Compare and contrast the pharmacology of adrenaline and milrinone.
This question was best answered using a table. Better answers included: the mechanisms of
action, the pharmacokinetics and pharmacodynamics, indications for use and adverse effects.
To complete the answer, the two drugs should have been compared and contrasted. There
are many areas which could be contrasted e.g. different indications, different mechanisms of
action, different half-lives and duration of action, different metabolism and different
pharmacodynamic effects, in particular the effects on the cardiovascular system and the
pulmonary circulation. Similarities should also have been highlighted
|Routes of administration||IV, IM, subcutaneous, nebulised, topical, as eye drops and directly into the ETT during an arrest||IV; but can also be administed as a nebulised aerosol, and had initially been marked as an oral preparation|
|Absorption||Basically zero oral availabilty due to destruction by brush border enzymes in the gut (COMT and MAO)||Well absorbed orally; 92% oral bioavailability|
|Solubility||pKa of 9.69; minimal water slubility||pKa 4.6 and 8.5; good solublity at physiological pH|
|Distribution||VOD = 0.1-0.2 L/kg; 12% protein-bound||0.38L/kg; 70% protein bound|
|Target receptor||All adrenoceptors, with some selectivity for beta-1 and beta-2 at lower doses||Phosphodiesterase 3|
|Metabolism||Metabolised rapidly and completely by COMT and MAO||Mostly cleared renally; of the free fraction some undergoes hepatic metabolism into an inactive o-glucouronide, and the rest is excreted unchanged at a rate which varies depending on renal blood flow|
|Elimination||Metabolites are renally excreted. Half-life is ~2 minutes||Half life is 2.3 hours in patients with heart failure, slightly less in normal healthy adults and longer in patients with renal dysfunction|
|Time course of action||Very short acting, very rapid onset of effect||Onset of action is usually within 5-15minutes|
|Mechanism of action||By binding to the alpha-1 receptor, adrenaline 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 beta-1 and beta-2 receptors, it increases cAMP, whcih as a second messenger mediates the other cardiovascular clinical effects||Increases cyclic AMP by inhibiting phosphodiesterase 3, which is responsible for cAMP catabolism. Selective for vascular smooth muscle and cardiac muscle.|
|Clinical effects||Increased cardiac contractility, increased heart rate, some peripheral vasodilation, decreased afterload, hyperglycaemia, hyperlactataemia, hypokalemia, increased arrhythmogenicity||Improved ventricular contractility; decreased systemic vascular resistance; decreased pulmonary vascular resistance; tachycardia; propensity to arrhythmias.|
|Single best reference for further information||TGA PI document||Canadian (Novopharm) product pamphlet for milrinone lactate|
Gorain, Bapi, et al. "Pharmacology of Adrenaline, Noradrenaline, and Their Receptors." Frontiers in Pharmacology of Neurotransmitters. Springer, Singapore, 2020. 107-142.
Stroshane, Ronald M., et al. "Oral and intravenous pharmacokinetics of milrinone in human volunteers." Journal of pharmaceutical sciences 73.10 (1984): 1438-1441.
Alousi, A. A., and D. C. Johnson. "Pharmacology of the bipyridines: amrinone and milrinone." Circulation 73.3 Pt 2 (1986): III10.