Which of the following is the best inotrope agent for use in Right Hea Failure Secondary to pulmonary hypeension-
Correct Answer: Milrinone
Description: Milrinone, commonly known and marketed under the brand name Primacor, is a medication used in patients who have hea failure. It is a phosphodiesterase 3 inhibitor that works to increase the hea's contractility and decrease pulmonary vascular resistance. Milrinone also works to vasodilate which helps allete increased pressures (afterload) on the hea, thus improving its pumping action. While it has been used in people with hea failure for many years, studies suggest that milrinone may exhibit some negative side effects that have caused some debate about its use clinically Overall, milrinone suppos ventricular functioning of the hea by decreasing the degradation of cAMP and thus increasing phosphorylation levels of many components in the hea that contribute to contractility and hea rate. Milrinone use following cardiac surgery has been under some debate because of the potential increase risk of postoperative atrial arrhythmias.] However, in the sho term milrinone has been deemed beneficial to those experiencing hea failure and an effective therapy to maintain hea function following cardiac surgeries. There is no evidence of any long term beneficial effects on survival.In critically ill patients with evidence of cardiac dysfunction there is limited good quality evidence to recommend its use Cyclic adenosine monophosphate (cAMP) causes increased activation of protein kinase A (PKA). PKA is an enzyme that phosphorylates many elements of the contractile machinery within the hea cell. In the sho term this leads to an increased force of contraction. Phosphodiesterases are enzymes responsible for the breakdown of cAMP. Therefore, when phosphodiesterases lower the level of cAMP in the cell they also lower the active fraction of PKA within the cell and reduce the force of contraction. Milrinone is a phosphodiesterase-3 inhibitor. This drug inhibits the action of phosphodiesterase-3 and thus prevents degradation of cAMP. With increased cAMP levels there is an increase in the activation of PKA. This PKA will phosphorylate many components of the cardiomyocyte such as calcium channels and components of the myofilaments. Phosphorylation of calcium channels permits an increase in calcium influx into the cell. This increase in calcium influx results in increased contractility. PKA also phosphorylates potassium channels promoting their action. Potassium channels are responsible for repolarization of the cardiomyocytes therefore increasing the rate at which cells can depolarize and generate contraction. PKA also phosphorylates components on myofilaments allowing actin and myosin to interact more easily and thus increasing contractility and the inotropic state of the hea. Milrinone allows stimulation of cardiac function independently of b-adrenergic receptors which appear to be down-regulated in those with hea failure. Ref Davidson 23rd edition pg 467
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