Adrenaline (Epinephrine)

Mechanism

Mechanism of Action

Endogenous agonist with high affinity for all adrenergic receptors (α₁, α₂, β₁, β₂, β₃). At low plasma concentrations, the β₂ effect (vasodilation in skeletal muscle and bronchodilation) predominates. At high doses, the vasoactive α₁ effect is imposed (systemic vasoconstriction). Its activation of cardiac β₁ receptors produces an increase in heart rate (chronotropism), contraction force (inotropism) and AV node conduction velocity (dromotropism), mediated by the adenylate cyclase cascade and the consequent phosphorylation of L-type calcium channels.

Pharmacokinetics

Key Pharmacokinetics

• Routs: Intramuscular (IM) in the anterolateral aspect of the thigh (faster and more constant absorption in anaphylaxis), intravenous (IV, reserved for emergencies and monitored), endotracheal, subcutaneous (inconsistent), nebulized.
• Oral bioavailability: Virtually zero due to rapid enzymatic inactivation in the gastrointestinal tract and first-pass metabolism.
• Metabolism: Mainly intracellular and hepatic by the enzymes Catechol-O-methyltransferase (COMT) and Monoamine oxidase (MAO), converting into vanillylmandelic acid (VVM) and metanephrines.
• Elimination half-life: Approximately 2 to 3 minutes after intravenous administration.
• Excretion: Renal in the form of metabolites conjugated with sulfate and glucuronide.

Indicators and dose

Approved and Off-label Indications

Approved: Cardiorespiratory arrest (VF/pulseless VT, asystole, PEA), severe anaphylaxis, refractory cardiogenic and distributive shock, control of superficial local hemostasis, infantile laryngotracheal croup (nebulized).

Off-label: Symptomatic bradycardia refractory to atropine in perioperative critical care.

Dosage and Adjustments

Cardiorespiratory Arrest: 1 mg IV/IO of 1:10,000 solution (0.1 mg/mL) every 3-5 minutes.

Anaphylaxis: 0.3 to 0.5 mg IM of 1:1,000 solution (1 mg/mL) into the anterolateral thigh. Repeat in 5-15 minutes if necessary.

Pediatrics (Anaphylaxis): 0.01 mg/kg IM of 1:1,000 solution (maximum 0.3 mg per dose).

Renal/hepatic adjustment: No formal dose adjustment is required, but strict monitoring is advised due to the increased risk of systemic cardiovascular toxicity.

Security

Contraindications

Absolute: There are no absolute contraindications in the context of anaphylaxis or cardiopulmonary resuscitation.

Relative: Severe ischemic heart disease, ventricular tachyarrhythmias, narrow-angle glaucoma, pheochromocytoma, active labor (can inhibit uterine contractions due to the β₂ effect).

Adverse Effects (ADR)

Common: Anxiety, headache, distal muscle tremor, palpitations, diaphoresis, skin pallor due to local vasoconstriction.

Serious: Hypertensive crisis with cerebral hemorrhage, acute lung edema (due to massive increase in ventricular afterload), potentially lethal ventricular arrhythmias (ventricular fibrillation), myocardial ischemia/acute myocardial infarction, local tissue necrosis in case of IV extravasation.

Interactions

Non-selective β-blockers: They can cause a severe hypertensive reaction and reflex bradycardia because α₁ stimulation is not compensated by β₂-mediated vasodilation (unopposed vasoconstriction).

Tricyclic antidepressants and MAOIs: Pronounced potentiation of the pressor effect due to blocking neuronal reuptake or enzymatic degradation.

Halogenated anesthetics (e.g., halothane): Sensitization of the myocardium to the development of catecholamine-induced arrhythmias.

Pregnancy and Breastfeeding

FDA Classification: Category C. It crosses the placenta and can induce fetal anoxia by vasoconstriction of the uteroplacental vessels. It is secreted in breast milk, but its low oral bioavailability minimizes the risk to the infant.

Extravasation of vasoactive catecholamines

The infusion of adrenaline through peripheral venous lines carries the risk of extravasation and local ischemic tissue necrosis. If extravasation is observed, the area should be immediately infiltrated with Phentolamine (rapid α adrenergic antagonist) in doses of 5 to 10 mg diluted in 10 mL of physiological saline solution to reverse extreme vasoconstriction.