Positive inotropic agents

Treatment focuses on increasing CO with positive inotropic agents and/or replacing intravascular fluids... 

Just as Class III agents can exhibit positive inotropy, some positive inotropic agents demonstrate Class III electrophysiologic activity. The increase in intracellular calcium-ion concentration produced by the inotropic... 

In the United States, two potent orally active positive inotropic agents, CI-914 [imazodan hydrochloride CAS 89198-09-4, (15)] and CI-930 [CAS 86798-59-6, (16)], both characterized by a 4T(l/7-imidazol-l-yl)phenyl substituent attached to C-6 of a 4,5-dihydro-3(2//)-pyridazinone system, have been developed [16]. Patents exist on compounds of this type and related unsaturated pyridazinones [17-21] and also on homologues in which the... 

In the United States, compound RGW-2938 (47) has been developed as a selective positive inotropic agent its synthesis and pharmacological actions have been reviewed [161]. Related compounds, in which the dihydro-pyridazinone system is replaced by a benzoxazinyl system instead of the quinazoline system, have recently been studied in India and in the United States [162,163]. From this series, bemoradan (48) was found to be a very potent orally active, long-acting inotropic vasodilator agent in canine models (i.v. ED5o = 5.4 //g/kg 24h duration of action) [163]. 

H. G. Ramjit, M. M. Singh and A. B. Coddington, Gas chromatographic/mass spectro-metric analysis of methyl methanesulfonate and ethyl methanesulfonate in the bismesy-late salt of DPI 201-106, a positive inotropic agent for the treatment of heart failure. Journal of Mass Spectrometry, 31(8), 867-872.1996. 

Drug therapy and the use of cardioverter defibrillators will not improve the prognosis of patients in this stage. Cardiac transplantation will be the only option. With the patient s informed consent, even inactivation of an ICD can be considered as a possible option in this stage of the disease. The critical issue is fiuid retention control. To achieve this objective, the administration of intravenous positive inotropic agents cannot be weaned off. As a strategy for palliation, vasodilators are sometimes used even though they may worsen mortality. 

A) Intravenous (cAMP elevating) positive inotropic agents... 

Mechanism of Action A positive inotropic agent that inhibits myocardial cyclic adenosine monophosphate (cAMP) phosphodiesterase activity and directly stimulates... 

Packer M. The development of positive inotropic agents for chronic heart failure how have we gone astray J Am Coll Cardiol 1993 22(suppA) 119A-126A. 

Drugs That Increase Myocardial Contraction Force (Positive Inotropic Agents)... 

Agents that increase myocardial contraction force (positive inotropic agents] Digitalis glycosides... 

Hence, phosphodiesterase inhibitors such as inamrinone and milrinone are classified as positive inotropic agents because they increase myocardial con-... 

Feldman, A. M. 1993. Classification of positive inotropic agents. J. Am. Coll. Cardiol. 22 1223-1227. 

Strategies include improving myocardial contractility (e.g., positive inotropic agents), lower sodium retention (diuretics, ACE inhibitors), and decreasing arteriolar and venous resistance in order to decrease work load (vasodilators and ACE inhibitors) and to increase exercise tolerance. 

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). 

Positive inotropic agents enhance cardiac muscle contractility, and thus increase cardiac output. Although these drugs act by different mechanisms, in each case the inotropic action is the result of an increased cytoplasmic calcium concentration that enhances the contractility of cardiac muscle. 

Dobutamine is a relatively selective betai-adrenoceptor agonist with only slight beta2- and alpha-adrenoceptor activity. It has been developed as a positive inotropic agent that is less vasoconstrictive than high doses of dopamine. 

Coined WS, Wright RF, Braunwald E. New positive inotropic agents in the treatment of congestive heart failure. Mechanisms of action and recent clinical developments. N Engl J Med 1986 314(5) 290-9 1986 314(6) 349-58. 

Renard M, Jacobs P, Melot C, Dresse A, Bernard R. Le sulmazol un nouvel agent inotrope positif. [Sulmazole a new positive inotropic agent.] Ann Cardiol Angeiol 1984 33(4) 219-22. 

MOA Digoxin (cardiac glycoside) is a positive inotropic agent that inhibits the Na+/K+ ATPase pump. Inhibition of the pump causes an increase in intracellular sodium that allows the Na+/Ca exchanger to increase intracellular calcium. The heart is then able to use the increased intracellular calcium to increase contractility. 

Pimobendan is a new positive inotropic agent that is said to be a calcium-sensitizing agent, which increases the force of contraction at a given prevailing calcium ion concentration. It has been evaluated in dogs but not yet in horses. 

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