An intravenous agent.

A phosphodiesterase 3 inhibitor that increases cardiac inotrophy, and peripheral vasodilatation.

Bioavailability is 100% as IV bolus or infusion.

Protein binding 70 to 80%.

Hepatic metabolism at 12%.

Biological half-life 2.3 hours

Excretion is by urine with 85% as unchanged drug within 24 hours.

Trade name Primacor.

Used in patients who have heart failure as a phosphodiesterase 3 inhibitor that works to increase the heart’s contractility and decrease pulmonary vascular resistance.

Works to vasodilate and alleviate increased pressures on the heart, thus improving its pumping action.

Overall supports ventricular functioning of the heart by decreasing the degradation of cAMP and thus increasing phosphorylation levels of many components in the heart that contribute to contractility and heart rate.

Associated with potential increase risk of postoperative atrial arrhythmias.

Short term benefits in patients experiencing heart failure and an effective therapy to maintain heart function following cardiac surgery, but no evidence of any long term beneficial effects on survival.

Calcium permits myosin and actin to interact which allows initiation of contraction within the cardiomyocytes, and with heart failure there may be a decreased amount of calcium within the cardiomyocytes reducing the available calcium to initiate contraction.

Cyclic adenosine monophosphate (cAMP) causes increased activation of protein kinase A (PKA), an enzyme that phosphorylates many elements of the contractile machinery within the heart cell.

Cyclic adenosine monophosphate (cAMP) associated with an increased force of contraction.

Phosphodiesterases are enzymes responsible for the breakdown of cAMP, and they also lower the active fraction of PKA within the cell and reduce the force of contraction.

Drug is a phosphodiesterase-3 inhibitor preventing degradation of cAMP.

With increased cAMP levels there is an increase in the activation of protein kinase A (PKA).

This PKA will phosphorylate many components of the cardiomyocyte such as calcium channels and components of the myofilaments, permiting an increase in calcium influx into the cell.

Increases in calcium influx permits increased contractility.

Protein kinase A (PKA) also phosphorylates potassium channels promoting their action.

Potassium channels are responsible for repolarization of the cardiomyocytes thereby increasing the rate at which cells can depolarize and generate contraction.

Protein kinase A (PKA) also phosphorylates components on myofilaments allowing actin and myosin to interact more easily and thus increasing contractility and the inotropic state of the heart.

Milrinone allows stimulation of cardiac function independently of β-adrenergic receptors which appear to be down-regulated in those with heart failure.

Its use may present potential adverse side effects in heart failure patients.

In the PROMISE trial there was a 28% increase in all-caused mortality in patients receiving oral milrinone compared to placebo in patients with chronic severe heart failure.

Use may be associated with increase atrial fibrillation following cardiac surgery.

Is associated with a 3-fold increase in tachyarrhythmias following surgery for congenital heart disease.

In patients with stage D heart failure with a history of ventricular tachyarrhythmias the use of milrinone was associated with more ICD shock treatments, without a significant difference in survival.
In patients with end-stage heart failure there is a significant increase in survival compared to historical controls.

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