|Trade names||Regitine, Oraverse|
|Drug class||Alpha blocker|
|Main uses||High blood pressure in pheochromocytoma, following norepinephrine entry into soft tissues, hypertensive emergencies|
|Side effects||Abdominal pain, nausea, diarrhea, flushing, stuffy nose, low blood pressure with standing|
|intravenous (IV) or intramuscular (IM)|
|Onset of action||IV < 2min; IM < 20 min|
|Duration of action||IV up to 30 min; IM up to 4 hrs|
|Typical dose||5 mg|
|Elimination half-life||19 minutes|
|Chemical and physical data|
|Molar mass||281.359 g·mol−1|
|3D model (JSmol)|
Phentolamine, sold under the brand name Regitine among others, is a medication used to treat high blood pressure in pheochromocytoma, following norepinephrine entry into soft tissues, and hypertensive emergencies. It is given by injection. When injected into a vein effects occur within 2 minutes and last up to 30 minutes.
Common side effects include abdominal pain, nausea, diarrhea, flushing, stuffy nose, and low blood pressure with standing. Other side effects may include myocardial infarction and priapism. Safety in pregnancy is unclear. It is a alpha blocker.
Phentolamine was approved for medical use in the United States in 1952. In the United States it costs about 460 USD per dose as of 2021. In the United Kingdom it is available together with aviptadil for the treatment of erectile dysfunction.
It also has usefulness in the treatment of cocaine-induced cardiovascular complications, where one would generally avoid β-blockers (e.g. metoprolol), as they can cause unopposed α-adrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. It is important to note that phentolamine is not a first-line agent for this indication. Phentolamine should only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, and calcium channel blockers.
When given by injection it causes blood vessels to dilate, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection.
It may be stored in crash carts to counteract severe peripheral vasoconstriction secondary to extravasation of peripherally placed vasopressor infusions, typically of norepinephrine. Epinephrine infusions are less vasoconstrictive than norepinephrine as they primarily stimulate β receptor more than α receptors, but the effect remains dose-dependent.
Phentolamine is marketed in the dental field as a local anesthetic reversal agent. Branded as OraVerse, it is a phentolamine mesylate injection designed to reverse the local vasoconstrictor properties used in many local anesthetics to prolong anesthesia.
Non-selective α-blockers can cause a much more pronounced reflex tachycardia than the selective α1 blockers. Like the selective α1 blockers, phentolamine causes a relaxation of systemic vasculature, leading to hypotension. This hypotension is sensed by the baroreceptor reflex, which results in increased sympathetic nerve firing on the heart, releasing norepinephrine. In response, the β1 adrenergic receptors on the heart increase their rate, contractility, and dromotropy, which help to offset the decrease in systemic blood pressure. Unlike the α1 selective blockers, phentolamine also inhibits the α2 receptors, which function predominantly as presynaptic negative feedback for norepinephrine release. By abolishing this negative feedback phentolamine leads to even less regulated norepinephrine release, which results in a more drastic increase in heart rate.
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