EPINEPHRINE
Clinical safety rating
safeAnimal studies have demonstrated safety
Animal studies have demonstrated safety
Emergency treatment of anaphylactic reactionsAcute asthma exacerbation (subcutaneous injection)Cardiac arrest (ACLS protocol, intravenous or intraosseous)Treatment of hypotension associated with septic shock (off-label)Treatment of severe allergic reactions (epinephrine auto-injector)Local hemostatic agent (diluted solution, off-label)
cardiac arrest
Epinephrine is a direct-acting sympathomimetic amine that stimulates alpha-1, alpha-2, beta-1, beta-2, and beta-3 adrenergic receptors. Its effects include vasoconstriction (alpha-1), bronchodilation (beta-2), increased heart rate and contractility (beta-1), and relaxation of uterine and bladder smooth muscle.
| Metabolism | Epinephrine is metabolized primarily by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver, kidneys, and other tissues. The major metabolites are metanephrine, vanillylmandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MOPEG). |
| Excretion | Primarily hepatic metabolism via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO); renal excretion of metabolites (inactive) and small fraction (<5%) unchanged. |
| Half-life | 1-2 minutes (intravenous); clinical effect termination primarily due to rapid uptake and metabolism, not elimination half-life. |
| Protein binding | Approximately 50% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.5 L/kg; reflects distribution into highly perfused tissues. |
| Bioavailability | IM: 80-100%, SC: 50-80%, oral: <2% (extensive first-pass metabolism), inhalation: 5-15%. |
| Onset of Action | IV: immediate (<1 minute), IM: 1-5 minutes, SC: 5-10 minutes, inhalation: 1-2 minutes, endotracheal: 2-3 minutes. |
| Duration of Action | IV: 5-10 minutes, IM: 1-2 hours, SC: 2-4 hours; prolonged in shock states. |
| Molecular Weight | 183.24 |
0.3-0.5 mg IM (auto-injector or syringe) every 5-15 minutes as needed for anaphylaxis; IV: 0.1-0.5 mg (1-10 mcg/min infusion) for hemodynamic support.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment; use with caution in severe renal failure due to risk of hypertension and arrhythmias. |
| Liver impairment | No specific dose adjustment recommended for Child-Pugh class A, B, or C; monitor for exaggerated effects in severe hepatic impairment. |
| Pediatric use | Anaphylaxis: 0.01 mg/kg IM (max 0.3 mg) every 5-15 minutes; IV: 0.01 mg/kg (0.1-1 mcg/min infusion) titrated to effect. |
| Geriatric use | Use lower initial doses (e.g., 0.1-0.3 mg IM) and titrate cautiously due to increased sensitivity and higher risk of adverse effects (tachyarrhythmias, hypertension, myocardial ischemia). |
| 1st trimester | Use only if clearly indicated; associated with risk of decreased uteroplacental blood flow and potential fetal hypoxia. |
| 2nd trimester | Use only if clearly indicated; may cause maternal and fetal tachycardia, hypertension, and reduced placental perfusion. |
| 3rd trimester | Use only if clearly indicated; near term may inhibit labor and cause fetal hypoxia due to vasoconstriction. |
Clinical note
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
| Placental transfer | Crosses placenta; demonstrated in animal studies and inferred from human fetal effects (tachycardia, hypertension). |
| Breastfeeding | Minimal amounts excreted into breast milk; oral bioavailability is low, so infant exposure is negligible. Use with caution in nursing mothers, especially with high doses or prolonged therapy, as theoretical risk of cardiovascular effects in infant. |
| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | FDA Pregnancy Category C. Animal studies have shown adverse fetal effects, but no adequate human studies. Epinephrine causes reduced uterine blood flow and fetal hypoxia; risk of fetal harm if used during pregnancy, especially in the second and third trimesters. Avoid in first trimester unless necessary. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG, and signs of uterine tetany. Fetal heart rate monitoring essential in pregnancy. Assess for fetal distress and placental perfusion during administration. |
| Fertility Effects | High doses may impair fertility through reduction in sperm count and motility in males; in females, may alter menstrual cycle and ovulation due to hormonal effects. Reversible upon discontinuation. |
■ FDA Black Box Warning
Epinephrine is not a substitute for immediate medical care in anaphylaxis. Patients should seek emergency medical attention immediately after use.
| Common Effects | cardiac arrest |
| Serious Effects |
Hypersensitivity to epinephrine or any componentNarrow-angle glaucomaShock (other than anaphylactic)Coronary insufficiencyCardiac dilationCerebral arteriosclerosisDuring general anesthesia with halogenated hydrocarbons (e.g., halothane) due to risk of ventricular fibrillation
| Precautions | Use with caution in patients with cardiovascular disease (e.g., coronary artery disease, hypertension, arrhythmias), hyperthyroidism, diabetes, or pheochromocytoma., May cause severe hypertension, myocardial ischemia, pulmonary edema, and cardiac arrhythmias., Avoid extravasation; can cause local tissue necrosis due to alpha-mediated vasoconstriction., May aggravate narrow-angle glaucoma., Use with caution in elderly patients and those with cerebrovascular insufficiency. |
| Food/Dietary | No specific food interactions. Avoid alcohol as it may worsen hypotension. Caffeine and other sympathomimetics (e.g., weight loss supplements) can potentiate adverse effects. |
| Clinical Pearls | Administer epinephrine IM into the vastus lateralis for anaphylaxis; avoid gluteal and IV administration in non-arrest settings due to risk of arrhythmias. Intravenous infusion requires central line and continuous hemodynamic monitoring. Use with extreme caution in patients on non-selective beta-blockers (e.g., propranolol) due to unopposed alpha-mediated hypertension. |
| Patient Advice | Seek emergency medical help immediately after using epinephrine auto-injector; symptoms may recur. · Do not delay use if anaphylaxis is suspected; early administration is crucial. · Inject into the outer middle thigh; can be done through clothing if necessary. · Massage injection site for 10 seconds after use to enhance absorption. · Always carry two auto-injectors; a second dose may be needed if symptoms persist. · Store at room temperature; protect from light and do not refrigerate. · Check expiration date regularly and replace as needed. · Train family and caregivers on proper usage. |
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