At low doses, epinephrine preferentially binds to beta 1 and beta 2 receptors, causing increased cardiac output from the heart and bronchodilation in the airways. At high doses, epinephrine binds to alpha-1 receptors, which cause systemic vasoconstriction and an increase in blood pressure. Clinically, epinephrine is commonly used to treat anaphylaxis and cardiac arrest. It can also be used to treat open angle glaucoma with a variety of mild ocular side effects.

Key Points

  • Epinephrine
    • For context, endogenous epi: secreted by adrenal medulla in a mix of 80% epinephrine, 20% norepinephrine directly into the bloodstream to amplify sympathetic nervous system activity.
    • Mechanism of Action
      • Beta 1 and 2 Agonist > Alpha Agonist
        • Beta-1 and 2 receptors have higher affinity for epinephrine but get saturated quickly. At high doses, alpha-1 activity takes over.
        • Epinephrine released by the adrenal medulla acts on adrenergic receptors in the heart, lungs, liver, and skeletal muscle to increase sympathetic tone and mediate the acute stress response.
        • Beta 1 Agonist
          • Increased HR, contractility, and AV nodal conduction → Increased Cardiac Output
        • Beta 2 Agonist
          • Bronchodilation and vasodilation (mild)
        • Alpha 1 Activation
          • Alpha effects predominant at high doses
          • Vasoconstriction causes increased vascular resistance and blood pressure
          • Decreased aqueous humor production
          • Note: taking beta-blocker can lead to unopposed alpha-adrenergic effects
    • Clinical Use
      • Anaphylaxis
        • Bronchodilation via Beta 2 addresses bronchospasm
        • Vasoconstriction via Alpha 1 addresses distributive shock
      • Asthma
        • Bronchodilation via Beta 2 effect
      • Open-Angle Glaucoma
        • Decreased aqueous humor production from vasoconstriction via Alpha 1 effect
      • Cardiac Arrest
        • Vasoconstriction via alpha 1 effect leads to higher diastolic pressure, increasing coronary and systemic perfusion. This increases chance of ROSC, and helps keep the tissues alive longer
        • Epi + amio are part of ACLS - basically if a person has a shockable rhythm, but remains pulseless, you will do epi boluses in conjunction with CPR. It’s a part of “codes”
        • Epinephrine increases arterial blood pressure and coronary perfusion during CPR via alpha-1-adrenoceptor agonist effects
        • The alpha effects cause peripheral vasoconstriction, which in turn leads to increased blood flow in the central circulation, improving perfusion of the heart and brain. These effects are potentially beneficial, and have been hypothesized to increase the likelihood of return of spontaneous circulation (ROSC) among cardiac arrest patients
      • Hypotension
        • Increased Cardiac Output due to Beta 1 effect → Increased BP
        • Vasoconstriction due to Alpha 1 effect → Increased BP
    • Adverse Effects
      • Ocular Side Effects: Mydriasis (explains contraindication to Closed-Angle Glaucoma), Blurry Vision, Ocular Hyperemia, Foreign Body Sensation, Ocular allergic reactions, ocular pruritus
      • Increases glucose availability
        • Epinephrine (and norepinephrine to a lesser extent) increases hepatic and renal glycogenolysis and gluconeogenesis; it also increases the release of gluconeogenic substrates from muscle and fat.
        • Epinephrine from the adrenals increases glucose by multiple mechanisms, including increased glycogenolysis and gluconeogenesis in the liver and decreased glucose uptake by skeletal muscle. Epinephrine also causes increased alanine release from skeletal muscle, which serves as a source of gluconeogenesis in the liver. In adipose tissue, epinephrine increases the breakdown of triglycerides, thereby increasing circulating free fatty acids and glycerol that can be utilized as gluconeogenic substrates.