Positive inotropic medications

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Positive inotropic medications

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Positive inotropic medications

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In a large clinical trial, patients with heart failure with reduced ejection fraction (HFrEF) were randomized to study medications A and B. The average left ventricular ejection fraction of study subjects was 30%. Most patients in both groups were concomitantly treated with agents A and B. In the long term, all-cause mortality curves are shown below. The solid line represents agent A, whereas the dashed line represents agent B. The differences between the curves were statistically significant. The dashed line on the graph represents which of the following drugs?
 

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Anti-digoxin Fab fragments p. 249

Digoxin p. NaN

antidote for p. 120

contractility effects of p. 292, 293

for dilated cardiomyopathy p. 317

sodium-potassium pump inhibition p. 47

therapeutic index of p. 235

toxicity treatment p. 363

Digoxin immune Fab p. 120

Vision change/loss

digoxin p. NaN

Transcript

Positive inotropic medications, as their name implies, are a diverse group of medications that increase the strength of heart muscle contraction.

As a result, they increase the stroke volume and thus, the cardiac output.

Positive inotropic medications include cardiac glycosides, like digoxin; beta agonists, like dobutamine; and phosphodiesterase inhibitors, like milrinone.

They are used in conditions where the heart can’t pump enough blood to the body’s tissues, like in systolic heart failure.

Alright, the heart needs to squeeze out a certain volume of blood each minute, called the cardiac output, which can be rephrased as the heart rate multiplied by the stroke volume, which is the volume of blood squeezed out with each heartbeat.

Okay, now the stroke volume depends on the preload, or the amount of blood that returns to the heart; the afterload, or peripheral resistance; and the strength of the contraction, or contractility, of the cardiac muscle.

Now, muscle contraction is initiated with an action potential which modifies receptors allowing calcium ions to flow from the sarcoplasmic reticulum into the sarcoplasm.

This allows myosin heads to bind to the actin.

These two proteins are ultimately responsible for cell contraction.

In order for a muscle to relax, calcium ions must be pumped back into the sarcoplasmic reticulum.

When the frequency of stimulation is increased, more calcium ions accumulate in the sarcoplasm, and the strength of contraction increases.

Alright, now there are conditions in which the strength of the heart’s contraction is impaired, and the heart can’t pump out enough blood to meet the body’s demands, this is called heart failure.

Summary

Positive inotropic medications are medications that increase the force of muscle contraction of the heart, resulting in an increased cardiac output. Examples of positive inotropic medications include digoxin, dobutamine, and milrinone. These medications are generally used to treat systolic heart failure, cardiogenic shock, and other heart-related conditions.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Digoxin in Heart Failure with a Reduced Ejection Fraction: A Risk Factor or a Risk Marker?" Cardiology (2016)
  5. "Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome" Cochrane Database of Systematic Reviews (2018)
  6. "Treatments targeting inotropy" European Heart Journal (2018)
  7. "Therapeutic achievements of phosphodiesterase inhibitors and the future" European Heart Journal (1989)
Elsevier

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