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.
|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.