Drug-patient interactions and their relevance in the treatment of heart failure.
The effects of congestive heart failure (CHF) on drug disposition and elimination are many and varied. Indeed, the pharmacokinetics of many of the drugs used to treat CHF are significantly altered by the patient's underlying condition. Reduced gastric emptying in CHF delays absorption and decreases the peak plasma concentrations of furosemide, bumetanide, and digoxin. Moreover, drugs that have a high hepatic extraction ratio (organic nitrates, morphine, prazosin, and hydralazine) achieve higher than expected plasma concentrations in patients with CHF. In contrast, drugs requiring biotransformation to active forms, e.g., angiotensin-converting enzyme (ACE) inhibitors such as enalapril, perindopril, quinapril, and ramipril, generally have lower than expected plasma concentrations. Nevertheless, ACE inhibitors can impair renal function in CHF, leading to an actual increase in plasma concentrations. However, decreases in absorption and first-pass metabolism are often offset by reduced hepatic and renal clearance. The overall absorption of lisinopril may be reduced in some CHF patients; consequently, the onset of effect is delayed but is often more prolonged.