cardiovascular-agents and sulmazole

This selective review of a few of the advances made in recent years indicates that we are entering a new era in cardiovascular pharmacology. Drugs with novel mechanisms of action, and modifications of existing drugs, are being developed in constantly increasing numbers. The clinical evaluation of these drugs will be an exciting but difficult challenge.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Aminopyridines; Amrinone; Animals; Calcium Channel Blockers; Cardiovascular Agents; Dopamine; Heart Rate; Humans; Imidazoles; Milrinone; Myocardial Contraction; Pyridones; Receptors, Histamine; Vasodilator Agents

Compounds with phosphodiesterase inhibitory activity stimulate myocardial contractility by increasing the intracellular cyclic AMP concentrations. They can also increase Ca2+ entry and inhibit Ca2+ sequestration by the sarcoplasmic reticulum. Xanthines produce bronchodilation with associated venous and arteriolar dilation. However, their use is limited by their positive chronotropic effect and other side effects at high plasma levels. New phosphodiesterase inhibitors have been perfected: they are more specific with little chronotropic effect. Increasing the sensitivity of the myofilaments to Ca2+, and other unclear mechanisms may be involved in the inotropic action of these drugs. These new promising active compounds are described and discussed. They augment cardiac performance and improve regional distribution of blood flow and symptoms. However, their influence on the long-term outcome of severe heart failure has yet to be determined.

Topics: Aminopyridines; Amrinone; Calcium; Carbamates; Cardiotonic Agents; Cardiovascular Agents; Enoximone; Heart Failure; Hemodynamics; Humans; Imidazoles; Milrinone; Myocardial Contraction; Phosphodiesterase Inhibitors; Pyridones; Quinazolines; Stimulation, Chemical; Time Factors; Xanthines

1. Non-invasive measurements of blood pressure (BP) are method-specific estimates of actual blood pressure. The agreement of the auscultatory Korokoff V ('disappearance' of sound, kv) and Korokoff IV ('sound muffling' kiv) cut-off points in measuring diastolic blood pressure (DBP) was evaluated in healthy subjects in the presence of various controlled inodilatory interventions. 2. Eating (n = 8), 10 min i.v. infusion of 1 microgram min-1 isoprenaline and adrenaline (n = 12), p.o. administration of 40 mg of the PDE-III inhibitors isomazole and meribendan (n = 18) and p.o. administration of 1200 mg celiprolol (n = 15) caused evident chrono-inodilatory responses: average HR increases of 7, 19, 10, 17, 17 and 8 beats min-1, estimated CO increases of 1.6, 4.5, 2.3, 1.9, 2.6 and 1.8 1 min-1 and average shortening of QS2c of 18, 41, 8, 37, 42 and 9 ms for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively. 3. In general, there was good agreement between DBPkV and DBPkIV measurements before the administration of the inodilatory treatments (bias DBPkV-DBPkIV: 1-2 mm Hg) but the extent of inodilatory DBP reduction (-8, -6, -10, -2, -7 and -8 mm Hg according to DBPkIV for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively) was substantially overestimated when based on Korotkoff-V rather than -IV (bias DBPkV-DBPkIV in estimating the inodilatory effect on DBP: -8, -12, 1, -13, -12 and -7 mm Hg for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Blood Pressure; Blood Pressure Determination; Cardiotonic Agents; Cardiovascular Agents; Celiprolol; Cross-Over Studies; Eating; Epinephrine; Heart Rate; Humans; Imidazoles; Infusions, Intravenous; Isoproterenol; Male; Phosphodiesterase Inhibitors; Pyridazines; Reproducibility of Results; Vasodilator Agents