Milrinone Lactate (milrinone lactate)

Milrinone lactate, a selective phosphodiesterase (PDE) inhibitor, is a positive inotropic agent that has vasodilating effects.

Milrinone lactate is a structural analog of inamrinone (no longer commercially available in the US); however, the drug differs structurally from other inotropic agents (e.g., cardiac glycosides, catecholamines). Milrinone, a selective phosphodiesterase (PDE) inhibitor, is a positive inotropic agent that also has vasodilating effects.

The mechanism(s) for milrinone's effect on myocardial contraction differs from those of other inotropic agents (e.g., cardiac glycosides, catecholamines, beta-adrenergic blocking agents). Although the exact mechanism(s) of action has not been fully elucidated, milrinone selectively inhibits cyclic adenosine monophosphate (cAMP) phosphodiesterase activity in cardiac and vascular muscles resulting in increased intracellular concentrations of cAMP. Such increased concentrations of cAMP may be associated with increases in intracellular ionized calcium resulting in augmentation of calcium influx to the contractile proteins which result in increased myocardial contractility.

In addition to its inotropic effects, milrinone has vasodilatory activity; however, the drug has little chronotropic activity. Milrinone appears to act directly on vascular smooth muscle as demonstrated by dose- and plasma concentration-related increases in forearm blood flow in patients with congestive heart failure (CHF). Unlike cardiac glycosides, milrinone does not inhibit sodium-potassium-activated adenosine triphosphatase activity; the drug's inotropic effect does not appear to be associated with beta-adrenergic agonist activity.

The inotropic and vasodilatory effects of milrinone have been observed in patients with therapeutic milrinone concentrations of 100-300 ng/mL. Studies in healthy individuals and patients with CHF indicate that milrinone produces substantial improvements in cardiac output, capillary wedge pressure, and vascular resistance, while the drug is associated with minor changes in heart rate or myocardial oxygen consumption. Milrinone exhibits favorable inotropic effects in fully digitalized patients without causing signs of cardiac toxicity.

In patients with CHF, IV milrinone produces dose-related increases in the peak rate of left ventricular pressure rise (dp/dt) and improves diastolic function, as evidenced by enhancement in left ventricular diastolic relaxation. Improvement of left ventricular function occurs without development of symptoms or electrocardiographic (ECG) signs of myocardial ischemia. In healthy individuals, milrinone produces increases in the slope of the left ventricular pressure-dimension relationship, indicating a direct inotropic effect of the drug.

Milrinone-induced hemodynamic effects usually begin within 5-15 minutes following IV administration of the drug. Plasma concentrations of milrinone appear to correlate with its cardiovascular effects. Milrinone-induced hemodynamic responses usually are maintained during continuous IV infusion for 48-72 hours; no evidence of tachyphylaxis has been observed.

In patients with CHF, the elimination half-life of IV milrinone is about 2.4 hours and clearance is 2.3 mL/minute per kg. In patients with renal impairment, the elimination half-life is substantially increased and dosage adjustment is recommended. (See Dosage and Administration: Special Populations.) Milrinone is excreted principally in urine; only small amounts are excreted in feces. In healthy individuals, approximately 83 and 12% of a dose is excreted in urine as unchanged drug and its O-glucuronide metabolite, respectively.

Urinary excretion is rapid; after dosing, about 60% of a dose is recovered within 2 hours and about 90% is recovered within 8 hours.

USES: This medication is used for the short-term treatment of heart failure. It works by making your heart beat stronger and by relaxing certain blood vessels so that the amount of blood that is pumped from the heart is increased. This effect may help with symptoms of heart failure (such as shortness of breath, tiredness).

Generic name: milrinone lactate
Pronunciation: (MIL-ri-none)
Drug class: Inotropic Agents
Therapeutic class: Cardiovascular Therapy Agents

The following indications are listed for Milrinone Lactate:

• Acute Decompensated Heart Failure

Also known as: Acute Heart Failure, Overt Cardiac Failure, Overt Chf, Overt Congestive Heart Failure, Overt Heart Failure, Uncontrolled Cardiac Failure.