A 25-year-old man is brought to the emergency department after being found unresponsive. He has a history of schizoaffective disorder and previous suicide attempts by prescription medication overdose. The patient was recently started on haloperidol and sertraline. Temperature is 40.6 C (105 F), blood pressure is 180/98 mm Hg, and pulse is 112/min. On examination, the patient is obtunded and diffusely rigid without clonus. Laboratory studies show serum creatinine of 3.2 mg/dL, creatine kinase of 75,000 U/L, and leukocytes of 16,000/mm³. The antidote for this patient's current condition most likely has which of the following mechanisms of action?

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11ec160b_3c13_45e2_9249_f569eee5e43f_MD0001_00 This patient has neuroleptic malignant syndrome (NMS) likely caused by an overdose of haloperidol. NMS is a life-threatening adverse reaction most commonly resulting from the use of antipsychotics (neuroleptic) medications, which block dopamine receptors in the brain. NMS presents clinically with diffuse muscle rigidity, high fever, autonomic instability (hypertension, tachycardia), and altered sensorium. Laboratory findings include creatine kinase elevation due to rhabdomyolysis, which can result in acute renal failure. The mainstay of treatment is to discontinue the causative agent and provide supportive care (eg, intravenous hydration). In severe cases, dantrolene can be administered, which antagonizes ryanodine receptors and inhibits calcium release from the sarcoplasmic reticulum. Bromocriptine, a dopamine agonist, has also shown clinical benefit in NMS. (Choice A) Activation of presynaptic voltage-gated calcium channels at the neuromuscular junction will trigger calcium influx into the terminal bulb. This will increase the release of acetylcholine from the terminal bulb onto the muscle endplate and, therefore, promote skeletal muscle contraction. (Choice B) Serotonin receptor antagonists (eg, cyproheptadine) can be used to treat serotonin syndrome. Similar to NMS, serotonin syndrome can present with altered mental status and autonomic instability (diaphoresis, hypertension, hyperthermia, tachycardia). However, serotonin syndrome commonly presents with hyperreflexia and myoclonus (not diffuse rigidity) and gastrointestinal symptoms (nausea, diarrhea, vomiting). (Choice C) Blockade of central dopamine D2 receptors in the brain leads to the extrapyramidal symptoms (eg, diffuse rigidity) observed in NMS. (Choice D) Inhibition of acetylcholinesterase results in increased acetylcholine at the neuromuscular junction, promoting skeletal muscle activation and contraction. Procholinergic agents should be avoided in NMS as they may exacerbate symptoms. Educational objective: Neuroleptic malignant syndrome is a life-threatening reaction to antipsychotic medications characterized by diffuse muscle rigidity, hyperthermia, autonomic instability, and altered sensorium. The antipsychotic should be stopped and supportive care provided; dantrolene, a ryanodine receptor blocker that inhibits calcium release from the sarcoplasmic reticulum, is an effective antidote. __________ References: Neuroleptic malignant syndrome: a neuro-psychiatric emergency: recognition, prevention, and management. (http://www.ncbi.nlm.nih.gov/pubmed/29061403) Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management. (http://www.ncbi.nlm.nih.gov/pubmed/22563571)

A 25-Year-Old Man Is Brought to the Emergency Department After