Inotropic drugs specific agents

Systemic effects are the most important adverse effects of / -blockers. Drug absorbed systematically may produce decreased heart rate, reduced blood pressure, negative inotropic effects, conduction defects, bronchospasm, central nervous system effects, and alteration of serum lipids, and may block the symptoms of hypoglycemia. The -specific agents betaxolol and possibly carteolol (due to ISA) are less likely to produce the systemic adverse effects caused by / -adrenergic blockade, such as the cardiac effects and bronchospasm, but a real risk still exists. The use of timolol as a gel-forming liquid or betaxolol as a suspension allows for administration of less drug per day, and therefore reduces the chance for systemic adverse effects compared with the aqueous solutions. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

Examples of specific drugs used in the treatment of chronic heart failure include digitalis glycosides (e.g., digoxin, positive inotropic agent), diuretics (hydrochlortiazide and furosemide), and vasodilators (nitrates such as nitroglycerin, ACE inhibitors, such as captopril, and hydralazine). 

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. 

Dopamine and dobutamine are the positive inotropic agents most often used for the shortterm support of the circulation in advanced heart failure. These drugs act via stimulation of the cardiac myocyte dopamine Dj and adrenergic receptors, leading to stimulation of the G -adenylyl cyclase-cyclic AMP-PKA pathway. Isoproterenol, epinephrine, and norepinephrine, although useful in specific circumstances, have little role in the treatment of heart failure see Chapter 10). 

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