Generic Name

Epinephrine

Mechanism

Epinephrine is a *non‑selective adrenergic agonist* that stimulates α‑ and β‑adrenergic receptors via the G‑protein–mediated cascade.
• α‑1 adrenoceptor activation → vascular smooth‑muscle contraction → ↑ systemic vascular resistance & ↑ blood pressure.
• β‑1 adrenoceptor activation → ↑ myocardial contractility and heart rate.
• β‑2 adrenoceptor activation → bronchodilation and vasodilation in skeletal muscle vasculature; facilitates mucous gland cooling.
• α‑2 adrenoceptor inhibition → reduced presynaptic norepinephrine release (modest stimulatory effect).

The net result is rapid cardiovascular support, improved airway patency, and reversal of anaphylactic hypotension.

Pharmacokinetics

• Absorption
• *Intramuscular (IM)*: slow, sustained release; bioavailability ~80 %.
• *Intravenous (IV)*: 100 % bioavailability; peak effect within seconds.
• *Nasal*: ~80 % absorption in 5–10 min, useful for mild anaphylaxis.
• Distribution: widely distributed due to high lipophilicity; crosses the blood‑brain barrier in low amounts.
• Metabolism: ester hydrolysis by plasma butyryl‑ and N‑acetyl‑transferases → inactive metabolites (e.g., 4‑hydroxy‑epinephrine).
• Elimination: renal excretion; half‑life ~3–5 min IV, 23–28 min IM.
• Drug‑Drug Interactions:
• β‑blockers → reduced β‑adrenergic effects, risk of unopposed α‑1 vasoconstriction.
• MAO inhibitors, sympathomimetics → additive cardiovascular effects.

Indications

• Anaphylaxis – emergency intramuscular/IV therapy.
• Severe acute bronchospasm (status asthmaticus) – IV epinephrine or nebulized β‑agonist synergy.
• Cardiac arrest – first‑line in early resuscitation (Phase I vasopressor).
• Laryngospasm – IM or IV dose.
• Localized anaphylaxis – topical or intra‑dermal for skin and mucosal reactions.
• Topical anesthesia adjunct – 1 % dilution for mucosal vessels.

Contraindications

• Severe hypertension or uncontrolled angina may worsen; cautious titration needed.
• Known hypersensitivity to epinephrine or its excipients.
• Catecholamine excess disorders (e.g., pheochromocytoma, carcinoid, MS, neuroblastoma) – avoid routine use.
• Beta‑blocker therapy – monitor for unopposed α1‑mediated vasoconstriction and potential hypotension.
• Pregnancy & lactation – category B; use only when clearly indicated.

Warnings
• Short duration; consider repeat dosing or infusion for sustained effect.
• Monitor for arrhythmias, myocardial ischemia, and cerebrovascular events.

Dosing

Preparation tip – Use a 1 : 10 000 solution for anaphylaxis; a 1 : 1 000 solution for cardiac arrest; avoid dilution errors.

Adverse Effects

• Common
• Palpitations, tachycardia, arrhythmias (PR prolongation).
• Hypertension & headaches.
• Anxiety, tremor, sweating.
• Local site pain, erythema, bruising (IM).
• Serious
• Myocardial ischemia / infarction (especially in patients with coronary artery disease).
• Severe arrhythmias: ventricular fibrillation, Torsades de Pointes.
• Cerebral vasoconstriction → transient ischemia or stroke.
• Hyperglycemia due to glycogenolysis.
• Severe bronchospasm (rare with β‑agonist synergy).

Monitoring

• Vital signs: BP, HR, RR, SpO₂ continuously.
• Cardiac rhythm: 12‑lead ECG during infusion.
• Metabolic panel: serum glucose, electrolytes, lactate (if prolonged use).
• Pulmonary function: peak expiratory flow/ FEV₁ (if severe asthma).
• Temperature and mental status: watch for hyperthermia, agitation.

Clinical Pearls

• “Rule of 6” – In anaphylaxis, keep a stock of 6 mg (0.6 mL of 1:10 000) ready; 3 mg is the maximum in most guidelines.
• IM Insertion – Use the mid‑anterior thigh for adults and the anterolateral thigh for children; avoid the gluteal area to reduce intramuscular uptake variability.
• “First‑dose, second‑dose” – If symptoms persist after the first 0.3 mg dose, give a repeat 0.3 mg immediately; do not wait >10 min.
• Avoid “double‑dose” – Many clinicians double‑dose due to fear of under‑treatment; this increases risk of arrhythmias. Keep to recommended intervals.
• Epinephrine Auto‑Injectors – The cartomized auto‑injector (1:10 000) is usually 0.3/0.5 mg; re‑check the expiration and the device before use.
• For cardiac arrest, the recommended 1 mg dose corresponds to a 1:10 000 concentration; aspirate an extra 0.5 mL from the syringe to counteract dead space.
• In pediatric patients, weight‑based dosing (0.01 mg/kg) ensures the safety margin while maintaining efficacy.
• IV Infusion – When continuous infusion is required (e.g., in shock), titrate to MAP ≥65 mm Hg or MAP + 30 mm Hg from baseline.
• Cross‑reactivity – A patient allergic to epinephrine may still tolerate a first‑line dose for life‑threatening anaphylaxis; consider epinephrine before skin testing.

Key takeaway – Epinephrine’s pharmacologic potency requires precise dosing, vigilant monitoring, and clear understanding of its rapid onset and short half‑life. Master these fundamentals, and the drug remains a cornerstone of acute emergency care.