Inotropes and More

Inotropes are drugs that change the force (contractility) of cardiac muscle contraction.

• Positive inotropes → increase contractility.
• Negative inotropes → decrease contractility.

Positive Inotropes (used in shock, heart failure, cardiogenic collapse)

1. Catecholamines (β-adrenergic stimulation → ↑ cAMP, ↑ Ca²⁺ influx)

   • Dobutamine: β₁ agonist → ↑ contractility, some vasodilation (good for cardiogenic shock, HF).
   • Dopamine: dose-dependent (low = renal vasodilation, medium = β₁ ↑ contractility, high = α ↑ vasoconstriction).
   • Epinephrine: β₁/β₂/α agonist → powerful inotrope and vasoconstrictor (cardiac arrest, anaphylaxis).
   • Norepinephrine: α > β₁ (mainly vasoconstriction, mild inotropy).

2. Phosphodiesterase-3 Inhibitors (PDE3i)

   • Milrinone, Inamrinone → prevent cAMP breakdown → ↑ Ca²⁺ influx, vasodilation (inodilators).
   • Used in acute decompensated HF, pulmonary hypertension.

3. Cardiac Glycosides

   • Digoxin: inhibits Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → ↑ Ca²⁺ via Na⁺/Ca²⁺ exchanger.
   • Slows AV node conduction (helpful in AFib) but risk of toxicity (arrhythmias, vision changes).

4. Calcium Sensitizers

   • Levosimendan (not widely available in U.S.): ↑ troponin C sensitivity to Ca²⁺ + PDE inhibition → inotropy + vasodilation.

Negative Inotropes (reduce cardiac workload, contractility)

• Beta-blockers (e.g., metoprolol, propranolol, carvedilol).
• Calcium channel blockers (non-dihydropyridines: verapamil, diltiazem).
• Antiarrhythmics (Class I agents like flecainide).

Key Clinical Uses

• Positive inotropes → acute HF, cardiogenic shock, post-cardiac surgery, some arrhythmias.
• Negative inotropes → ischemic heart disease, chronic HF (beta-blockers), arrhythmias, hypertension.

Core Definitions

1. Inotropy → force of contraction

   • Positive inotrope → ↑ contractility
   • Negative inotrope → ↓ contractility

2. Chronotropy → heart rate (via SA node)

   • Positive chronotrope → ↑ HR
   • Negative chronotrope → ↓ HR

3. Dromotropy → conduction velocity (mainly AV node)

   • Positive dromotrope → faster conduction
   • Negative dromotrope → slower conduction

4. Bathmotropy (or basmotropy) → excitability / threshold of cardiac muscle fibers

   • Positive bathmotrope → ↑ excitability (cells fire more easily)
   • Negative bathmotrope → ↓ excitability

Agents Affecting Each Property

1. Inotropes (Contractility)

• Positive inotropes:
  • Catecholamines: Dobutamine, Dopamine (β1), Epinephrine, Norepinephrine
  • PDE-3 inhibitors: Milrinone, Inamrinone
  • Cardiac glycosides: Digoxin
  • Calcium sensitizers: Levosimendan
• Negative inotropes:
  • Beta-blockers (Metoprolol, Propranolol, Carvedilol)
  • Non-DHP calcium channel blockers (Verapamil, Diltiazem)
  • Class I antiarrhythmics (e.g., Flecainide, Quinidine)

2. Chronotropes (Heart Rate)

• Positive chronotropes:
  • Atropine (antimuscarinic)
  • Isoproterenol (β agonist)
  • Epinephrine, Dopamine (β1 action)
  • Theophylline (adenosine antagonist, PDE inhibitor)
• Negative chronotropes:
  • Beta-blockers (↓ SA node firing)
  • Digoxin (via ↑ vagal tone)
  • Non-DHP CCBs (Verapamil, Diltiazem)
  • Ivabradine (If channel blocker)

3. Dromotropes (Conduction Velocity, esp. AV node)

• Positive dromotropes:
  • Atropine (blocks vagal inhibition)
  • Catecholamines (β1 agonists) → ↑ AV conduction
• Negative dromotropes:
  • Beta-blockers
  • Non-DHP CCBs (Verapamil, Diltiazem)
  • Digoxin (↑ vagal tone)
  • Amiodarone (antiarrhythmic, slows conduction)

4. Bathmotropes (Excitability)

• Positive bathmotropes (↑ excitability = pro-arrhythmic):
  • Digitalis (at toxic levels)
  • Catecholamines (↑ automaticity)
  • Hypercalcemia, Hyperkalemia (mild ↑)
• Negative bathmotropes (↓ excitability, stabilizers):
  • Antiarrhythmics (Class I Na⁺ blockers, Class III K⁺ blockers)
  • Hypocalcemia, Hypokalemia (↓ excitability)
  • Magnesium (used in torsades de pointes to reduce excitability)

Quick Memory Aid:

• Ino = force
• Chrono = time/HR
• Dromo = conduction
• Bathmo = excitability