Inotropes

 

Inotropes – Study Notes

Definition

• Inotropes = class of medications that increase cardiac contractility, which in turn improves cardiac output (CO).

• Recall:

  • CO = HR × Stroke Volume (SV)

  • SV = preload + afterload + contractility

• By increasing contractility → SV ↑ → CO ↑.

• Used primarily in low cardiac output states, especially heart failure.

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Mechanisms of Action

1. Adrenergic receptor stimulation (sympathetic system):

   • Beta-1 (heart): ↑ HR and ↑ contractility.

   • Beta-2 (lungs/vasculature): vasodilation.

   • Alpha: vasoconstriction (dose dependent).

2. Phosphodiesterase (PDE) inhibition:

   • PDE normally breaks down cAMP.

   • Inhibition → ↑ cAMP → ↑ intracellular Ca²⁺ → stronger cardiac contraction.

   • Also prevents cGMP breakdown in vessels → vasodilation.

Categories & Drugs

1. Catecholamines

• Act on adrenergic receptors.

• Some used primarily as vasopressors but have inotropic effects.

a. Epinephrine

• Non-selective adrenergic agonist.

• Low dose → more Beta-1 effect.

• ↑ HR, ↑ contractility, vasoconstriction.

• Dose: 1–10 mcg/min (1 mg in 250 mL).

• Onset: 1–2 min; titrate q5–10 min.

• Central line only.

b. Dopamine

• Dose dependent receptor activity:

  • Low dose: beta effects (↑ HR, ↑ contractility).

  • High dose: alpha effects (vasoconstriction).

• Dose: 2–20 mcg/kg/min (5–10 mcg/kg/min for inotropic effect).

• Onset: ~5 min; titrate q10 min.

• Can be given peripherally, but central preferred.

c. Dobutamine (Dobutrex)

• Primarily Beta-1 agonist → strong inotrope.

• Also Beta-2 agonist → vasodilation → possible hypotension.

• Minimal alpha effect.

• Dose: 2.5–20 mcg/kg/min.

• Onset: 1–10 min; adjust q5–10 min (usually titrate down, not to protocol).

• Central line preferred.

d. Isoproterenol (Isuprel)

• Potent Beta-1 and Beta-2 agonist.

• Strong chronotrope (↑ HR) → used for bradycardia.

• Also has inotropic effects.

• No alpha activity.

• Vasodilation risk → hypotension.

• Dose: 2–20 mcg/min (1–4 mg in 250 mL).

• Onset: 1–2 min; titrate q3–5 min.

• Peripheral or central administration.

• Rarely used today.

2. Phosphodiesterase (PDE-3) Inhibitors

a. Milrinone (Primacor)

• Inhibits PDE-3 → ↑ cAMP in cardiac cells → ↑ Ca²⁺ → ↑ contractility.

• Also ↑ cGMP in vascular smooth muscle → vasodilation (arterial + venous).

• Greater vasodilatory effect than beta-2 agonists.

• Concentration: 1 mg/10 mL (often in 5 mg/50 mL, 20 mg/100 mL, or 40 mg/200 mL).

• Dose: 0.25–1 mcg/kg/min (common range 0.375–0.75 mcg/kg/min).

• Onset: 5–15 min; long half-life.

• Titrate q15–30 min (usually titrate down when weaning).

• Can be given peripherally or centrally.

b. Amrinone – rarely used, less relevant.

Key Clinical Notes

• Catecholamines: mainly adrenergic; rapid titration; risk of tachyarrhythmias, hypertension, or hypotension (via beta-2).

• PDE inhibitors: slower onset, longer half-life; stronger vasodilatory effects → monitor for hypotension.

• Central line preferred for most due to risk of extravasation.

• Used in acute decompensated heart failure, shock states, or perioperative cardiac support.

Summary

• Inotropes = drugs that increase contractility and cardiac output.

• Two main mechanisms:

  1. Adrenergic receptor stimulation (catecholamines).

  2. PDE-3 inhibition (milrinone).

• Catecholamines = fast acting, dose dependent receptor activity.

• Milrinone = unique, longer acting, strong vasodilatory effect.

• Always monitor blood pressure, HR, arrhythmias, and perfusion when using inotropes.

Would you like me to also create a drug comparison table (Epi, Dopamine, Dobutamine, Isoproterenol, Milrinone) with receptor targets, dose ranges, onset, and key notes for quick study?