A 28-year-old man is found unresponsive by his roommate. The roommate states the patient returned late last night after a party, and this morning he was unable to wake the patient up. Paramedics find the patient without respirations and pulse and declare him dead. Autopsy examination shows hemorrhage in the basal ganglia and midbrain that extends into the third ventricle. There is no arteriosclerosis or fibrinoid necrosis of the arterioles. Scattered areas of infarcted subendocardial myocardium are also seen. A substance with which of the following synaptic effects most likely predisposed this patient to death?

Question

A 28-year-old man is found unresponsive by his roommate.  The roommate states the patient returned late last night after a party, and this morning he was unable to wake the patient up.  Paramedics find the patient without respirations and pulse and declare him dead.  Autopsy examination shows hemorrhage in the basal ganglia and midbrain that extends into the third ventricle.  There is no arteriosclerosis or fibrinoid necrosis of the arterioles.  Scattered areas of infarcted subendocardial myocardium are also seen.  A substance with which of the following synaptic effects most likely predisposed this patient to death?

Quizplus · Accepted Answer

11ec160b_3b04_4700_9249_b7efed3388c0_MD0001_00 This young man who experienced sudden, unexpected death and has autopsy evidence of a large hemorrhagic stroke and scattered myocardial infarction most likely experienced cocaine toxicity. The cardiovascular effects of cocaine toxicity result from impaired reuptake of catecholamine neurotransmitters, including norepinephrine and dopamine, due to inhibition of the presynaptic monoamine transporter. Cocaine toxicity can cause stroke via the following mechanisms: Stimulation of cerebral artery vasospasm primarily via increased levels of intrasynaptic dopamine. Blood pressure is increased via both vasoconstriction and increased sympathetic tone (ie, increased contractility and heart rate), encouraging dissection of large cerebral arteries and rupture of small cerebral vessels. This allows lacunar infarcts to occur in young patients (in the absence of the arteriosclerosis and fibrinoid necrosis that develop with prolonged hypertension and facilitate these infarcts in older patients). Increased activation of platelets and stimulation of prothrombotic mediators (eg, thromboxane) encourage thrombus formation. In the heart, similar effects combined with an increase in myocardial oxygen demand (due to increased contractility, afterload, and heart rate) contribute to the propensity for myocardial ischemia and infarction. (Choice A) Beta blockers bind to postsynaptic adrenergic receptors and can prevent some of the cardiac effects of cocaine toxicity (the cardiac adrenergic response is primarily controlled by beta-1 receptors). However, beta blockers may worsen the alpha receptor-mediated vasoconstriction of cocaine toxicity (due to unopposed alpha stimulation) and are typically avoided. (Choice B) Cathecol-O-methyltransferase (COMT) metabolizes catecholamines after they are released into the synapse. COMT inhibitors (eg, entacapone) are sometimes used to treat Parkinson disease (by slowing the breakdown of intrasynaptic dopamine). (Choice D) Reserpine decreases (rather than increases) formation of presynaptic catecholamine vesicles by irreversibly blocking vesicular monoamine transporter-2. This medication is sometimes used to treat hypertension or agitated psychosis. Methamphetamine, a common recreational drug with similar effects to cocaine, displaces catecholamines from synaptic vesicles into the cytosol, causing them to diffuse (rather than exocytose) into the synapse. (Choice E) Metyrosine, a tyrosine analogue and competitive inhibitor of tyrosine hydroxylase, decreases (rather than increases) the presynaptic synthesis of catecholamines. It is sometimes used to treat pheochromocytoma. Educational objective: Cocaine blocks the presynaptic reuptake of catecholamine neurotransmitters, including norepinephrine and dopamine. With cocaine toxicity, excessive postsynaptic stimulation by catecholamines can lead to arterial vasospasm and increased sympathetic drive, resulting in increased risk of stroke and myocardial infarction.

A 28-Year-Old Man Is Found Unresponsive by His Roommate