A patient with pheochromocytoma crisis is given phentolamine intravenously. Within minutes, the blood pressure drops sharply but is accompanied by tachycardia. Which receptor mechanism best explains the tachycardia seen after phentolamine administration?

• A Direct agonist action at cardiac beta-1 adrenoceptors
• B Reflex baroreceptor-mediated vagal withdrawal only
• C Blockade of cardiac muscarinic M2 receptors
• D Blockade of presynaptic alpha-2 receptors allowing increased norepinephrine release and beta-1 stimulation ✓

Explanation

Phentolamine is a non-selective alpha blocker that blocks both alpha-1 and alpha-2 receptors. Blockade of presynaptic alpha-2 autoreceptors removes the inhibitory feedback on norepinephrine release, markedly increasing NE at the synapse; this excess NE then stimulates cardiac beta-1 receptors producing tachycardia. Reflex tachycardia due to hypotension also contributes, but the presynaptic alpha-2 mechanism is the pharmacologically specific explanation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.