Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning.
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.
Department of Emergency Medicine, Division of Medical Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts.
Steven B
SB
Bird
West Virginia School of Osteopathic Medicine, Lewisburg, West Virginia.
Predrag
P
Krajacic
Medical University of Sapporo, Sapporo, Japan.
Keigo
K
Sawamoto
Medical University of Sapporo, Sapporo, Japan.
Naofumi
N
Bunya
University of Pennsylvania, Perelman School of Medicine, Department of Physiology, Philadelphia, Pennsylvania.|University of Pennsylvania, Pennsylvania Muscle Institute, Philadelphia, Pennsylvania.
Emanuele
E
Loro
University of Pennsylvania, Perelman School of Medicine, Department of Physiology, Philadelphia, Pennsylvania.|University of Pennsylvania, Pennsylvania Muscle Institute, Philadelphia, Pennsylvania.
Tejvir S
TS
Khurana
D000208:Acute Disease; D000818:Animals; D004358:Drug Therapy; D008168:Lung / Q000187:drug effects / Q000473:pathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000473:pathology*; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D010575:Pesticides / Q000506:poisoning*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*
D010575:Pesticides; D020011:Protective Agents
pesticide; neuromuscular junction; poisoning