Drug information of Milrinone

Mechanism of effect

Milrinone, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle

Pharmacodynamic

Milrinone, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle. This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle. Additional experimental evidence also indicates that milrinone is not a beta-adrenergic agonist nor does it inhibit sodium-potassium adenosine triphosphatase activity as do the digitalis glycosides

Pharmacokinetics

Following intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients, milrinone had a volume of distribution of 0.38 liters/kg, a mean terminal elimination half-life of 2.3 hours, and a clearance of 0.13 liters/kg/hr. Milrinone has been shown (by equilibrium dialysis) to be approximately 70% bound to human plasma protein. The primary route of excretion of milrinone in man is via the urine. The major urinary excretions of orally administered milrinone in man are milrinone (83%) and its 0-glucuronide metabolite (12%). Elimination in normal subjects via the urine is rapid. The mean renal clearance of milrinone is approximately 0.3 liters/min, indicative of active secretion.

Drug indications

the short-term intravenous treatment of patients with sever heart failure , acute decompensated heart failure after heart surgery

Dosage

Usual Adult Dose for Congestive Heart Failure Loading dose: 50 mcg/kg IV over 10 minutes. Maintenance infusion: 0.375 to 0.75 mcg/kg/min Usual Pediatric Dose for Congestive Heart Failure less than 1 month: Hemodynamic support: Full term neonates: Loading dose: 50 to 75 mcg/kg IV administered over 15 minutes followed by a continuous infusion of 0.5 mcg/kg/minute; titrate to effect; range: 0.25 to 0.75 mcg/kg/minute has been used by several centers 1 month and older: Loading dose: 50 mcg/kg IV over 15 minutes. Maintenance infusion: 0.25-1 mcg/kg/min

Drug contraindications

hypersensitivity to drug or its components.

Side effects

Headache , chest pain , rash , hypotension , thrombocytopenia , Tremor , Hypokalemia , Anaphylactic reaction , ventricular arrhythmias

Interactions

Spironolactone , insulin , isosorbide dinitrate , Potassium chloride , Diazepam , Furosemide , Captopril , Quinidine , Lidocaine , Nitroglycerin , Heparin , Hydralazine , Hydrochlorothiazide , Warfarin

Alerts

1-Whether given orally or by continuous or intermittent intravenous infusion, milrinone has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure. In a multicenter trial of 1088 patients with Class III and IV heart failure, long-term oral treatment with milrinone was associated with no improvement in symptoms and an increased risk of hospitalization and death. In this study, patients with Class IV symptoms appeared to be at particular risk of life-threatening cardiovascular reactions. There is no evidence that milrinone given by long-term continuous or intermittent infusion does not carry a similar risk. 2-The use of milrinone both intravenously and orally has been associated with increased frequency of ventricular arrhythmias, including nonsustained ventricular tachycardia. Long-term oral use has been associated with an increased risk of sudden death. Hence, patients receiving milrinone should be observed closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias 3-Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis.

Points of recommendation

1-During therapy with milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure 2-Cases of infusion site reaction have been reported with intravenous milrinone therapy

Pregnancy level

C

Related drugs

Digoxin