Harjot K. Saini-Chohan and Grant M. Hatch Pages 206 - 219 ( 14 )
Congestive heart failure (CHF), a complex clinical syndrome with impaired cardiac pump function, occurs as a consequence of mechanical deformities (pressure and volume overload), myocardial abnormalities (neurohormonal disorders, myocarditis, cardiomyopathies, inflammation and loss of cardiomyocytes) and rhythmic defects (conduction disturbances, fibrillation and tachycardia). Several studies have demonstrated that chronic activation of sympathetic and renin-angiotensin systems, alteration in myocardial substrate utilization, increase in intracellular Ca2+ concentration, development of oxidative stress, release of pro-inflammatory cytokines and increased production of endothelin are responsible for the maladaptive cardiac and subcellular remodeling depending upon the type and stage of heart failure. A variety of pharmacological agents have been used to prevent the development and progression of CHF under different experimental and clinical settings. Although these drugs belong to specific classes, depending on their mechanism of action, individual drug biotransformation into different metabolites makes them distinct chemical moieties. Thorough understanding of biological effects of these pharmacological agents and metabolism is necessary to establish the basis for their preeminent use in clinical settings. The purpose of this review is to present a mechanistic understanding for the biological activities of different drugs used to treat CHF and to provide an insight of different metabolites formed after biotransformation of these chemical entities. Since development of CHF is a multifactorial and heterogeneous process, induction of combination regimens and improvement in patient compliance are the major challenges for future drug development.
Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, aldosterone antagonists, diuretics, digoxin, vasodilators
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A307 Chown Building, 753 McDermot Ave, Winnipeg, Manitoba, Canada R3E OT6.