Question 12

Outline the pharmacology of noradrenaline.

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College Answer

Candidates should expect that questions relating to “the pharmacology of ……” are likely to
be common. Thus candidates should have prepared structured approach for any such
question. For example, one that includes predefined major categories such as
pharmacodynamics and pharmacokinetics and sub-categories such as mechanism of action,
absorption, preparations, bioavailability, volume of distribution, metabolism, elimination,
adverse effect, clinical indications, precautions/interactions, etc. and the information relevant
to each category. Failure to take a structured approach to such questions, as was observed
amongst some candidates within this exam, risks omission of vital facts (and not gaining
marks) and errors. Noradrenaline is such a common drug within intensive care practice and
so candidates would be expected to know it in great detail. There are many references for it,
such as the ones listed below.
Syllabus – G3a, 2b
References – Goodman and Gillman Chp 10 and Katzung.

Discussion

Class Vasopressor
Chemistry Catecholamine
Routes of administration IV
Absorption Basically zero oral availabilty due to destruction by brush border enzymes in the gut (COMT and MAO)
Solubility pKa = 8.85; water-soluble
Distribution VOD = 0.12 L/kg, i.e. essentially confined to the circulating volume; 25% protein-bound
Target receptor Noradrenaline is highly selective for the alpha-1 receptor
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, noradrenaline 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.
Clinical effects Increased peripheral resistance, increased afterload, increased blood pressure; redistribution of blood flow from splanchnic circulation and skeletal muscle.
Single best reference for further information TGA PI document

References

Natalini, Giuseppe, et al. "Norepinephrine and metaraminol in septic shock: a comparison of the hemodynamic effects." Intensive care medicine 31.5 (2005): 634-637.

von Euler, Ulf Svante. "Noradrenaline." (1956): 349.

Smith, K. Shirley, and A. Guz. "L-Noradrenaline in treatment of shock in cardiac infarction." British medical journal 2.4850 (1953): 1341.

Rokyta Jr, Richard, et al. "The effects of short-term norepinephrine up-titration on hemodynamics in cardiogenic shock." Physiol Res 59.3 (2010): 373-8.