cardiovascular-agents and pirbuterol

The animal and human pharmacology of several new drugs (prazosin, trimazosin, pirbuterol, and carbazeran) useful in the treatment of congestive heart failure (CHF) is delineated in relation to the pharmacology of other agents employed for CHF management. Prazosin and trimazosin are selective alpha 1-blockers that cause a balanced increase in cardiac output (CO) and reduction in left ventricular filling pressure (LVFP); the reduction in diastolic blood pressure with these drugs is significantly related to increase in treadmill exercise, fall in LVFP, and increase in CO. Pirbuterol is a relatively selective beta 2-agonist with somewhat greater effects on CO than on LVFP. Early promise in CHF therapy is being shown by a novel series of cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitors with combined direct inotropic and vasodilator effects. Double-blind long-term studies demonstrate persistent efficacy of prazosin and trimazosin in CHF as measured by improvement in New York Heart Association functional class, treadmill exercise performance, and noninvasive measures of cardiac function; these data are supported by studies in which repeat cardiac catheterization has been performed after several months of therapy. Double-blind studies of other CHF drugs are in progress.

Topics: Animals; Asthma; Carbamates; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Ethanolamines; Heart Failure; Hemodynamics; Humans; Hypertension; Piperazines; Prazosin; Quinazolines; Vasodilator Agents

The animal and human pharmacology of several new drugs (prazosin, trimazosin, pirbuterol, and carbazeran) useful in the treatment of congestive heart failure (CHF) is delineated in relation to the pharmacology of other agents employed for CHF management. Prazosin and trimazosin are selective alpha 1-blockers that cause a balanced increase in cardiac output (CO) and reduction in left ventricular filling pressure (LVFP); the reduction in diastolic blood pressure with these drugs is significantly related to increase in treadmill exercise, fall in LVFP, and increase in CO. Pirbuterol is a relatively selective beta 2-agonist with somewhat greater effects on CO than on LVFP. Early promise in CHF therapy is being shown by a novel series of cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitors with combined direct inotropic and vasodilator effects. Double-blind long-term studies demonstrate persistent efficacy of prazosin and trimazosin in CHF as measured by improvement in New York Heart Association functional class, treadmill exercise performance, and noninvasive measures of cardiac function; these data are supported by studies in which repeat cardiac catheterization has been performed after several months of therapy. Double-blind studies of other CHF drugs are in progress.

Topics: Animals; Asthma; Carbamates; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Ethanolamines; Heart Failure; Hemodynamics; Humans; Hypertension; Piperazines; Prazosin; Quinazolines; Vasodilator Agents

Modern management of congestive heart failure (CHF) employs inotropic drugs, vasodilators, and diuretics. Although pharmacologic classification of drugs is possible in animals, identification of predominant hemodynamic mechanisms in humans is more complex, because many effects of vasodilators and inotropic drugs are similar. We compared the effects of a vasodilator, prazosin, and two agents with both inotropic and vasodilatory properties, amrinone and pirbuterol, on cardiac index (CI), mean aortic pressure, left ventricular stroke work index (LVSWI), LV filling pressure (LVFP), systemic vascular resistance, LV ejection fraction (LVEF), and myocardial O2 consumption (MVO2) in 34 patients with advanced CHF. We concluded that (1) a rise in CI and LVEF, together with a fall in LVFP, does not necessarily indicate an inotropic effect; (2)both CI and LVEF may be increased by an inotropic mechanism in advanced CHF without a rise in MVO2; and (3) a drug-induced rise in LVSWI with stable or lower LVFP suggests an inotropic mechanism of action.

Topics: Aminopyridines; Amrinone; Cardiotonic Agents; Cardiovascular Agents; Drug Evaluation; Energy Metabolism; Ethanolamines; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Prazosin; Vasodilator Agents