Miscellaneous drugs of the cardiovascular system

Dopamine: Dopamine 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 a mild increase in systemic vascular resistance.
• At doses higher than 10 microgram/kg/min, vasoconstriction from alpha 1 stimulation is predominant.

It is used in the treatment of shock, symptomatic bradycardia, and heart failure.

Dobutamine: Dobutamine 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 also used diagnostically in dobutamine stress echo or imaging because it increases myocardial oxygen consumption.

Norepinephrine: Norepinephrine is a potent alpha 1 receptor agonist with modest beta agonist activity. This makes it a powerful vasoconstrictor with less potent direct inotropic properties.

• It primarily increases systolic, diastolic, and pulse pressure.
• It has a minimal net impact on cardiac output.
• It has only a mild positive chronotropic effect.
• Prolonged infusion can cause myocyte apoptosis.

It is used in the treatment of shock.

Epinephrine: Epinephrine 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: Isoproterenol is a potent non-selective beta agonist.

• It increases chronotropy and inotropy.
• It causes systemic and pulmonary vasodilation.

It is used in the treatment of bradyarrhythmias, torsade des pointes, and Brugada syndrome.

Phenylephrine: Phenylephrine is a potent activator of alpha 1 receptors.

• It causes 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: Amrinone and milrinone inhibit the enzyme phosphodiesterase.

• This increases intracellular cAMP levels and increases myocardial contractility (positive inotropy).
• They decrease preload and afterload.
• They improve diastolic relaxation (positive lusitropic effect).

They are used in the treatment of low cardiac output states such as decompensated heart failure. Milrinone is more commonly used because amrinone is associated with thrombocytopenia and hepatotoxicity.

Levosimendan: Levosimendan is a newer inotropic drug.

• Its mechanism includes calcium sensitization of contractile proteins such as troponin-C, which improves contractility.
• It also opens ATP dependent K+ channels, causing vasodilation.

It is used in the treatment of acute and chronic heart failure.