Compare and contrast the pharmacology of metaraminol and noradrenaline
Marks were distributed across pharmaceutics, uses, dose & administration, mechanism of action,
Pharmacokinetcs and Pharmacodynamics. Common omissions were doses/rates of infusion,
effects other than on heart/SVR (e.g. splanchnic, renal blood flow), indirect effect of metaraminol,
receptor effect of noradrenaline other than alpha 1 and tachyphylaxis.
Considering just how difficult it was to find any information about the pharmacokinetics of metaraminol, it is remarkable that 71% of trainees were able to pass this SAQ.
|Routes of administration||IV, s/c, IM||IV|
|Dose||0.5mg boluses||Infusion (typical dose range 001-0.5 μg/kg/hr)|
|Absorption||Good oral bioavailability (enough for oral administration to be feasible)||Basically zero oral availability due to destruction by brush border enzymes in the gut (COMT and MAO)|
|Solubility||pKa 8.79; excellent water solubility||pKa = 8.85; water-soluble|
|Distribution||VOD = 4L/kg; 45% protein bound. Distributes into catecholamine storage vesicles, where it persists for days.||VOD = 0.12 L/kg, i.e. essentially confined to the circulating volume; 25% protein-bound|
|Target receptor||Directly acts on alpha-1 and beta-1 receptors||Noradrenaline is highly selective for the alpha-1 receptor|
|Metabolism||Not metabolised, it seems (not susceptible to COMT or MAO)||Metabolised rapidly and completely by COMT and MAO|
|Elimination||Eliminated slowly over hours/days. Distribution half-life is rapid(minutes).||Metabolites are renally excreted. Half-life is ~2 minutes|
|Time course of action||Effect lasts 20-60 minutes. Tachyphylaxis develops with sustained infusion||Very short acting, very rapid onset and offset of effect. No tachyphylaxis.|
|Mechanism of action||By acting as a false neurotransmitter, metaraminol displaces noradrenaline from storage vesicles in noradrenergic synapses, therefore increasing the synaptic and systemic noradrenaline concentration. Its main effects are therefore the same as the effects of noradrenaline.||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.|
As metaraminol mainly exerts its effects by stimulating release of noradrenaline, the effects of metaraminol are the same as the effects of noradrenaline: increased peripheral resistance, increased afterload, increased blood pressure; redistribution of blood flow from splanchnic circulation and skeletal muscle. Compensatory decrease in heart rate and cardiac output.
|Single best reference for further information||PubChem||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.