Digoxin
Introduction
Digoxin is only agent in the family of cardiac glycosides and comes from digitalis plant. Digitalis glycosides have a low
therapeutic index with only a small difference between therapeutic dose and doses that are toxic or even fatal.
Mechanism of action
a- Regulation of cytosolic calcium concentration:
By inhibiting the Na+/K+-adenosine triphosphates (ATPase) enzyme, digoxin reduces the ability of the myocyte to actively
pump Na from the cell. This ultimately results in a small but physiologically important increase in free Ca²+, thereby
leading. To increased cardiac contractility.
b-Increased contractility of the cardiac muscle:
Digoxin increases the force of cardiac contraction, causing cardiac output to more closely resemble that of the normal
heart. Vagal tone is also enhanced, so both heart rate and myocardial oxygen demand decrease. Digoxin slows
conduction velocity through the AV node, making it useful for atrial fibrillation.
C-Neurohormonal inhibition:
Although the exact mechanism of this effect has not been elucidated, low-dose digoxin inhibits sympathetic activation,
with minimal effects on contractility. This effect is the reason a lower serum drug concentration is targeted In HFrEF.
Therapeutic uses:
Digoxin therapy is indicated in patients with HFrEF who are symptomatic on optimal HF pharmacotherapy. A low serum
drug concentration of digoxin (0.5 to 0.8 ng/mL) is beneficial in HFrEF.
Pharmacokinetics:
Digoxin is available in oral and injectable formulations. It has a large volume of distribution, because it accumulates in
muscle. The dosage is based on lean body weight. In acute situations, such as symptomatic atrial fibrillation, a loading
dose regimen is used. Digoxin has a long half-life of 30 to 40 hours. It is mainly eliminated intact by the kidney, requiring
dose adjustment in renal dysfunction.
Adverse effects:
At low serum drug concentrations, digoxin is well tolerated. However, it has a very narrow therapeutic index. Anorexia,
nausea, vomiting, blurred vision, or yellowish vision may “be initial indicators of toxicity. When Na+/K+-ATPase is
markedly inhibited by digoxin, the resting membrane potential may increase, which makes the membrane more excitable,
increasing the risk of arrhythmias.
Toxicology
Decreased levels of serum potassium (hypokalemia) predispose a patient to digoxin toxicity, because digoxin normally
competes with potassium for the same binding site on the Na K-ATPase pump. With the use of a lower serum drug
concentration in HFrEF, toxic levels are infrequent.
Drug interactions
Digoxin is a substrate of P-gp, and inhibitors of P-gp, such as clarithromycin, verapamil and amiodarone, can significantly
increase digoxin levels, necessitating a reduced dose of digoxin. Digoxin should also be used with caution with other
drugs that slow AV conduction, such as beta blockers, verapamil.
Dosage forms
Digoxin is available in both oral and injectable forms.
Brand name: Lanoxin Tablet: 250 mg
Injection: 0.5 mg/2ml. A clear, colourless, sterile aqueous solution containing digoxin BP 250 mg per mil and supplied in a
2ml ampoule.
Pregnancy category: US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect
on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of
the drug in pregnant women despite potential risks.
