Amrinone. A preliminary review of its pharmacological properties and therapeutic use

Abstract

Amrinone is a bipyridine derivative with positive inotropic effects and vasodilatory properties. However, in the clinical setting of congestive heart failure, the relative contribution of these factors remains a matter of conjecture. Its mode of action appears to be related to alterations in extracellular and intracellular calcium balance, probably mediated by increased levels of tissue cyclic adenosine monophosphate and possibly involving a sodium-dependent pathway. Clinical experience has mostly been short term and is limited to a relatively small number of patients with severe congestive heart failure, refractory to conventional treatment. Amrinone rapidly improves cardiac performance by decreasing systemic vascular resistance (afterload), decreasing the determinants of left ventricular filling pressure (preload) and improving the cardiac contractility. Improvements in exercise performance and clinical symptomatology occur without an increase in heart rate or decrease in mean arterial pressure. Amrinone has been compared with dopamine, dobutamine, pirbuterol and prazosin in preliminary short terms studies in patients with severe congestive heart failure, although more studies are needed before any relative clinical advantages or disadvantages can be ascribed to amrinone. Initial experience suggests that the addition of vasodilators such as hydralazine and isosorbide dinitrate to amrinone therapy may confer additional haemodynamic benefits. Preliminary medium term studies suggest that tolerance to the haemodynamic effects of amrinone does not usually occur, but long term studies are needed to determine whether amrinone alters the normal progression of the disease and whether overall mortality is affected. Amrinone has usually been administered as intravenous bolus doses (totalling 1.5 to 3.6 mg/kg/day) and/or continuous intravenous infusion, with varied results. Generally, an oral dose greater than the intravenous dose is required to achieve an equivalent level of response. Reversible, usually asymptomatic, thrombocytopenia occurs in about 20% of patients treated with amrinone. Arrhythmias and gastrointestinal disturbances have been reported, but wider clinical experience is required to determine the side effect profile of the drug.