Epinephrine - Drug Monograph

Introduction

Epinephrine (also known as adrenaline) is a naturally occurring catecholamine that serves as both a hormone and neurotransmitter. As a medication, it represents one of the most critical agents in emergency medicine, with life-saving applications in anaphylaxis, cardiac arrest, and severe bronchospasm. First isolated in 1901 by Jokichi Takamine, epinephrine remains an essential component of emergency kits worldwide.

Mechanism of Action

Epinephrine exerts its effects through stimulation of α- and β-adrenergic receptors. The α₁-adrenergic stimulation causes vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema. β₁-adrenergic activation increases heart rate, myocardial contractility, and cardiac output. β₂-adrenergic stimulation results in bronchodilation, decreased inflammatory mediator release, and increased glycogenolysis. The combination of these effects makes epinephrine particularly effective in reversing the pathophysiological processes of anaphylaxis and cardiac arrest.

Indications

• First-line treatment for anaphylaxis and anaphylactic shock
• Cardiac arrest (including ventricular fibrillation, pulseless ventricular tachycardia, asystole, and pulseless electrical activity)
• Severe asthma exacerbations unresponsive to standard therapy
• Local anesthesia adjunct (to prolong duration of action and reduce systemic absorption)
• Hypotension/shock states (continuous infusion)
• Croup (nebulized)
• Open-angle glaucoma (topical ophthalmic solution)

Dosage and Administration

• Adults: 0.3-0.5 mg IM in anterolateral thigh every 5-15 minutes as needed
• Children: 0.01 mg/kg IM (maximum 0.3 mg) every 5-15 minutes as needed

• IV: 1 mg every 3-5 minutes during resuscitation
• Alternative: High-dose epinephrine (0.1-0.2 mg/kg) may be considered

• Initial: 1-10 mcg/min IV, titrated to effect
• Preparation: Typically 1 mg in 250 mL NS (4 mcg/mL)

• Elderly: Use with caution due to increased cardiovascular risk
• Renal/hepatic impairment: No dosage adjustment required
• Pregnancy: Category C; use if clearly indicated

Pharmacokinetics

Contraindications

• Hypersensitivity to epinephrine or any component
• Narrow-angle glaucoma
• Use with caution in patients with known cardiovascular disease
• Relative contraindication in patients receiving non-selective beta-blockers (risk of severe hypertension)

Warnings and Precautions

• May cause potentially fatal arrhythmias in patients with underlying heart disease
• Use with extreme caution in patients with hypertension, hyperthyroidism, diabetes, or elderly patients
• Tissue necrosis may occur with extravasation of IV administration
• Auto-injector devices require proper training for effective use
• Not recommended for routine use in hemorrhagic or traumatic shock

Drug Interactions

• Beta-blockers: May antagonize cardiac effects and precipitate severe hypertension
• MAO inhibitors, TCAs, levothyroxine: Potentiate cardiovascular effects
• Digoxin: Increased risk of arrhythmias
• Ergot alkaloids: Enhanced vasoconstrictive effects
• Inhalation anesthetics: Increased risk of ventricular arrhythmias

Adverse Effects

• Anxiety, tremors, headache
• Tachycardia, palpitations
• Pallor, dizziness
• Nausea, vomiting

• Ventricular arrhythmias
• Myocardial ischemia or infarction
• Pulmonary edema
• Severe hypertension
• Cerebral hemorrhage
• Tissue necrosis with extravasation

Monitoring Parameters

• Continuous cardiac monitoring during IV administration
• Blood pressure and heart rate frequently
• Respiratory status and oxygenation
• Electrolytes and glucose in prolonged therapy
• Injection site for signs of extravasation
• Mental status and urine output

Patient Education

• Carry auto-injector at all times if prescribed for anaphylaxis
• Understand how and when to use auto-injector (practice with trainer device)
• Seek immediate medical attention after use for anaphylaxis
• Recognize signs of anaphylaxis: difficulty breathing, swelling, hives
• Inform all healthcare providers of epinephrine use
• Store at room temperature, protect from light
• Check expiration date regularly and replace as needed
• Report chest pain, irregular heartbeat, or severe headache after use

References

1. Simons FE, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37. 2. Link MS, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18 Suppl 2):S444-S464. 3. Epinephrine injection prescribing information. USP DI, 2023. 4. Lieberman P, et al. Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. 5. Brown SG. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol. 2005;5(4):359-364. 6. Trzeciak S, et al. Epinephrine dosing in anaphylaxis: how much is enough? Ann Emerg Med. 2006;47(4):373-375.