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Acute human toxicity of macrocyclic lactones
1Department of Environmental and Occupational Medicine, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.. ccyang@vghtpe.gov.tw
Current Pharmaceutical Biotechnology
|November 2, 2011
Summary
Macrocyclic lactones like ivermectin are effective parasiticides and insecticides. While generally safe, large ingestions can cause severe toxicity by affecting nerve and muscle cells, requiring supportive care.
Area of Science:
- Pharmacology and Toxicology
- Parasitology
- Entomology
Background:
- Macrocyclic lactones, including avermectins and milbemycins, are fermentation-derived compounds used as parasiticides and insecticides.
- These compounds target invertebrate nerve and muscle cells by activating glutamate-gated chloride channels or affecting gamma-aminobutyric acid (GABA) receptors, leading to paralysis and death.
Purpose of the Study:
- To review the mechanisms of action, therapeutic uses, and toxic effects of macrocyclic lactones.
- To discuss the safety profile and management of adverse events associated with ivermectin and related compounds.
Main Methods:
- Literature review of studies on macrocyclic lactones, including avermectins and milbemycins.
- Analysis of pharmacologic and toxicologic mechanisms.
- Review of clinical data on efficacy, tolerability, and adverse effects.
Main Results:
- Ivermectin, the first macrocyclic lactone, is effective and well-tolerated for treating parasite infestations in animals and humans.
- Other macrocyclic lactones are used for crop protection and animal health.
- Adverse effects of ivermectin are typically mild and transient; severe effects are rare but can occur with large ingestions, potentially crossing the blood-brain barrier (BBB) and causing GABA-mimetic toxicity.
Conclusions:
- Macrocyclic lactones share common mechanisms of action involving invertebrate nerve and muscle cells.
- Ivermectin and related compounds offer significant benefits in treating parasitic infections and controlling pests.
- While generally safe, awareness of potential toxicity from large non-therapeutic exposures is crucial, with prognosis dependent on managing severe hypotension and respiratory failure.
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