Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning

Ann N Y Acad Sci. 2016 Jun;1374(1):86-93. doi: 10.1111/nyas.13111. Epub 2016 Jun 3.

Abstract

Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ). Thus, the NMJ is potentially a target-rich area for the development of new therapies for acute OP poisoning. In this manuscript, we discuss what is known about the IMS and studies investigating the use of nicotinic ACh receptor antagonists to prevent or mitigate NMJ dysfunction after acute OP poisoning.

Keywords: pesticide; neuromuscular junction; poisoning.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Drug Therapy*
  • Lung / drug effects
  • Lung / pathology
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / pathology*
  • Organophosphate Poisoning / drug therapy*
  • Pesticides / poisoning*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*

Substances

  • Pesticides
  • Protective Agents