications:

• Schistosomiasis
• Cysticercosis

Mechanism of action:

Praziquantel increases the permeability of Ca²⁺ across the parasite’s membranes. This causes tonic paralysis.

Pharmacokinetics:

Praziquantel is well absorbed but has significant first-pass effect in the liver, so very little reaches the systemic circulation.

Adverse effects:

• Rare
• GI symptoms

Contraindications:

Worm infections of the eye.

Unlike what the seminar says praziquantel is safe in pregnancy, a property which is important for its role in national disease control programs.

Pyrvinium

(Not among the most important antihelminthics to know, according to the seminar teacher).

Indications:

Enterobius.

Mechanism of action:

Pyrvinium inhibits glucose absorption.

Pharmacokinetics:

Pyrvinium is not absorbed in the GI tract.

Diethylcarbamazine

Indications:

• Loiasis
• Lymphatic filariasis

It is no longer used to treat patients with onchocerciasis (river blindness) because it can cause the Mazzotti reaction.

Mechanism of action:

Poorly understood. Parasites exposed to diethylcarbamazine in vitro seem unbothered. It is thought that the drug changes the parasite so that it becomes more susceptible to phagocytosis. It also inhibits arachidonic acid metabolism in the host.

Adverse effects:

Using diethylcarbamazine to treat onchocerciasis can cause the Mazzotti reaction, a potentially life-threatening reaction with pruritus, adenopathy, etc. This reaction can be treated with steroids.

Ivermectin

(Not among the most important antihelminthics to know, according to the seminar teacher).

Indications:

• Filariae
  • Especially onchocerciasis (river blindness)
• Cutaneous larva migrans
• Strongyloides
• Scabies

Mechanism of action:

Ivermectin opens glutamate-gated Cl^– channels, which causes pharyngeal paralysis. It also activates GABA receptors, causing tonic paralysis.

Adverse effects:

Ivermectin can cause a Mazzotti reaction, especially when used to treat onchocerciasis.