quazinone and piroximone

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Administration, Oral; Aminopyridines; Amrinone; Cardiotonic Agents; Coenzymes; Enoximone; Heart; Heart Failure; Hemodynamics; Humans; Imidazoles; Injections, Intravenous; Milrinone; Nifedipine; Oxyfedrine; Phosphodiesterase Inhibitors; Pyridazines; Pyridones; Quinazolines; Ubiquinone

Survival in severe left ventricular failure is poor but has not been widely assessed since the introduction of several new nonglycosidic, nonsympathomimetic oral inotropic agents for long-term therapy. We examined retrospectively the survival of 82 patients with severe left heart failure during long-term treatment with oral milrinone (17 patients), posicor (12 patients), enoximone (47 patients), and piroximone (6 patients). Sixty-five patients were in New York Heart Association (NYHA) functional class 4, 15 patients were in class 3, and two patients were in class 2. There were 57 patients with ischemic and 25 patients were in class 2. There were 57 patients with ischemic and 25 patients with nonischemic etiology of left heart failure. Most patients were referred for inotropic therapy after failing to respond to conventional agents, including vasodilators. However, in almost all patients, marked hemodynamic and clinical improvement occurred initially. Overall survival was 36 percent at six months, the majority of deaths occurring during the first three months. Survival in relation to etiology of heart failure showed a trend toward increased mortality in patients associated with ischemic heart disease vs non-ischemic dilated cardiomyopathy. Sudden death mortality was also higher in the ischemic group (28 percent at six months vs 5 percent at six months; p less than 0.05). There was a trend toward reduced sudden death mortality in patients on antiarrhythmic agents during inotropic therapy (p = 0.06). We conclude that overall survival in symptomatic patients with severe left ventricular failure remains very low during long-term therapy with several new oral inotropic agents. Sudden death appears higher in patients with an ischemic etiology during therapy with these agents.

Topics: Administration, Oral; Aged; Anti-Arrhythmia Agents; Cardiotonic Agents; Death, Sudden; Drug Evaluation; Enoximone; Female; Heart Failure; Humans; Imidazoles; Male; Middle Aged; Milrinone; Pyridones; Quinazolines; Retrospective Studies; Time Factors

The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use result, in the first place, from an insufficient understanding of their mechanism of action. Some of them (pirbuterol, salbutamol, terbutaline, penoterol) seem to act preferentially on B2 adrenergic receptors and the haemodynamic effect results, in part or predominantly, from the vasodilator action which they cause. On the other hand, other agents (prenalterol, ICI 108-87) show a relative selectivity for B1 adrenergic receptors. Ibopamine exerts its action on B1 receptors and dopaminergic receptors. A second problem concerns the hypothetical character of their long term therapeutic activity. A major problem in the use of several of these sympathomimetic agents in chronic treatment is the appearance of a desensitization of the beta receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminopyridines; Amrinone; Cardiotonic Agents; Colforsin; Deoxyepinephrine; Humans; Imidazoles; Levodopa; Milrinone; Practolol; Prenalterol; Propanolamines; Pyridones; Quinazolines; Xamoterol