A patient receiving clonidine for hypertension abruptly stops the drug and presents 24 hours later with severe hypertension, palpitations, and diaphoresis. The mechanism of rebound hypertension is primarily:

• A Upregulation of postsynaptic α1 adrenoceptors during treatment
• B Increased renin secretion after removal of β2-mediated inhibition at juxtaglomerular cells
• C Abrupt loss of central α2-mediated inhibition of sympathetic outflow, causing norepinephrine surge ✓
• D Rebound increase in peripheral β1 receptor sensitivity

Explanation

Clonidine acts on central α2 receptors in the nucleus tractus solitarius and rostral ventrolateral medulla to suppress sympathetic outflow. Chronic use leads to upregulation of presynaptic β2 receptors at sympathetic nerve terminals. On abrupt withdrawal, central α2 inhibition is lost and enhanced norepinephrine release from upregulated terminals produces sympathetic hyperactivity. This is managed by reinstituting clonidine or using labetalol (not pure β-blockers, which would worsen hypertension by unopposed α activation).

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

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