A 45-year-old woman on clonidine for hypertension abruptly stops the drug. Which receptor-level mechanism explains the rebound hypertension?

• A Up-regulation of peripheral beta1-adrenergic receptors
• B Up-regulation of postsynaptic alpha2-adrenergic receptors and supersensitivity to catecholamines ✓
• C Inhibition of pre-synaptic alpha2 autoreceptors leading to massive norepinephrine release
• D Sensitization of imidazoline I1 receptors in the brainstem

Explanation

Chronic clonidine therapy suppresses sympathetic outflow via central alpha2 agonism; during this period, postsynaptic alpha2 and alpha1 receptors are up-regulated (supersentitivity). Abrupt withdrawal allows a surge of catecholamines to act on these up-regulated receptors, causing rebound hypertension often more severe than baseline. Option C describes the pharmacological effect of clonidine itself, not withdrawal. Options A and D are not the primary withdrawal mechanisms.

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

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