A 65-year-old man comes to the emergency department due to substernal chest discomfort and intermittent palpitations that began this morning. The patient has a history of coronary artery disease and stable angina that is managed medically. He takes high-dose metoprolol, atorvastatin, and low-dose aspirin. The patient reports that he has been traveling for the past week and ran out of his medications 2 days ago. Temperature is 37 C (98.6 F), blood pressure is 148/82 mm Hg, and pulse is 112/min. ECG reveals sinus tachycardia with a 1-mm ST segment depression in the lateral leads. Which of the following is most likely responsible for this patient's presentation?

Question

A 65-year-old man comes to the emergency department due to substernal chest discomfort and intermittent palpitations that began this morning.  The patient has a history of coronary artery disease and stable angina that is managed medically.  He takes high-dose metoprolol, atorvastatin, and low-dose aspirin.  The patient reports that he has been traveling for the past week and ran out of his medications 2 days ago.  Temperature is 37 C (98.6 F), blood pressure is 148/82 mm Hg, and pulse is 112/min.  ECG reveals sinus tachycardia with a 1-mm ST segment depression in the lateral leads.  Which of the following is most likely responsible for this patient's presentation?

Quizplus · Accepted Answer

This patient with elevated blood pressure, tachycardia, palpitations, and anginal pain following recent discontinuation of metoprolol is most likely experiencing beta blocker withdrawal syndrome. With changes in environmental stimulus, the feedback mechanisms in cells adjust the density of cell surface membrane receptors to regulate sensitivity to the stimulus. Prolonged beta-adrenergic blockade, for example, stimulates an increase in surface membrane expression of beta-adrenergic receptors, a process called upregulation. When beta-adrenergic blockade is abruptly withdrawn, the increased density of beta-adrenergic receptors creates an amplified response to circulating catecholamines (ie, increased sensitivity). Because metoprolol is cardioselective and primarily blocks beta-1 receptors, abrupt cessation stimulates beta-1 receptor-mediated increased heart rate and cardiac contractility. There is also increased blood pressure due to increased cardiac output. These changes create increased oxygen demand that may cause ischemia (evidenced by ST depression on ECG) and trigger angina in patients with underlying coronary artery disease. (Choice A) Beta blocker withdrawal symptoms result from an increase in the density of beta-adrenergic receptors, leading to an amplified response to circulating catecholamines. The level of circulating catecholamines is unchanged from baseline. (Choice B) Alpha-adrenergic receptors are predominantly activated in the setting of beta blockade. On cessation of beta blocker therapy, there is redistribution of catecholamines to beta-adrenergic receptors. (Choice C) Beta-adrenergic receptors function via cyclic AMP second messaging. The increased stimulation of beta-adrenergic receptors following beta blocker cessation leads to increased cyclic AMP activity. (Choice D) Downregulation of surface membrane receptors occurs when cells are exposed to frequent agonist activity. For example, prolonged use of an alpha-1 agonist nasal spray (eg, phenylephrine) causes downregulation of alpha-1 receptors and reduced sensitivity to endogenous catecholamines. This is opposite to what is occurring in this patient. Educational objective: When exposed to a prolonged environmental stimulus, cells can adjust their sensitivity to the stimulus by upregulating or downregulating surface membrane receptors. Prolonged beta blockade leads to upregulation of beta-adrenergic receptors and increased sensitivity to circulating catecholamines, causing an enhanced beta-adrenergic response on abrupt beta blocker cessation (ie, beta blocker withdrawal syndrome). __________ References: Abrupt withdrawal of beta-blocking agents in patients with arterial hypertension. Effect on blood pressure, heart rate and plasma catecholamines and prolactin. (http://www.ncbi.nlm.nih.gov/pubmed/37093) Withdrawal of beta blocking drugs. (http://www.ncbi.nlm.nih.gov/pubmed/6125098) Pharmacology of beta-blockers: classical aspects and recent developments. (http://www.ncbi.nlm.nih.gov/pubmed/11527109)

A 65-Year-Old Man Comes to the Emergency Department Due to Substernal