From the Guidelines
Epinephrine acts on alpha-1, beta-1, and beta-2 adrenergic receptors. The therapeutic actions of epinephrine include increased vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema via α1-adrenergic agonist receptor effects, increased inotropy and increased chronotropy via β1-adrenergic receptor agonist effects, and bronchodilation and decreased release of mediators of inflammation from mast cells and basophils via β2-adrenergic receptor agonist effects 1.
Key Receptor Effects
- Alpha-1 (α1) receptors: vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema
- Beta-1 (β1) receptors: increased inotropy and increased chronotropy
- Beta-2 (β2) receptors: bronchodilation and decreased release of mediators of inflammation from mast cells and basophils
The most recent and highest quality study, published in 2019, supports the use of epinephrine in cardiac arrest, with improved survival to hospital discharge and admission, as well as increased return of spontaneous circulation (ROSC) 1.
Clinical Implications
- In anaphylaxis, epinephrine's alpha-1 effects help restore blood pressure through vasoconstriction, while its beta-2 effects relieve bronchospasm
- In cardiac arrest, epinephrine's beta-1 effects increase heart contractility and rate
- The receptor profile explains why epinephrine's effects are dose-dependent, with lower doses causing vasodilation and higher doses causing vasoconstriction
Overall, epinephrine's actions on alpha-1, beta-1, and beta-2 adrenergic receptors make it a crucial medication in various clinical scenarios, including anaphylaxis and cardiac arrest.
From the FDA Drug Label
Epinephrine acts on both alpha (α)- and beta (β)-adrenergic receptors. The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction. Decreases in systemic vascular resistance and diastolic blood pressure are observed at low doses of epinephrine because of β2-mediated vasodilation, but are overtaken by α1-mediated peripheral vasoconstriction at higher doses leading to increase in diastolic blood pressure Epinephrine acts on alpha (α) and beta (β) adrenergic receptors, including:
- α1 receptors, which mediate peripheral vasoconstriction
- β2 receptors, which mediate vasodilation 2
From the Research
Adrenergic Receptors and Epinephrine
Epinephrine acts on various adrenergic receptors, including:
- Alpha 1 (α1) receptors: found in smooth muscle cells of blood vessels and urinary tract, inducing constriction 3
- Alpha 2 (α2) receptors: found in the central nervous system, decreasing arterial blood pressure 4, 5, 3
- Beta 1 (β1) receptors: predominantly found in the heart, inducing positive inotropic and chronotropic effects 3
- Beta 2 (β2) receptors: distributed extensively throughout the body, activating adenylyl cyclase, dilating blood vessels and bronchioles, and relaxing muscles of the uterus, bladder, and gastrointestinal duct 3, 6
Receptor Specificity and Tissue Distribution
Epinephrine stimulates all subtypes of α and β adrenoreceptors 3. The receptor specificity of epinephrine is as follows:
- α1 and α2 receptors: involved in vasoconstriction and decreased arterial blood pressure, respectively 7, 4
- β1 receptors: involved in cardiac stimulation and positive inotropic effects 7, 3
- β2 receptors: involved in vasodilation, bronchodilation, and relaxation of smooth muscles 7, 3, 6
Physiological Effects of Epinephrine
The physiological effects of epinephrine are mediated through its action on adrenergic receptors, including: