Drugs that Regulate Cardiac Contractility

Cardiac muscles contract when action potentials depolarize plasma membranes. Decreased cardiac contractility is associated with dysregulation of calcium homeostasis, changes in cAMP-dependent regulation of contractile proteins, and alterations in β-adrenoceptor activity.⁸ The most common causes of contractile dysfunction include coronary artery disease resulting in myocardial infarction, systemic hypertension, and valvular disease. Progressive contractile dysfunction leads to heart failure (HF).⁸

The central role of intracellular Ca²⁺ and cAMP in cardiac muscle contraction provides a basis for the classification of agents with positive inotropic effects as (1) cardiac glycosides, (2) β1-adrenoceptor agonists, and (3) phosphodiesterase inhibitors.⁸ Currently, the cardiac glycoside digoxin, is the only drug in the top 300 that regulates cardiac contractility (Table 4).^2,8,10 It inhibits Na⁺/K⁺-ATPase and thereby increases intracellular Ca²⁺ concentration in myocytes and exerts a positive inotropic effect.⁸