EPINEPHRINE
Clinical safety rating: safe
Animal studies have demonstrated safety
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
| Breastfeeding | Epinephrine is excreted into breast milk in small amounts. M/P ratio unknown. Oral bioavailability is low, so systemic effects in infant are unlikely. Use with caution, monitor infant for signs of sympathetic stimulation. |
| 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. |
■ 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 component of the formulation.","Narrow-angle glaucoma (relative contraindication in emergency situations).","Use during second stage of labor may delay delivery.","Concurrent use with non-selective beta-blockers (e.g., propranolol) may cause severe hypertensive crisis.","Use in patients with hypovolemic shock (except as temporary measure in cardiac arrest)."]
| 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."] |
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| 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. |
| 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. |