indication

Used to treat anaphylaxis and sepsis. Also one of the body's main adrenergic neurotransmitters.

pharmacology

Epinephrine is indicated for intravenous injection in treatment of acute hypersensitivity, treatment of acute asthmatic attacks to relieve bronchospasm, and treatment and prophylaxis of cardiac arrest and attacks of transitory atrioventricular heart block with syncopal seizures (Stokes-Adams Syndrome). The actions of epinephrine resemble the effects of stimulation of adrenergic nerves. To a variable degree it acts on both alpha and beta receptor sites of sympathetic effector cells. Its most prominent actions are on the beta receptors of the heart, vascular and other smooth muscle. When given by rapid intravenous injection, it produces a rapid rise in blood pressure, mainly systolic, by (1) direct stimulation of cardiac muscle which increases the strength of ventricular contraction, (2) increasing the heart rate and (3) constriction of the arterioles in the skin, mucosa and splanchnic areas of the circulation. When given by slow intravenous injection, epinephrine usually produces only a moderate rise in systolic and a fall in diastolic pressure. Although some increase in pulse pressure occurs, there is usually no great elevation in mean blood pressure. Accordingly, the compensatory reflex mechanisms that come into play with a pronounced increase in blood pressure do not antagonize the direct cardiac actions of epinephrine as much as with catecholamines that have a predominant action on alpha receptors.

mechanism of action

Epinephrine works via the stimulation of alpha and beta-1 adrenergic receptors, and a moderate activity at beta-2 adrenergic receptors.

toxicity

Skin, LD₅₀ = 62 mg/kg (rat)

biotransformation

Epinephrine is rapidly inactivated in the body and is degraded by enzymes in the liver and other tissues. The larger portion of injected doses is excreted in the urine as inactivated compounds and the remainder either partly unchanged or conjugated. The drug becomes fixed in the tissues and is inactivated chiefly by enzymatic transformation to metanephrine or normetanephrine either of which is subsequently conjugated and excreted in the urine in the form of sulfates and glucuronides. Either sequence results in the formation of 3-methoxy-4-hydroxy-mandelic acid which also is detectable in the urine. Main metabolic enzymes include MAO and COMT

absorption

Usually this vasodilator effect of the drug on the circulation predominates so that the modest rise in systolic pressure which follows slow injection or absorption is mainly the result of direct cardiac stimulation and increase in cardiac output.

half life

2 minutes

route of elimination

Renal

drug interactions

Acebutolol: Hypertension, then bradycardia

Alseroxylon: Increased arterial pressure

Amitriptyline: The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.

Amoxapine: The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of epinephrine.

Atenolol: Hypertension, then bradycardia

Betaxolol: Beta-Blockers such as betaxolol may enhance the vasopressor effect of epinephrine. Monitor for increases in pressor effects of alpha-/beta-agonists if used in patients receiving beta-blocker therapy (including ophthalmic products). Beta1-selective (i.e., “cardioselective”) agents may confer a more limited risk if used in low enough doses to allow them to retain their selectivity. The amount of epinephrine used in dental procedures as part of local anesthetic administration is not likely to be of clinical concern. Infiltrating larger volumes of local anesthetics for other surgical procedures (e.g., more than 0.06mg epinephrine) may cause clinically-relevant problems. Patients with allergies that require carrying and periodically using subcutaneous epinephrine (e.g., bee sting kits) should probably avoid the use of beta blockers.

Bevantolol: Hypertension, then bradycardia

Bisoprolol: Hypertension, then bradycardia

Carteolol: Hypertension, then bradycardia

Carvedilol: Hypertension, then bradycardia

Clomipramine: The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine.

Deserpidine: Increased arterial pressure

Desipramine: Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Epinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Desvenlafaxine: Desvenlafaxine may increase the tachycardic and vasopressor effects of epinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.

Doxepin: The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of epinephrine.

Entacapone: Entacapone may increase the effect and toxicity of the sympathomimetic, epinephrine.

Ergonovine: Possible marked increase of arterial pressure

Esmolol: Hypertension, then bradycardia

Guanethidine: Epinephrine may decrease the effect of guanethidine.

Imipramine: The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of epinephrine.

Isocarboxazid: Increased arterial pressure

Labetalol: Hypertension, then bradycardia

Linezolid: Possible increase of arterial pressure

Methyldopa: Increased arterial pressure

Methylergonovine: Possible marked increase of arterial pressure

Metoprolol: Hypertension, then bradycardia

Midodrine: Increased arterial pressure

Moclobemide: Moclobemide increases the sympathomimetic effect of epinephrine.

Nadolol: Hypertension, then bradycardia

Nortriptyline: The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of epinephrine.

Oxprenolol: Hypertension, then bradycardia

Oxytocin: Possible marked increase of arterial pressure

Pargyline: Increased arterial pressure

Penbutolol: Hypertension, then bradycardia

Phenelzine: Increased arterial pressure

Pindolol: Hypertension, then bradycardia

Practolol: Hypertension, then bradycardia

Propranolol: Hypertension, then bradycardia

Protriptyline: The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of epinephrine.

Rasagiline: Increased arterial pressure

Reserpine: Increased arterial pressure

Sotalol: Hypertension, then bradycardia

Timolol: Hypertension, then bradycardia

Tranylcypromine: Increased arterial pressure

Trimipramine: Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Epinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Venlafaxine: Venlafaxine may increase the tachycardic and vasopressor effects of epinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.