A 45-year-old woman on clonidine for hypertension abruptly stops the medication. She develops severe hypertension, tachycardia, and diaphoresis 18 hours later. The mechanism responsible is:

• A Rebound decrease in central noradrenergic outflow
• B Compensatory downregulation of baroreceptor reflex sensitivity
• C Direct withdrawal activation of beta-1 receptors in the heart
• D Upregulation and supersensitivity of peripheral alpha-2 receptors leading to norepinephrine surge ✓

Explanation

Clonidine withdrawal syndrome results from upregulation of central and peripheral alpha-2 adrenoceptors during chronic therapy. When the drug is stopped, the supersensitive receptors mediate a massive sympathetic outburst with norepinephrine surge, causing rebound hypertension, tachycardia, and sweating. Treatment involves restarting clonidine or using phentolamine with a beta-blocker.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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