Captopril in the treatment of congestive heart failure.

This 3-part discussion of captopril, the first oral angiotensin converting enzyme (ACE) inhibitor, focuses on the clinical use and superiority of this agent to standard treatments and the new observations that use can improve the overall poor survival associated with heart failure. Today, as in the past, treatment of CHF includes digoxin and diuretics. Vasodilators have been relegated by some to the role of supplementing therapeutic regimens when patients remain symptomatic. Recently, controlled studies have shown that the introduction and supplementation of therapeutic regimens with ACE inhibitions and specifically captopril is associated with substantial clinical benefits: Symptoms are reduced as hemodynamics and exercise capacity improve, metabolic derangements (including fluid retention, potassium and magnesium loss and sympathetic nervous activation) are reduced with resultant favourable effects on arrhythmia frequency and finally the newest and most dramatic observation of improved survival. This review will briefly summarize these developments and assist in the clinically important aspects of this therapy for practicing physicians. Guidelines for the clinical use of captopril: In patients with confirmed dilated cardiomyopathy, captopril improves stroke volume in response to afterload reduction, but in volume-contracted patients vasodilation may be associated with hypotension. Therefore, prior to initiating captopril, the diuretic dosage should be reduced, particularly in low serum sodium concentration states if intravascular volume is depleted. Potassium supplements should be stopped due to the expected decrease of aldosterone production and improved potassium retention. Initial therapy should be started with a low captopril dosage (2 to 3 times 6.25 mg/day), maintenance dosages are 25 or 50 mg b.i.d. or t.i.d. Superiority to other vasodilator drugs and use in mild cases: In studies of acute and chronic CHF, captopril improves hemodynamics, exercise tolerance, and reduces symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of the effects of disopyramide phosphate on left ventricular function and the peripheral circulation.

In the absence of preexistent myocardial dysfunction, the risk of producing cardiac decompensation in patients being treated with any of the conventional antiarrhythmic agents is low. The availability of disopyramide for clinical use in 1977 produced optimism for an effective antiarrhythmic agent that was free of the well-known immediate and late toxicities of quinidine and procainamide. Unfortunately, shortly after its clinical introduction, reports appeared that raised concern about the negative inotropic actions of disopyramide and the possible role of this drug in precipitating heart failure. In clinical use, the frequency of adverse effects on ventricular function appeared to be out of proportion to disopyramide's greater negative inotropic activity and the contrasting (augmenting) effect on the peripheral vascular resistance compared to that of either quinidine or procainamide, suggesting that the other factors contributed to these observations. Review of the reported literature reveals that certain factors encourage such adverse reactions. These primarily include the routine use of oral and especially intravenous loading dosages of disopyramide in an effort to attain rapid onset of action, the failure to adequately reduce dosages of disopyramide in the setting of compromised renal function, and, most importantly, the use of standard (and even loading) dosages in patients with active heart failure, compromised left ventricular function, or a history of heart failure. The avoidance of loading dosages of disopyramide, adequate reductions of maintenance dosages in the setting of renal insufficiency, gradual dose titration for additional drug action, and omission of patients with decompensated heart failure or significant left ventricular dysfunction should significantly enhance safety in the use of disopyramide.

A new oral slow release form of isosorbide dinitrate. Effect on the hemodynamics and exercise capacity of patients with angina.

To assess the bioavailability of a new oral and slow release form of isosorbide dinitrate (ISDN-SR), we evaluated 12 patients with confirmed coronary artery disease, chronic stable angina pectoris and abnormal maximal exercise tests (angina-limited and associated with greater than or equal to 0.1 mV ST displacement). Each patient was known to have an increased exercise time after 0.4 mg of sublingual nitroglycerin. Patient responses to exercise on the treadmill at two, four, six, and eight hours after the double-blind administration of 40 mg of ISDN-SR were compared to an identical placebo. It is concluded that 40 mg of this slow release form of isosorbide dinitrate is bioavailable for at least eight hours as demonstrated by significantly improved exercise capacity of the majority (64 percent) of angina patients in this study, each of whom demonstrated anginal limitation to exercise and favorable responses to 0.4 mg of sublingual nitroglycerin.