A 68-year-old woman comes to the office due to recurrent syncopal episodes. The most recent incident occurred 3 days ago while she was walking to her car and lasted about 1 minute. She was able to resume her normal activities afterward although she felt tired. She had no preceding chest pain or palpitations. The patient has had 2 similar syncopal episodes in the past 2 months, along with frequent episodes of intermittent dizziness. Medical history includes hypertension and chronic kidney disease. She takes lisinopril, amlodipine, and clonidine daily. Blood pressure is 155/85 mm Hg and pulse is 44/min. Heart and lung sounds are normal. After the offending medication is discontinued, she has no further syncopal episodes. The drug responsible for this patient's episodes most likely functions through which of the following mechanisms?

Question

A 68-year-old woman comes to the office due to recurrent syncopal episodes.  The most recent incident occurred 3 days ago while she was walking to her car and lasted about 1 minute.  She was able to resume her normal activities afterward although she felt tired.  She had no preceding chest pain or palpitations.  The patient has had 2 similar syncopal episodes in the past 2 months, along with frequent episodes of intermittent dizziness.  Medical history includes hypertension and chronic kidney disease.  She takes lisinopril, amlodipine, and clonidine daily.  Blood pressure is 155/85 mm Hg and pulse is 44/min.  Heart and lung sounds are normal.  After the offending medication is discontinued, she has no further syncopal episodes.  The drug responsible for this patient's episodes most likely functions through which of the following mechanisms?

Quizplus · Accepted Answer

11ec160b_3ba1_717d_9249_092947e4809c_MD0001_00 This patient's syncopal episodes are due to bradycardia and decreased peripheral vascular resistance caused by clonidine. Clonidine is used in the treatment of severe or refractory hypertension. It exerts its effects on both heart rate and blood pressure by stimulating presynaptic alpha-2 adrenergic receptors in the rostral ventrolateral medulla (area responsible for basal and reflex control of sympathetic activity). This effect results in a subsequent decrease in presynaptic release of norepinephrine and decreased sympathetic outflow causing both bradycardia and a decrease in peripheral vascular resistance. Normally, to maintain cerebral perfusion while standing, a baroreceptor-mediated increase in sympathetic drive causes vasoconstriction to increase peripheral resistance and increased heart rate and contractility to aid cardiac output. These changes facilitate a corrective increase in blood pressure to prevent a drop in cerebral perfusion. However, when an orthostatic stress is applied (eg, upright posture) to this patient with attenuated sympathetic outflow due to clonidine, she is unable to maintain cerebral perfusion and syncope results. Lisinopril and amlodipine can also contribute to orthostatic syncope by impairing peripheral vasoconstriction, but their effects are not as profound as those of clonidine because they do not affect heart rate; in fact, they may result in reflex tachycardia. (Choice A) Decreased presynaptic release of acetylcholine occurs with certain toxins (eg, botulinum) and some medications (eg, aminoglycoside antibiotics). This effect leads to muscle weakness and does not contribute to syncope. (Choice C) Beta blockers (eg, atenolol) block beta-1 adrenoreceptors in the sinoatrial node, which can lead to bradycardia and contribute to orthostatic syncope. Clonidine does not block adrenoreceptors; it reduces central sympathetic output. (Choice D) Nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil) block calcium channels in the atrioventricular node and ventricular myocardium, resulting in slowed cardiac conduction (ie, heart rate) and decreased contractility, which can contribute to orthostatic syncope. Amlodipine, a dihydropyridine calcium channel blocker, has minimal effect on the heart and functions primarily as a direct vasodilator. (Choice E) Class III antiarrhythmics (eg, dofetilide) bind to and block the potassium channels responsible for phase 3 repolarization of the cardiac action potential. This effect does not contribute to orthostatic syncope, but it can prolong the QT interval and increase the risk of polymorphic ventricular tachycardia (ie, torsade de pointes), a serious cause of cardiac syncope. Educational objective: Clonidine, an antihypertensive agent, stimulates central alpha-2 adrenergic receptors, causing a decrease in presynaptic release of norepinephrine and a decrease in sympathetic outflow. This prevents the normal baroceptor-mediated increase in peripheral vascular resistance and heart rate during standing and can cause orthostatic syncope. __________ References: A case report of clonidine induced syncope: a review of central actions of an old cardiovascular drug. (http://www.ncbi.nlm.nih.gov/pubmed/29433586)

A 68-Year-Old Woman Comes to the Office Due to Recurrent