Clonidine withdrawal results in rebound hypertension because of which precise receptor-level mechanism?

• A Downregulation of postsynaptic beta-1 adrenoceptors causing cardiac hypersensitivity
• B Upregulation of presynaptic alpha-2 adrenoceptors leading to excessive norepinephrine release on cessation ✓
• C Upregulation of postsynaptic alpha-1 adrenoceptors leading to increased vascular tone
• D Depletion of vesicular norepinephrine stores followed by compensatory synthesis

Explanation

Clonidine acts on presynaptic alpha-2 autoreceptors in the locus coeruleus, reducing sympathetic outflow. Chronic use leads to upregulation (supersensitivity) of these presynaptic alpha-2 receptors. When clonidine is abruptly withdrawn, the increased number of supersensitive receptors are suddenly unoccupied, leading to a massive rebound in norepinephrine release and acute sympathetic surge with severe hypertension, tachycardia, and anxiety. This is distinct from beta-receptor upregulation, which causes beta-blocker withdrawal phenomena.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.