Inotropes short-acting

Class II drugs are classical (3-adrenoceptor antagonists such as propranolol, atenolol, metoprolol or the short-acting substance esmolol. These drugs reduce sinus rate, exert negative inotropic effects and slow atrioventricular conduction. Automaticity, membrane responsiveness and effective refractory period of Purkinje fibres are also reduced. The typical extracardiac side effects are due to (3-adrenoceptor blockade in other organs and include bronchospasm, hypoglycemia, increase in peripheral vascular resistance, depressions, nausea and impotence. 

None of the available oral phosphodiesterase inhibitors has become established in routine therapy, because the short-term benefit of the increased contractility has been offset by an increased mortality (presumably due to arrhythmias) on chronic dosing. A similar fate befell flosequinan, a positive inotrope which acted through the phosphatidylinositol system. Their use is restricted to short-term symptom control prior to, for example, transplanation. 

Current data suggest little benefit on clinical outcomes beyond symptom relief for dihydropyridine calcium channel blockers in the setting of ACS. Moreover, the use of first-generation short-acting dihydropyridines, such as nifedipine, should be avoided because they appear to worsen outcomes through their negative inotropic effects, induction of reflex sympathetic activation, tachycardia, and increased myocardial ischemia. ... 

Some PHOSPHODIESTERASE INHIBITORS (e.g. cnoximone and milrinone) are valuable, and some exert most of their effect on the myocardium (those acting at a heart-specific subtype of this enzyme (type III phosphodiesterase) to raise the intracellular concentration of cAMP) and may be used as positive INOTROPIC AGENTS in the short-term treatment of severe congestive heart failure. 

Inhibitors of a heart-specific subtype (type III) phosphodiesterase, which are positive inotropics, may be used in the short-term treatment of severe congestive cardiac failure, e.g. amrinone, enoximone and milrinone. However, developments of oral formulations of drugs of this type have been halted by the results of the PROMISE trial (Prospective Randomised Milrinone Survival Evaluation trial) which documented a paradoxical increase in mortality in class IV heart failure patients randomised to receive milrinone. However, some benzimidazole derivatives with class III phosphodiesterase inhibitor actions seem to be beneficial in heart failure. The agent vesnarinone is an orally active compound that may act as a class III phosphodiesterase inhibitor but appears to be a vasodilator with multiple mechanisms. See HEART FAUURE TREATMENT INOTROPIC AGENTS. 

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