Positive inotropic agents - Digoxin

Question 1

Inotropic drugs - 3 groups

Answer 1

Digitalis glycoside.
Adrenoceptor agonist.
Phosphodiesterase inhibitor

Question 2

Effects of inotropic drugs

Answer 2

Increase cardiac contractility

Question 3

Digitalis glycoside - 1 drug + its adm

Answer 3

Digoxin - adm orally

Question 4

The inotropic drugs most often used for heart failure (3 drugs + their groups)

Answer 4

Digoxin - digitalis glycoside.
Dobutamine - β-adrenoceptor agonist.
Milrinone - Phosphodiesterase inhibitor.

Question 5

Digoxin - dosing

Answer 5

Low therapeutic index, serum level should be 0.5-2ng/ml. (high toxicity of this drug)

Question 6

Digoxin - MOA

Answer 6

Inhibition of Na/K-ATPase pump in plasma membrane causes increased intracellular Na. This increases the activity of the Na/Ca exchanger, and increases the concentration of Ca intracellularly. This further stimulates Ca release from SR. Net result: increased stroke volume and CO.

Question 7

Digoxin - effects

Answer 7

Positive inotropic effect (increased contractile force).
Negative chronotropic effect (decreased HR).
Negative dromotropic effect (decreased conduction velocity).
Increased parasympathetic tone.
Reduced sympathetic tone.

Question 8

Digoxin - effects of increased vagal tone.

Answer 8

Increased parasympathetic tone: decreases HR and AV node conduction while increasing the AV refractory period.

Question 9

Digoxin - effects on cardiac electrophysiology

Answer 9

Increase abnormal impulse formation by spontaneous afterdepolarizations (premature/coupled beats and tachycardia).
Decreased QT interval (shortening of ventricular action potential and accelerating repolarization).
Increased PR interval (reduced AV node conduction).
ST-depression: hockeystick configuration.

Question 10

Digoxin - adverse effects

Answer 10

Toxicity (anorexia, nausea, vomiting are earliest signs).
Arrhythmias: AV block, tachyarrhythmias, atrial tachycardia with 2:1 or 3:1 AV block, ventricular arrythmias.
Hypokalemia: precipitate arrhythmias.
Blurred vision, chromatopsia (yellow, green, blue), precipitate seizures.
Gynecomastia

Question 11

Digoxin - interactions

Answer 11

Antacids and cholestyramine: decrease absorption.
Diltiazem, verapamil, quinidine: increase serum levels and contributes to digoxin toxicity. (50% of the digoxin dose should be given).
Loop and thiazide diuretics: hypokalemia (precipitate toxicity, arrhythmias).

Question 12

Why may hypokalemia precipitate digoxin toxicity?

Answer 12

Decreased potassium increases the binding of digitalis to the sodium pumps.

Question 13

Digoxin - indications

Answer 13

Heart failure with atrial arrhythmias.

Systolic heart failure.

Question 14

Why is digoxin not used to treat diastolic heart failure?

Answer 14

Because diastolic heart failure usually is not connected to impaired contractility.

Question 15

Does digoxin prolong survival?

Answer 15

No

Question 16

Does digoxin reduce symptoms?

Answer 16

Yes

Question 17

Digoxin is often used in combination with:

Answer 17

Angiotensin inhibitors, diuretics, β-blockers, aldosterone antagonists.

Question 18

Treatment of digoxin toxicity

Answer 18

Digoxin immune Fab (IV). This drug reverse toxicity by binding to digoxin