Clonidine withdrawal syndrome produces a hypertensive crisis because:

• A Upregulation of postsynaptic alpha-1 receptors during therapy leads to supersensitivity
• B Clonidine blocks renal dopamine receptors and withdrawal unmasks renin-angiotensin activation
• C Tolerance develops to the vasodilatory effect but not to the bradycardic effect
• D Rebound increase in central and peripheral sympathetic activity as the alpha-2 agonist effect is removed, with supersensitized alpha-1 receptors ✓

Explanation

Chronic clonidine therapy suppresses central sympathetic outflow via alpha-2A receptors in the locus coeruleus and nucleus tractus solitarius. Prolonged agonist exposure causes compensatory upregulation of postsynaptic alpha-1 and alpha-2 adrenergic receptors. Abrupt withdrawal removes the central inhibition, leading to a rebound surge of norepinephrine acting on supersensitized peripheral receptors, producing acute hypertensive crisis with tachycardia, sweating, and anxiety. Management is reinstitution of clonidine or labetalol.

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

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