Question 1

Describe the pharmacology of adrenaline.

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College Answer

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.

Discussion

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

References

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.