Storage, Stability, CompatibilityEpinephrine HCl for injection should be stored in tight containers and protected from light. Epinephrine will darken (oxidation) upon exposure to light and air.
Do not use the injection if it is pink, brown or contains a precipitate. The stability of the injection isdependent on the form and the preservatives present, and may vary from one manufacturer toanother. Epinephrine is rapidly destroyed by alkalies, or oxidizing agents.
Epinephrine HCl is reported to be compatible with the following intravenous solutions: Dextran6% in dextrose 5%, Dextran 6% in normal saline, dextrose-Ringer's combinations, dextroselactated Ringer's combinations, dextrose-saline combinations, dextrose 2.5%, dextrose 5%(becomes unstable at a pH > 5.5), dextrose 10%, Ringer's injection, lactated Ringer's injection, normal saline, and sodium lactate 1/6 M. Epinephrine HCl is reportedly compatible with thefollowing drugs: amikacin sulfate, cimetidine HCl, dobutamine HCl, metaraminol bitartrate, andverapamil HCl.
Epinephrine HCl is reported to be incompatible with the following intravenous solutions:
Ionosol-D-CM, Ionosol-PSL (Darrow's), Ionosol-T w/ dextrose 5% (Note: other Ionosol productare compatible), sodium chloride 5%, and sodium bicarbonate 5%. Epinephrine HCl is reportedlyincompatible with the following drugs: aminophylline, cephapirin sodium, hyaluronidase, mephentermine sulfate, sodium bicarbonate, and warfarin sodium. Compatibility is dependent uponfactors such as pH, concentration, temperature, and diluents used and it is suggested to consultspecialized references for more specific information.
Pharmacology - EPINEPHRINEEpinephrine is an endogenous adrenergic agent that has both alpha and beta activity. It relaxes smooth muscle in the bronchi and the iris, antagonizes the effects of histamine, increases glycogenolysis, and raises blood sugar. If given by rapid IV injection it causes directstimulation of the heart (increased heart rate and contractility), and increases systolic blood pressure. If given slowly IV, it usually produces a modest rise in systolic pressure and a decrease in diastolic blood pressure. Total peripheral resistance is decreased because of beta effects.
Uses, IndicationsEpinephrine is employed primarily in veterinary medicine as a treatment foranaphylaxis and in cardiac resuscitation. Because of its vasocontrictive properties, epinephrine isalso added to local anesthetics to retard systemic absorption and prolong effect.
Pharmacokinetics - EPINEPHRINEEpinephrine is well absorbed following IM or SQ administration. IM injections are slightly faster absorbed than SQ administration; absorption can be expedited by massaging the injection site. Epinephrine is rapidly metabolized in the GI tract and liver after oral administration and is not effective via this route. Following SQ injection, the onset of action is generally within 5-10 minutes. The onset of action following IV administration is immediate and intensified.
Epinephrine does not cross the blood-brain barrier, but does cross the placenta and is distributedinto milk.
Epinephrine's actions are ended primarily by the uptake and metabolism of the drug into sympathetic nerve endings. Metabolism takes place in both the liver and other tissues by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) to inactive metabolites.
Contraindications/Precautions - Epinephrine is contraindicated in patients with narrow-angleglaucoma, hypersensitivity to epinephrine, shock due to non-anaphylactoid causes, during generalanesthesia with halogenated hydrocarbons or cyclopropane, during labor (may delay the secondstage) and in cardiac dilatation or coronary insufficiency. Epinephrine should also not be used incases where vasopressor drugs are contraindicated (e.g., thyrotoxicosis, diabetes, hypertension, toxemia of pregnancy). It should not be injected with local anesthetics into small appendages of thebody (e.g., toes, ears, etc.) because of the chance of necrosis and sloughing.
Use epinephrine with caution in cases of hypovolemia; it is not a substitute for adequate fluidreplacement therapy. It should be used with extreme caution in patients with a prefibrillatory cardiacrhythm, because of its excitatory effects on the heart. While epinephrine's usefulness in asystole iswell documented, it also can cause ventricular fibrillation; use cautiously in cases of ventricularfibrillation.
Adverse Effects, WarningsEpinephrine can induce a feeling of fear or anxiety, tremor, excitability, vomiting, hypertension (overdosage), arrhythmias (especially if patient has organic heart disease or has received another drug that sensitizes the heart to arrhythmias), hyperuricemia, andlactic acidosis (prolonged use or overdosage). Repeated injections can cause necrosis at the injection site.
Overdosage - Symptoms seen with overdosage or inadvertent IV administration of SQ or IM dosages can include: sharp rises in systolic, diastolic, and venous blood pressures, cardiac arrhythmias, pulmonary edema and dyspnea, vomiting, headache, and chest pain. Cerebral hemorrhages may result because of the increased blood pressures. Renal failure, metabolic acidosis and cold skin may also result.
Because epinephrine has a relatively short duration of effect, treatment is mainly supportive. If necessary, the use an alpha-adrenergic blocker (e.g., phentolamine) or a beta-adrenergic blocker (e.g., propranolol) can be considered to treat severe hypertension and cardiac arrhythmias.
Prolonged periods of hypotension may follow, which may require treatment with norepinephrine.
Drug InteractionsDo not use with other sympathomimetic amines (e.g., isoproterenol) because of additive effects and toxicity.
Certain antihistamines (diphenhydramine, chlorpheniramine, etc.) and l-thyroxine may potentiate the effects of epinephrine.
Propranolol (or other beta-blockers) may potentiate hypertension, and antagonize epinephrine's cardiac and bronchodilating effects by blocking the beta effects of epinephrine.
Nitrates, alpha-blocking agents, or diuretics may negate or diminish the pressor effects of epinephrine.
When epinephrine is used with drugs that sensitize the myocardium (halothane, high doses of digoxin) monitor for signs of arrhythmias. Hypertension may result if epinephrine is used with oxytocic agents.