Increasing the force of contraction of the heart (positive inotropic activity) is very important for most heart failure patients. There are several mechanisms by which this could be achieved. Cardiac steroids are perhaps the most useful and are being discussed here. Phosphodiesterase inhibitors, such as amrinone and milrinone, have also been explored and so are direct adenylate cyclase stimulants, such as forskolin. These drugs all act by affecting the availability of intracellular Ca+2 for myocardial contraction or increasing the sensitivity of myocardial contractile proteins.
The cardiac glycosides are an important class of naturally occurring drugs whose actions include both beneficial and toxic effects on the heart. Plants containing cardiac steroids have been used as poisons and heart drugs at least since 1500 B.C. Throughout history these plants or their extracts have been variously used as arrow poisons, emetics, diuretics, and heart tonics. Cardiac steroids are widely used in the modern treatment of congestive heart failure and for treatment of atrial fibrillation and flutter. Yet their toxicity remains a serious problem.
