Describe the pharmacology of adrenaline.
Adrenaline is a level 1 drug and is commonly used in intensive care. A comprehensive explanation of the drugs MOA, PK, PD and side effect were expected. Candidates who scored well generally provided a factually accurate, detailed and well-structured answer. Overall, the quality of answer provided for this question was of a high standard.
| Name | Adrenaline |
| Class | Inodilator |
| Chemistry | Endogenous catecholamine |
| Routes of administration | IV, IM, subcutaneous, nebulised, topical, as eye drops and directly into the ETT during an arrest |
| Absorption | Basically zero oral availabilty due to destruction by brush border enzymes in the gut (COMT and MAO) |
| Solubility | pKa of 9.69; minimal water slubility |
| Distribution | VOD = 0.1-0.2 L/kg; 12% protein-bound |
| Target receptor | All adrenoceptors, with some selectivity for beta-1 and beta-2 at lower doses |
| Metabolism | Metabolised rapidly and completely by COMT and MAO |
| Elimination | Metabolites are renally excreted. Half-life is ~2 minutes |
| Time course of action | Very short acting, very rapid onset of effect |
| Mechanism of action | By binding to the alpha-1 receptor, adrenaline increases the release of a secondary messenger (inositol triphosphate, IP3) which results in the release of calcium into the cytosol, and thus enhanced smooth muscle contractility. By binding to beta-1 and beta-2 receptors, it increases cAMP, whcih as a second messenger mediates the other cardiovascular clinical effects |
| Clinical effects | Increased cardiac contractility, increased heart rate, some peripheral vasodilation, decreased afterload, hyperglycaemia, hyperlactataemia, hypokalemia, increased arrhythmogenicity |
| Single best reference for further information | TGA PI document |
Gorain, Bapi, et al. "Pharmacology of Adrenaline, Noradrenaline, and Their Receptors." Frontiers in Pharmacology of Neurotransmitters. Springer, Singapore, 2020. 107-142.
Stratton, JOHN R., et al. "Hemodynamic effects of epinephrine: concentration-effect study in humans." Journal of Applied Physiology 58.4 (1985): 1199-1206.
Lands, AoM, et al. "Differentiation of receptor systems activated by sympathomimetic amines." Nature 214.5088 (1967): 597-598.