Outline the pharmacology of noradrenaline.
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.
| 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 |
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.