Compare and contrast the pharmacology of noradrenaline and dobutamine.
The best answers used tables and key pharmacological headings for comparisons, and
avoided long sentences/ paragraphs.
An answer that correctly considered the following sections would be awarded a very good
pass: Presentation, pharmacodynamics, mechanism of action, organ effects, side effects and
Many candidates failed to identify agents as natural / synthetic catecholamines.
Few answers correctly mentioned the available preparations of these drugs or considered the
structure activity relationships. Only 3 candidates commented that dobutamine is a racemic
Intracellular second messenger pathways were often incorrectly recounted or not mentioned at
all. Pharmacodynamic effects on all organ systems, and all CVS parameters (HR, inotropy,
PVR, SVR, SBP/DBP/MAP, regional circulations) should be considered. Metabolic fate and
clinical dosage ranges were frequently incorrectly quoted.
For all their complaining, the examiners passed almost everybody (84% of the candidates scored more than 5.0).
|Chemistry||Endogenous catecholamine||Synthetic catecholamine|
|Routes of administration||IV||IV|
|Absorption||Basically zero oral availability due to destruction by brush border enzymes in the gut (COMT and MAO)||Basically zero oral availability due to destruction by brush border enzymes in the gut (COMT and MAO)|
|Solubility||pKa = 8.85; water-soluble||pKa = 10.14; sparingly soluble in water|
|Distribution||VOD = 0.12 L/kg, i.e. essentially confined to the circulating volume; 25% protein-bound||VOD = 0.2 L/kg, i.e. essentially confined to the circulating volume. Protein binding is unknown- presumably, minimal|
|Target receptor||Noradrenaline is highly selective for the alpha-1 receptor||Dobutamine is a racemic mixture of stereoisomers; net effect is a partial alpha-1 agonist effect, a full beta-1 agonist effect, and a weak beta-2 agonist effect|
|Metabolism||Metabolised rapidly and completely by COMT and MAO||Metabolised rapidly and completely by COMT and MAO|
|Elimination||Metabolites are renally excreted. Half-life is ~2 minutes||Metabolites are renally excreted. Half-life is ~2 minutes|
|Time course of action||Very short acting, very rapid onset of effect||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.||By binding to the beta-1 receptor, dobutamine causes an increase in intracellular cAMp, which leads to increased calcium availability inside the cardiac myocytes, and therefore increased contractility and pacemaker automaticity|
|Clinical effects||Increased peripheral resistance, increased afterload, increased blood pressure; redistribution of blood flow from splanchnic circulation and skeletal muscle.||Increased heart rate, increased contractility, increased lusitopy; decreased peripheral vascular resistance due to beta-2 effect|
|Single best reference for further information||TGA PI document||TGA PI document|
von Euler, Ulf Svante. "Noradrenaline." (1956): 349.
RUFFOLO Jr, ROBERT R. "The pharmacology of dobutamine." The American journal of the medical sciences 294.4 (1987): 244-248.
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.
Ruffolo Jr, Robert R., and Karen Messick. "Systemic hemodynamic effects of dopamine,(±)-dobutamine and the (+)-and (−)-enantiomers of dobutamine in anesthetized normotensive rats." European journal of pharmacology 109.2 (1985): 173-181.