Compare and contrast the pharmacology of EPHEDRINE and METARAMINOL.
The 'compare and contrast' pharmacology question indicates the use of a standardised structure that incorporates pharmaceutics, pharmacokinetics and pharmacodynamics. The best answers provided excellent detail, ie. precise descriptions of mechanisms of action and emphasised noteworthy areas of contrast between the two drugs. Highlighting opportunities for use and areas of caution/drug limitations. Overall, most candidates seemed to have a sufficient knowledge of metaraminol but details surrounding ephedrine were often lacking
| Name | Metaraminol | Ephedrine |
| Class | Vasopressor | Inotrope |
| Chemistry | Phenylethylamine | Phenylethylamine |
| Routes of administration | IV, s/c, IM | IV, s/c, IM |
| Absorption | Good oral bioavailability (enough for oral administration to be feasible) | Good oral bioavailability (88%) |
| Solubility | pKa 8.79; excellent water solubility | pKa = 10.25; highly water soluble, but also reasonably lipid soluble, so it crosses the blood brain barrier |
| Distribution | VOD = 4L/kg; 45% protein bound. Distributes into catecholamine storage vesicles, where it persists for days. | VOD=3L:/kg, minimally protein-bound (~4-6%) |
| Target receptor | Directly acts on alpha-1 and beta-1 receptors, but this is not the main mechanism of effect | Directly acts on beta-1 receptors, but this is not the main mechanism of effect |
| Metabolism | Not metabolised, it seems (not susceptible to COMT or MAO) | A small and variable quanmity is metabolised into norephedrine, but otherwise it is eliminated unchanged |
| Elimination | Eliminated slowly over hours/days. Distribution half-life is rapid(minutes). | Mostly eliminated as unchanged drug in the urine |
| Time course of action | Effect lasts 20-60 minutes | Average half-life is about 6 hours |
| 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 acting as a false neurotransmitter, ephedrinel displaces noradrenaline from storage vesicles in noradrenergic synapses, therefore increasing the synaptic and systemic noradrenaline concenttration. Because it has effects on all classes of noradrenaline receptor, the clinical effect is similar to adrenaline. |
| Clinical effects | 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. | Increased peripheral resistance, increased afterload, increased blood pressure; redistribution of blood flow from splanchnic circulation and skeletal muscle. Increased heart rate, contractility, and cardiac output. |
| Single best reference for further information | PubChem | Limberger et al (2013) |
Limberger, Renata Pereira, et al. "Pharmacological Effects of Ephedrine 38." (2013).
HARRISON, DONALD C., CHARLES A. CHIDSEY, and EUGENE BRAUNWALD. "Studies on the mechanism of action of metaraminol (Aramine)." Annals of internal medicine 59.3 (1963): 297-305.
Livesay, W. R., John H. Moyer, and Don W. Chapman. "The cardiovascular and renal hemodynamic effects of Aramine." American heart journal 47.5 (1954): 745-756.