MEDizzy - A patient with a history of hypertension, heart failure, and

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Pharmacology of the cardiovascular system 2

A patient with a history of hypertension, heart failure, and peripheral vascular disease has been on oral therapy with drugs suitable for each for about three months. He runs out of medication and plans to have the prescriptions refilled in a week or so. Within a day or two after stopping his medications, he experiences an episode of severe tachycardia accompanied by tachyarrhythmias and an abrupt rise of blood pressure to 240/140 mm Hg—well above pretreatment levels. He complains of chest pain, anxiety, and a pounding headache. Soon thereafter, he suffers a hemorrhagic stroke. Which of the following drugs or drug groups the man suddenly stops taking most likely causes these responses?

ExplanationAbrupt discontinuation of clonidine has been associated with a rapidly developing and severe “rebound” phenomenon that includes excessive cardiac stimulation and a spike of blood pressure that may be sufficiently great as to cause stroke or other similar complications. Recall that clonidine is a “centrally acting α2-adrenergic agonist.” Through its central effects it reduces sympathetic nervous system tone. This, in turn, appears to cause supersensitivity of peripheral adrenergic receptors to direct-acting adrenergic agonists, including endogenous norepinephrine and epinephrine. Once, and soon after, the drug is stopped, endogenous catecholamines trigger hyper-responsiveness of all structures under sympathetic control. When ACE inhibitors (or angiotensin receptor blockers), furosemide, or nifedipine (long-acting or otherwise) are abruptly stopped, blood pressure (and blood volume, depending on the drug) will begin to rise from treatment levels, but there will be no sudden “spike” of pressure nor an “overshoot” of it. Digoxin discontinuation is not associated with the symptoms noted in the question. Besides, the half-life of digoxin (about 36 to 40 h if renal function is normal) is such that stopping the drug abruptly would not in all likelihood, lead to any significant “withdrawal” events occurring within a day or two of discontinuation. There is no reason to predict that suddenly stopping warfarin would cause tachyarrhythmias, hypertension, or hemorrhagic stroke—and certainly not within 24 to 48 h.