Amrinone
Mechanism :
Amrinone is a positive inotropic agent with vasodilatory activity, different in structure and mode of action from either digitalis glycosides or catecholamines. Its mechanism of action has not been fully elucidated. It inhibits myocardial cyclic adenosine monophosphate phosphodiesterase (c-AMPase) activity and increases cellular levels of c-AMP. Unlike digoxin, it does not inhibit sodium-potassium adenosine tri-phosphatase activity. Vasodilatory effect of amrinone is the result of direct relaxant effect on vascular smooth muscle. The drug reduces both the afterload and preload.
Indication :
- Short-term management of severe congestive heart failure
Contraindications :
In patients with hypersensitivity to amrinone or sensitivity to bisulfites.
Dosing :
Loading dose of 0.75 mg/kg IV infused over 3-5 minutes, followed by a maintenance infusion of 3-5 mcg/kg/min IV in <28 days old and 5-15 mcg/kg/min IV in children >28 days of age; Bolus dose may be repeated after 30 minutes to maintain a therapeutic dosage range of 0.5-7 mcg/mL. Maximum daily dose is 10 mg/kg.
Renal Adjustment:
If Creatinine Clearance is >30 ml/min, no dose adjustment required.
If Creatinine Clearance is 10-29 mL/min, reduce dose by 50%.
If Creatinine Clearance is <10 mL/min, reduce dose by 75%.
Adverse Effect :
Thrombocytopenia, nausea, vomiting, abdominal pain, anorexia, diarrhea, ventricular tachycardia, ventricular fibrillation, ventricular ectopy, atrial flutter, bradycardia, hypotension, hypersensitivity reactions.
Interaction :
No specific drug interaction study has been done in humans with injectable amrinone.
Amrinone has been used concurrently with the following drugs: digitalis glycosides, quinidine, propranolol, metoprolol, prazosin, hydralazine, captopril, isosorbide dinitrate, nitroglycerin, lidocaine, furosemide, ethacrynic acid, hydrochlorothiazide, chlorthalidone, spironolactone, potassium supplements, insulin, heparin, warfarin sodium and diazepam. No serious adverse effects due to the interaction between these drugs and amrinone were reported. However, careful dosage readjustments of concurrent medication may be required.
Chemical Interactions: A chemical interaction occurs slowly over a 24-hour period when the IV solution of amrinone is mixed directly with dextrose (glucose)-containing solutions. Therefore, amrinone injection should not be diluted with solutions that contain dextrose (glucose) prior to injection.
A chemical interaction occurs by the formation of a precipitate when furosemide is injected into an IV line of an infusion of amrinone. Therefore, furosemide should not be administered in IV lines containing amrinone.
Hepatic Dose :
It is metabolised in the liver. Elimination is reduced. Thus, dosage adjustment may be required.