Pharmacology 23: Inotropic Agents
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Questions and Answers

What are the tradeoffs to the effect of inotropic agents?

Increased myocardial O2 consumption and potentiation of arrhythmias.

By what mechanism do most inotropic agents increase cardiac contractility?

Increasing cytosolic Ca2+ levels.

What are the four general classes of inotropes?

Cardiac glycosides, B-adrenergic agonists, Phosphodiesterase inhibitors, Calcium sensitizing agents.

What two actions do cardiac glycosides have?

<p>Na/K ATPase inhibition and parasympathetic stimulation.</p> Signup and view all the answers

How do cardiac glycosides increase intracellular Ca2+ levels?

<p>By inhibiting Na/K ATPase pump, which leads to an exchange of Na out for Ca in by Na/Ca exchanger.</p> Signup and view all the answers

What is the result of cardiac glycosides stimulating parasympathetic tone?

<p>Sinus slowing and AV nodal inhibition.</p> Signup and view all the answers

Name three physiological effects of Cardiac Glycosides.

<p>Positive inotropy, negative chronotropy, natriuresis, vasomodulation, and baroreceptor modulation.</p> Signup and view all the answers

In what situations do you use cardiac glycosides?

<p>Systolic myocardial (pump) failure and atrial fibrillation.</p> Signup and view all the answers

Which formulation of Digoxin is most clinically useful?

<p>Elixir.</p> Signup and view all the answers

How is Digoxin metabolized?

<p>Little hepatic metabolism; mostly eliminated unchanged by the kidney.</p> Signup and view all the answers

How do electrolyte disturbances affect the necessary Digoxin dose?

<p>Hypokalemia increases the number of binding sites for Digoxin, leading to a decreased dose.</p> Signup and view all the answers

Cardiac glycosides are useful as rapid inotropic support in patients with decreased contractility.

<p>False</p> Signup and view all the answers

Digoxin has a wide therapeutic window.

<p>False</p> Signup and view all the answers

What are signs of Digoxin toxicity?

<p>GI signs (nausea, vomiting, diarrhea), cardiac arrhythmias, neurologic signs.</p> Signup and view all the answers

What conditions predispose a patient to digitalis toxicity?

<p>Hypokalemia and azotemia (renal insufficiency).</p> Signup and view all the answers

In digoxin toxicity, what drug would you give to treat a vagally mediated arrhythmia?

<p>Atropine.</p> Signup and view all the answers

What drug should be given to control ventricular tachyarrhythmia in digoxin toxicity?

<p>Lidocaine.</p> Signup and view all the answers

Digoxin has drug interactions with __ and __, both which increase serum [DIG].

<p>Quinidine = Increases serum Digoxin levels Verapamil = Increases serum Digoxin levels</p> Signup and view all the answers

Which class of agents are the most potent myocardial stimulants?

<p>B-adrenergic agonists.</p> Signup and view all the answers

Which B-adrenergic agonist is used most often in heart failure patients?

<p>Dobutamine.</p> Signup and view all the answers

Describe the mechanism of action of B-adrenergic agonists.

<p>Stimulate B-adrenoreceptors, converting ATP to cAMP, leading to Ca2+ influx.</p> Signup and view all the answers

Dopamine affects which types of receptors at varying doses?

<p>A (peripheral vasoconstriction), B1 (+ inotropic effect), DA (vasodilation).</p> Signup and view all the answers

What drug is ideal for inotropic support of patients with profound forward failure?

<p>Dobutamine.</p> Signup and view all the answers

What is the drug type of Dobutamine?

<p>B-adrenergic agonist.</p> Signup and view all the answers

What is the mechanism of action for phosphodiesterase inhibitors?

<p>Inhibit breakdown of cAMP, increasing Ca influx into cells.</p> Signup and view all the answers

What effects do phosphodiesterase inhibitors have in the body?

<p>Vasodilation, bronchodilation, positive inotropy.</p> Signup and view all the answers

Amrinone and milrinone are available for acute inotropic support in heart failure patients.

