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Questions and Answers
What are the tradeoffs to the effect of inotropic agents?
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?
By what mechanism do most inotropic agents increase cardiac contractility?
Increasing cytosolic Ca2+ levels.
What are the four general classes of inotropes?
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?
What two actions do cardiac glycosides have?
How do cardiac glycosides increase intracellular Ca2+ levels?
How do cardiac glycosides increase intracellular Ca2+ levels?
What is the result of cardiac glycosides stimulating parasympathetic tone?
What is the result of cardiac glycosides stimulating parasympathetic tone?
Name three physiological effects of Cardiac Glycosides.
Name three physiological effects of Cardiac Glycosides.
In what situations do you use cardiac glycosides?
In what situations do you use cardiac glycosides?
Which formulation of Digoxin is most clinically useful?
Which formulation of Digoxin is most clinically useful?
How is Digoxin metabolized?
How is Digoxin metabolized?
How do electrolyte disturbances affect the necessary Digoxin dose?
How do electrolyte disturbances affect the necessary Digoxin dose?
Cardiac glycosides are useful as rapid inotropic support in patients with decreased contractility.
Cardiac glycosides are useful as rapid inotropic support in patients with decreased contractility.
Digoxin has a wide therapeutic window.
Digoxin has a wide therapeutic window.
What are signs of Digoxin toxicity?
What are signs of Digoxin toxicity?
What conditions predispose a patient to digitalis toxicity?
What conditions predispose a patient to digitalis toxicity?
In digoxin toxicity, what drug would you give to treat a vagally mediated arrhythmia?
In digoxin toxicity, what drug would you give to treat a vagally mediated arrhythmia?
What drug should be given to control ventricular tachyarrhythmia in digoxin toxicity?
What drug should be given to control ventricular tachyarrhythmia in digoxin toxicity?
Digoxin has drug interactions with __ and __, both which increase serum [DIG].
Digoxin has drug interactions with __ and __, both which increase serum [DIG].
Which class of agents are the most potent myocardial stimulants?
Which class of agents are the most potent myocardial stimulants?
Which B-adrenergic agonist is used most often in heart failure patients?
Which B-adrenergic agonist is used most often in heart failure patients?
Describe the mechanism of action of B-adrenergic agonists.
Describe the mechanism of action of B-adrenergic agonists.
Dopamine affects which types of receptors at varying doses?
Dopamine affects which types of receptors at varying doses?
What drug is ideal for inotropic support of patients with profound forward failure?
What drug is ideal for inotropic support of patients with profound forward failure?
What is the drug type of Dobutamine?
What is the drug type of Dobutamine?
What is the mechanism of action for phosphodiesterase inhibitors?
What is the mechanism of action for phosphodiesterase inhibitors?
What effects do phosphodiesterase inhibitors have in the body?
What effects do phosphodiesterase inhibitors have in the body?
Amrinone and milrinone are available for acute inotropic support in heart failure patients.
Amrinone and milrinone are available for acute inotropic support in heart failure patients.
What is Pimobendan's drug type and mechanism of action?
What is Pimobendan's drug type and mechanism of action?
Pimobendan has phosphodiesterase inhibitory properties in addition to Ca-sensitizing properties.
Pimobendan has phosphodiesterase inhibitory properties in addition to Ca-sensitizing properties.
What drug is licensed in Canada and Europe for treatment of CHF secondary to mitral valvular insufficiency in dogs?
What drug is licensed in Canada and Europe for treatment of CHF secondary to mitral valvular insufficiency in dogs?
Why is Pimobendan called an 'inodilator'?
Why is Pimobendan called an 'inodilator'?
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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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