Adrenaline (Epinephrine)

Adrenaline, known in the United States and in pharmacology as epinephrine, is a catecholamine that acts both as a circulating hormone and as a neurotransmitter ^[1]. More than nine-tenths of the body's circulating supply is made and released by the adrenal medulla, the inner part of the adrenal glands that sit atop the kidneys, with smaller amounts produced by certain neurons ^[1]. Chemically it belongs to the same family as noradrenaline and dopamine, and it is the substance through which the body's own catecholamines engage a large group of cell receptors called adrenoceptors ^[1].

Adrenaline holds a notable place in the history of biochemistry as the first hormone to be isolated in pure form. Working in the United States, the Japanese chemist Jokichi Takamine crystallized it from the adrenal gland in 1900, an achievement that helped establish the modern concept of hormones ^[4]. Its structure was soon worked out and it was chemically synthesized within a few years, and it has been used medically for well over a century ^[4][1].

In medicine, adrenaline is best known as the emergency treatment for anaphylaxis, the rapid and potentially fatal systemic allergic reaction, where prompt injection into a muscle is the recommended first-line therapy ^[2]. It is also a mainstay of resuscitation during cardiac arrest, though large trials have sharpened understanding of its benefits and limits; a major randomized study found that it improved short-term survival after out-of-hospital cardiac arrest but did not clearly improve survival with a good neurological outcome ^[3]. Other uses include relieving the airway swelling of croup, prolonging local anesthesia by constricting nearby blood vessels, and managing certain kinds of severe bleeding and low blood pressure ^[1].

It is given by several routes depending on the situation, including intramuscular injection from pre-filled auto-injectors carried by people at risk of severe allergy, intravenous infusion in intensive care, and inhalation ^[2][1]. Adrenaline is an inexpensive, off-patent medicine available worldwide and is listed by the World Health Organization as an essential medicine, although the cost and availability of auto-injectors remain practical concerns in many countries ^[2].

Adrenaline auto-injectors are prescription; the drug is otherwise used by clinicians. In a true emergency its benefits far outweigh its risks, but its stimulant effects can cause a pounding heart, anxiety, tremor, headache, and pallor. Given too fast or in too high a dose, especially intravenously, it can trigger dangerous rhythm disturbances, severe hypertension, or strain the heart. Extra caution applies in older people and those with heart disease, though anaphylaxis is never a reason to withhold it. Accidental injection into a finger can cause intense local vasoconstriction. It degrades in light and heat, so devices must be replaced when expired or discolored.

The interaction most likely to be met in practice is with beta blockers. Non-selective agents such as propranolol block beta-mediated vasodilation and bronchodilation while leaving alpha-1 vasoconstriction untouched, so epinephrine can produce a severe hypertensive response with reflex bradycardia, and the bronchodilation wanted in anaphylaxis never arrives.

Halogenated hydrocarbon anesthetics sensitize the myocardium to catecholamines and make ventricular arrhythmia considerably likelier during epinephrine exposure. Digoxin, quinidine and thyroid hormone add to the same arrhythmic risk.

Monoamine oxidase inhibitors and tricyclic antidepressants potentiate the pressor effect, tricyclics by blocking neuronal reuptake of catecholamines, and hypertensive crisis has followed. Ergot alkaloids and oxytocin can do the same through additive vasoconstriction. Alpha blockers such as phentolamine and chlorpromazine pull in the opposite direction and blunt the pressor response.

None of this changes the calculus in anaphylaxis, where epinephrine has no substitute; it changes the response a clinician can expect and the complications that follow.

Checking a whole stack? Run it through interactions + stacks.