<p>False</p> Signup and view all the answers

What is Pimobendan's drug type and mechanism of action?

<p>Calcium sensitizing agent; sensitizes contractile apparatus to existing Ca levels.</p> Signup and view all the answers

Pimobendan has phosphodiesterase inhibitory properties in addition to Ca-sensitizing properties.

<p>False</p> Signup and view all the answers

What drug is licensed in Canada and Europe for treatment of CHF secondary to mitral valvular insufficiency in dogs?

<p>Pimobendan.</p> Signup and view all the answers

Why is Pimobendan called an 'inodilator'?

<p>Has positive inotropic effects and peripheral vasodilatory effects.</p> Signup and view all the answers

Study Notes

Inotropic Agents Overview

  • Inotropic agents enhance cardiac contractility, beneficial in compromised myocardial function.
  • Trade-offs include increased myocardial oxygen consumption and potential for arrhythmias.

Mechanism of Action

  • Most inotropic agents elevate cytosolic calcium (Ca2+) levels, facilitating greater calcium release during contraction.

Classes of Inotropes

  • Four primary classes:
    • Cardiac glycosides
    • Beta-adrenergic agonists
    • Phosphodiesterase inhibitors
    • Calcium sensitizing agents

Cardiac Glycosides

  • Two main actions:
    • Inhibit Na/K ATPase
    • Stimulate parasympathetic tone (slows sinus rate, inhibits AV node)
  • Mechanism of calcium increase: Na/K ATPase inhibition leads to increased intracellular sodium, promoting calcium influx via the Na/Ca exchanger.
  • Physiological effects include positive inotropy, negative chronotropy, natriuresis, and modulation of vascular tone depending on heart failure status.

Clinical Applications

  • Effective in systolic pump failure and atrial fibrillation.
  • Digoxin recommended formulation: elixir, dosage based on lean body mass without ascites consideration.

Pharmacokinetics

  • Minimal hepatic metabolism, primarily renal excretion; half-life increases with renal insufficiency.
  • Electrolyte disturbances, specifically hypokalemia, can increase digoxin sensitivity, necessitating lower doses.

Digoxin Toxicity

  • Symptoms: gastrointestinal issues, cardiac arrhythmias, neurological signs.
  • Conditions increasing risk: hypokalemia, azotemia (renal insufficiency).
  • Treatment for vagally mediated arrhythmias: atropine; for ventricular tachyarrhythmias: lidocaine.

Drug Interactions

  • Quinidine and verapamil raise serum digoxin levels, increasing toxicity risk.

Beta-Adrenergic Agonists

  • Most powerful myocardial stimulants with mechanisms involving cAMP pathway activation leading to enhanced calcium influx, increasing inotropy and chronotropy.

Dopamine Action

  • Acts on alpha, beta-1, and dopamine receptors with varying effects based on dosage:
    • Low doses: renal vasodilation
    • Moderate doses: increased heart rate and contractility
    • High doses: peripheral vasoconstriction

Dobutamine

  • Preferred for supportive inotropic therapy in hypotensive heart failure patients, primarily acts on beta-1 receptors with minor alpha and beta-2 activity.

Phosphodiesterase Inhibitors

  • Prevent breakdown of cAMP, leading to increased calcium availability.
  • Effects include vasodilation, bronchodilation, and positive inotropic response; high cAMP may increase risk of arrhythmias.
  • Amrinone and milrinone offer acute support with vasodilating properties.

Calcium Sensitizing Agents

  • Pimobendan enhances contractility without raising calcium levels, reducing the risk of calcium-induced arrhythmias.
  • Dual action as an 'inodilator': positive inotropic effect combined with peripheral vasodilatory action.
  • Approved in Canada and Europe for treating CHF related to mitral valvular insufficiency in dogs.

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Description

Explore the world of inotropic agents and their effects on cardiac function with this quiz. Learn how these agents increase cardiac contractility and the associated tradeoffs such as increased myocardial oxygen consumption and potential arrhythmias. Test your understanding of the mechanisms involved in their action.

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