A patient on clonidine for hypertension suddenly stops the drug. The mechanism of the ensuing rebound hypertension is:

• A Upregulation of peripheral alpha-1 receptors
• B Direct stimulation of beta-1 receptors
• C Inhibition of baroreceptor reflex
• D Downregulation of presynaptic alpha-2 receptors with excess noradrenaline release ✓

Explanation

Chronic clonidine use downregulates presynaptic alpha-2 receptors (autoreceptors). Upon abrupt withdrawal, the now-supersensitive pathways and reduced alpha-2-mediated inhibition allow a surge of noradrenaline release, causing rebound hypertension. This underscores why clonidine must be tapered gradually. Beta-1 receptor involvement and baroreceptor inhibition are not the primary mechanisms.

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

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