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INTRODUCTION

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Inotropes are agents that affect cardiac contractility. Positive inotropes, or inotropes that increase contractility, augment cardiac output, thereby enhancing end-organ perfusion. The pharmacology of inotropes varies not only with drug class, but also with drug dosage. Inotropic therapy routinely treats a wide variety of cardiovascular disease processes, including cardiogenic shock complicating acute myocardial infarction, acute decompensated heart failure, cardiopulmonary arrest, right ventricular infarction, and bradyarrhythmias. In perioperative medicine, inotropes frequently support patients with low cardiac output syndrome while weaning from cardiopulmonary bypass and during recovery.

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CATECHOLAMINES

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Several frequently used inotropic agents are sympathomimetics, drugs which mimic the effects of endogenous catecholamines (Table 164-1). The primary adrenergic receptors utilized by these agents are alpha-1, beta-1, beta-2, and the dopaminergic receptors, D1 and D2.

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Table Graphic Jump Location
TABLE 164-1   Summary of Catecholaminergic Inotropes and Their Receptor Selectivities 
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Activation of beta-1 receptors, found exclusively in cardiac muscle, is chiefly responsible for the inotropic effect of sympathomimetics. The beta-1 receptor mediates the intracellular formation of cyclic adenosine monophosphate (cAMP); with increased activation, cAMP is increased, producing a greater release of Ca2+ from the sarcoplasmic reticulum. Ca2+ facilitates the binding of troponin C to the actin–myosin complex, producing forceful muscular contraction.

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In addition to increased inotropy, activation of the beta-1 receptor results in increased chronotropy (heart rate), increasing myocardial oxygen demand, which may be associated with new or worsening ischemia. Beta agonists also increase cardiac arrhythmia risk, attributable either to increased conductance through the sinoatrial node or ectopy. These effects are dose-limiting, meaning that at some drug level, serious side effects prevent further escalation of dosing.

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Though an agent’s activation of other receptor subtypes does not directly contribute to inotropic action, the relative drug-receptor selectivity plays an important role in drug selection. The alpha-1 receptor is found primarily on vascular smooth muscle cells, and its activation results in vasoconstriction, increasing systemic vascular resistance. The beta-2 receptor functions as the counterbalance to alpha-1, decreasing intracellular Ca2+ bioavailability, and encouraging vasodilation. Lastly, the dopaminergic receptors, found in the renal and splanchnic vasculature, produce renal and mesenteric vasodilation.

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Epinephrine

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Epinephrine, an analog to the adrenaline produced by the adrenal medulla, interacts with alpha-1, beta-1, and beta-2 receptors. Its interaction with receptors is dose-dependent. At lower doses (<0.04 mcg/kg/min), the beta-adrenergic effects dominate, resulting in positive inotropy and vasodilation. Moderate doses (0.04-0.12 μg/kg/min) produce mixed alpha and beta effects, with alpha-mediated vasoconstriction overshadowing beta-induced vasodilation. Finally, high doses of epinephrine (>0.12 μg/kg/min) produces potent vasoconstriction and negligible beta-mediated effects.

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Norepinephrine

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Endogenous norepinephrine is a neurotransmitter released ...

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