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The effects of amrinone vary widely with species and experimental condition; therefore, its inotropic effects are variable. [3] A loss in sensitivity to phosphodiesterase 3 inhibitors, including amrinone, has been observed in end stage heart failure in humans; other treatment options may be more useful for improvement in these stages. [3]
Cardiotonic agents are typically employed as short-term and non-routine therapies for heart failure patients. [71] They are specifically reserved for those with contractile dysfunction in the left ventricles (lower chambers of the heart), low cardiac output, and low blood pressure, placing them at risk of inadequate organ perfusion. [72]
PDE3 inhibitors are indicated as inotropics for the therapy of acute heart failure if catecholamines are ineffective. [2] Well controlled studies have shown that these drugs generally increase mortality , [ 3 ] when used for the therapy of acute heart failure, so they have to be applied under close observation.
PKA also phosphorylates components on myofilaments allowing actin and myosin to interact more easily and thus increasing contractility and the inotropic state of the heart. Milrinone allows stimulation of cardiac function independently of β-adrenergic receptors which appear to be down-regulated in those with heart failure. [13]
Vesnarinone is a cardiotonic agent. [1] A mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. Vesnarinone improves ventricular performance most in patients with the worst degree of heart failure.
Levosimendan is a calcium sensitizer — it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its positive inotropic effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium
Negative inotropic agents decrease myocardial contractility and are used to decrease cardiac workload in conditions such as angina. While negative inotropism may precipitate or exacerbate heart failure in the short term, certain beta blockers (e.g. carvedilol , bisoprolol and metoprolol ) have been believed to reduce long-term morbidity and ...
Istaroxime is a positive inotropic agent [2] that mediates its action through inhibition of sodium/potassium adenosine triphosphatase (Na+/K+ ATPase). [7] Na+/K+ ATPase inhibition increases intracellular sodium levels, which reverses the driving force of the sodium/calcium exchanger, inhibiting calcium extrusion and possibly facilitating calcium entry., [5] [8]
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