Phenylephrine

Mechanism

Mechanism of Action

Potent and highly selective agonist of postsynaptic α₁ adrenergic receptors, with clinically insignificant effects on cardiac or bronchial β receptors. By selectively binding to the α₁ receptor, it activates the G_q protein cascade, increasing the cytosolic concentration of free calcium in the smooth muscle of systemic arterioles. The net result is intense peripheral arterial vasoconstriction that increases both systemic vascular resistance (SVR) and systolic and diastolic blood pressures. This pressor increase reflexively stimulates vagal tone through the carotid and aortic baroreceptors, producing a characteristic reflex bradycardia.

Pharmacokinetics

Key Pharmacokinetics

• Routes: Intravenous (bolus or continuous infusion), topical nasal, ophthalmic.
• Oral bioavailability: Low (approximately 38%) due to extensive intestinal first-pass metabolism by oxidative deamination mediated by monoamine oxidase (MAO-A).
• Metabolism: Mainly hepatic and digestive mucosa through conjugation with sulfate and oxidative metabolism.
• Half-life: 2.5 to 3 hours after conventional systemic administration.
• Excretion: Renal in the form of conjugated and free inactive metabolites (80-85%).

Indicators and dose

Approved and Off-label Indications

Approved: Treatment of hypotension induced by neuraxial anesthesia (spinal or epidural) during surgical interventions or cesarean sections; refractory distributive shock (as an alternative when seeking to avoid the arrhythmogenic β stimulus); Therapeutic ocular mydriasis and topical mucosal nasal decongestion.

Off-label: Low-flow priapism (using direct intracavernous injection to induce contraction of the corpus cavernosum).

Dosage and Adjustments

Emergency IV Bolus: 50 to 200 µ g IV every 10-15 minutes as needed to reverse acute anesthetic-induced hypotension.

Continuous Infusion: 0.5 to 2.0 µ g/kg/min or fixed dose of 40-180 µ g/min, adjusting to maintain target mean arterial pressure.

Renal/hepatic adjustment: No quantitative recommendations have been established, but caution is advised due to the possible accumulation of metabolites and prolongation of the vasoconstrictor effect.

Security

Contraindications

Absolute: Severe uncontrolled arterial hypertension, hypertrophic obstructive cardiomyopathy, previous severe sinus bradycardia.

Relative: Severe obstructive coronary artery disease, decompensated hyperthyroidism, peripheral vascular disease with intermittent claudication.

Adverse Effects (ADR)

Common: Reflex sinus bradycardia, rebound hypertension, throbbing headache, rebound nasal congestion in chronic topical use (rhinitis medication), coldness in extremities.

Serious: Cerebral hemorrhage, acute pulmonary edema due to abrupt overload of the left ventricle, refractory myocardial ischemia in predisposed patients, necrosis of the intestinal or tissue mucosa due to extravasation.

Interactions

MAO inhibitors (MAOIs): Extreme potentiation of the pressor response with risk of potentially lethal hypertensive crisis. The combination should be avoided and for 2 weeks after stopping the MAOI.

Ergot alkaloids (e.g., ergotamine): Synergy in the vasoconstrictor effect, inducing severe vascular ischemia.

Pregnancy and Breastfeeding

FDA Classification: Category C. Although it is associated with a lower incidence of fetal acidosis than ephedrine during delivery under spinal anesthesia, its chronic use should be restricted due to the risk of fetal hypoxia due to vasoconstriction of the uterine artery. There is not enough data on its excretion in breast milk.