A patient receiving clonidine for hypertension abruptly stops the drug. The rebound hypertensive crisis that follows is mediated primarily by:

• A Sudden increase in renin secretion due to loss of alpha-2-mediated inhibition in juxtaglomerular cells
• B Up-regulation of post-synaptic alpha-1 adrenoceptors during chronic clonidine therapy, leading to enhanced norepinephrine response
• C Reflex activation of the renin-angiotensin system secondary to vasodilation upon drug cessation
• D Loss of pre-synaptic alpha-2-mediated NE inhibition causing a surge of norepinephrine, exaggerated by up-regulated post-synaptic alpha receptors ✓

Explanation

Chronic clonidine use causes up-regulation of post-synaptic alpha adrenoceptors. On abrupt cessation, the inhibitory presynaptic alpha-2 brake is removed, resulting in a surge of NE release from nerve terminals. This NE acts on the up-regulated (sensitised) post-synaptic adrenoceptors to produce exaggerated vasoconstriction and hypertensive crisis — sometimes called 'sympathetic storm'. Renin changes and receptor up-regulation are secondary phenomena, not the primary trigger.

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

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Written and medically reviewed by the StethoPrep medical team.