Miscellaneous drugs of the cardiovascular system**
Dopamine: It is the precursor to norepinephrine. At low doses (0.5 to 3 microgram/kg/min), it stimulates D1 and D2 receptors, causing vasodilation and increasing circulation in the renal, coronary, mesenteric and cerebral vasculature. It promotes natriuresis. At intermediate doses (3 to 10 microgram/kg/min), dopamine binds to and activates beta 1 receptors, resulting in positive inotropy, chronotropy and mild increase in systemic vascular resistance. At doses higher than 10 microgram/kg/min, vasoconstriction by alpha 1 stimulation is predominant. It is used in the treatment of shock, symptomatic bradycardia and heart failure.
Dobutamine: It activates chiefly beta 1 and beta 2 receptors. Effects include positive inotropy and chronotropy. Vasoconstriction occurs only at high doses > 20 microgram/kg/min. It is used in the treatment of decompensated heart failure, cardiogenic shock, and symptomatic bradycardia. It is diagnostically used in dobutamine stress echo or imaging as it increases myocardial oxygen consumption.
Norepinephrine: It is a potent alpha 1 receptor agonist with modest beta agonist activity, which renders it a powerful vasoconstrictor with less potent direct inotropic properties. Norepinephrine primarily increases systolic, diastolic, and pulse pressure and has a minimal net impact on cardiac output. It only has mild positive chronotropic effect. Prolonged infusion can cause myocyte apoptosis. It is used in the treatment of shock.
Epinephrine: It is a potent activator of alpha 1, beta 1 and beta 2 receptors. High doses may cause myocardial necrosis and apoptosis. It is used in the treatment of shock, cardiac arrest, anaphylaxis and symptomatic bradycardia. Adverse effects include ventricular arrhythmias, sudden cardiac death, ICH and severe hypertension.
Isoproterenol: It is a potent non-selective beta agonist. It increases chronotropy, inotropy with systemic and pulmonary vasodilation. It is used in the treatment of bradyarrhythmias, torsade des pointes and Brugada syndrome.
Phenylephrine: It is a potent activator of alpha 1 receptors causing intense vasoconstriction, elevated blood pressure and reflex bradycardia. It is used in the treatment of severe hypotension especially in the setting of aortic stenosis and HOCM.
Amrinone/Milrinone: They are inhibitors of the enzyme phosphodiesterase. As a result, they increase intracellular cAMP levels and increase myocardial contractility (positive inotropy). They decrease preload, afterload and improve diastolic relaxation (positive lusitropic effect). They are used in the treatment of low cardiac output states like decompensated heart failure. Milrinone is more commonly used as amrinone is associated with thrombocytopenia and hepatotoxicity.
Levosimendan: It is a new inotropic drug. Mechanism of action includes calcium sensitization of contractile proteins like troponin-C, hence improving contractility and opening of ATP dependent K+ channels causing vasodilation. It is used in the treatment of acute and chronic heart failure.
