A 4-year-old boy is brought to the hospital after several episodes of vomiting. The boy's mother reports that he was playing at a local park prior to the onset of illness. While cleaning him after the first episode of emesis, she found several small brown mushrooms clenched in his hands and brought samples with her. The boy is otherwise healthy and takes no medications. He is intubated due to somnolence and admitted to the intensive care unit. Analysis of the mushroom samples determines that the main poison stimulates muscarinic receptors. Which of the following is the most direct effect of this poison?

Question

A 4-year-old boy is brought to the hospital after several episodes of vomiting.  The boy's mother reports that he was playing at a local park prior to the onset of illness.  While cleaning him after the first episode of emesis, she found several small brown mushrooms clenched in his hands and brought samples with her.  The boy is otherwise healthy and takes no medications.  He is intubated due to somnolence and admitted to the intensive care unit.  Analysis of the mushroom samples determines that the main poison stimulates muscarinic receptors.  Which of the following is the most direct effect of this poison?

Quizplus · Accepted Answer

11ec160b_3cd6_bc90_9249_d369fe687f7b_MD0001_00 Muscarine, a toxin found in certain mushrooms, acts as a muscarinic (M) agonist in place of acetylcholine, resulting in an increase in parasympathetic nervous system activity. The M₂ and M₃ subtype receptors are responsible for most of the toxicities seen in patients. Although the walls of peripheral blood vessels lack cholinergic innervation, M₃ receptors are present on the endothelial surface. Activation of M₃ receptors promotes synthesis of nitric oxide (NO), an endothelium-derived relaxing factor. NO diffuses into vascular smooth muscle cells, activating guanylate cyclase and increasing intracellular cyclic-GMP. Increased levels of cyclic-GMP activate myosin light chain phosphatase, which dephosphorylates myosin and prevents interaction of the myosin head with actin, resulting in smooth muscle relaxation and vasodilation. Vasodilation results in hypotension, with persistently low blood pressure leading to somnolence due to inadequate cerebral perfusion. In contrast, activation of M₃ receptors in other sites leads to a G-protein-coupled increase in intracellular calcium, resulting in smooth muscle contraction. Clinically, this contraction manifests as detrusor bladder muscle contraction (Choice A), pupillary constriction or miosis (Choice E), and exocrine gland secretion (eg, salivation) (Choice F). (Choice B) M₂ receptors are predominantly found in cardiac muscle. Activation of M₂ receptors leads to a G-protein-coupled decrease in intracellular cyclic-AMP and opens potassium channels to slow depolarization. This combination results in decreased inotropy (less contractility) and chronotropy (decreased heart rate). (Choice C) Juxtaglomerular cells in the kidney release renin in response to decreased renal perfusion pressure. A muscarinic agonist would not have a direct effect on renin release, although the peripheral vasodilation and bradycardia might indirectly lead to renin release. Educational objective: Activation of muscarinic receptors by acetylcholine or cholinergic agonists results in peripheral vasodilation due to synthesis of nitric oxide in endothelial cells, which leads to vascular smooth muscle relaxation (eg, hypotension). Muscarinic receptor activation in other sites causes smooth muscle contraction. __________ References: Muscarinic toxicity among family members after consumption of mushrooms. (http://www.ncbi.nlm.nih.gov/pubmed/23833447) New pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors. (http://www.ncbi.nlm.nih.gov/pubmed/23597304)

A 4-Year-Old Boy Is Brought to the Hospital After Several