A 55-year-old farmer is brought to the emergency department after his daughter found him confused and disoriented in the tool shed at home. He has been otherwise healthy and does not take any medications. On physical examination, blood pressure is 110/70 mm Hg and pulse is 50/min. The patient's pupils are symmetric, 2 mm, and reactive to light. His eyes are tearing considerably. There are scattered wheezes bilaterally on lung auscultation. The patient's skin is clammy and he is sweating profusely. Impairment of which of the following steps at the neuromuscular junction is most likely responsible for his presentation?

Question

A 55-year-old farmer is brought to the emergency department after his daughter found him confused and disoriented in the tool shed at home.  He has been otherwise healthy and does not take any medications.  On physical examination, blood pressure is 110/70 mm Hg and pulse is 50/min.  The patient's pupils are symmetric, 2 mm, and reactive to light.  His eyes are tearing considerably.  There are scattered wheezes bilaterally on lung auscultation.  The patient's skin is clammy and he is sweating profusely.  Impairment of which of the following steps at the neuromuscular junction is most likely responsible for his presentation?

Quizplus · Accepted Answer

11ec160b_36ef_3374_9249_7397475c7197_MD0001_00 This patient's confusion, miosis and lacrimation, bradycardia, diaphoresis, and bronchospasm (bilateral wheezes) indicate a state of global muscarinic cholinergic overstimulation. This can be the result of a pharmacologic cholinomimetic (eg, carbachol, methacholine) or cholinesterase inhibitor (blocks breakdown of endogenous acetylcholine). Organophosphates are cholinesterase inhibitors that are widely used as pesticides in agriculture. They are lipid soluble; rapidly absorbed via oral, cutaneous, and inhalational routes of exposure; and readily penetrate the blood brain barrier. Organophosphates are irreversible cholinesterase inhibitors; they elicit cholinergic stimulation that lasts until new cholinesterase enzymes are synthesized. Organophosphate poisoning is treated with muscarinic antagonists (eg, atropine) and pralidoxime (PAM), a drug that reactivates acetylcholinesterase by binding organophosphates and decoupling them from the enzyme. (Choices A, B, and C) Blockade of neuronal choline uptake and inhibition of choline acetyltransferase would diminish acetylcholine synthesis. Blockade of acetylcholine uptake into axoplasmic vesicles would reduce acetylcholine release from presynaptic neurons. A decrease in acetylcholine synthesis or release would have effects opposite those observed in this patient. (Choice D) Botulinum toxin inhibits acetylcholine release from presynaptic neurons. Botulinum toxicity (botulism) causes descending skeletal muscle paralysis, typically beginning with the cranial nerves. (Choice F) Atropine is an anticholinergic agent used pharmacologically to block post-junctional acetylcholine receptors and is the antidote for organophosphate poisoning. Educational objective: Organophosphates are cholinesterase inhibitors that are widely used as pesticides in agriculture. They inhibit the breakdown of acetylcholine, leading to a state of cholinergic excess. Symptoms of organophosphate poisoning include salivation, lacrimation, diaphoresis, bradycardia, and bronchospasm. __________ References: Organophosphate and carbamate poisoning. (http://www.ncbi.nlm.nih.gov/pubmed/25455666)

A 55-Year-Old Farmer Is Brought to the Emergency Department After