Digox

Digoxin.

Each tablet contains: Digoxin 250 mcg.

Pharmacologic Category: Digitalis Glycoside.
Pharmacology: Pharmacodynamics: Digoxin directly increases contractility of the myocardium and primarily acts by inhibiting the action of adenosine triphosphatase, and Na⁺/K⁺ exchange activity. It augments calcium ion influx and increases calcium availability at the excitation-contraction coupling. The potency of digoxin may be enhanced when extracellular potassium concentration is low, with hyperkalaemia having opposite effect. Digoxin inhibits the Na⁺-K⁺ exchange mechanism on cells of the autonomic nervous system, stimulating them to exert indirect cardiac activity. Increases in efferent vagal impulses result in reduced sympathetic tone and diminished impulse conduction rate through the atria and atrio-ventricular node and reduces ventricular rate.
Pharmacokinetics: The absorption of Digoxin from the gastrointestinal tract is variable depending upon the formulation used. About 70% of a dose is absorbed from the tablets which comply with BP or USP specifications, 80% is absorbed from elixir, and over 90% is absorbed from the liquid-filled soft gelatin capsules. The generally accepted therapeutic plasma concentration range is 0.5 to 2.0 nanograms/mL but there is considerable interindividual variation. Digoxin has a large volume of distribution and is widely distributed in tissues, including the heart, brain, erythrocytes, and skeletal muscle. The concentration of Digoxin in the myocardium is considerably higher than in plasma. From 20% to 30% is bound to plasma proteins. Digoxin has been detected in cerebrospinal fluid and breast milk; it also crosses the placenta. It has an elimination half-life of 1.5 to 2 days.
Digoxin is mainly excreted unchanged in the urine by glomerular filtration and tubular secretion; reabsorption also occurs. Extensive metabolism has been reported in a minority of patients. Excretion of Digoxin is proportional to the glomerular filtration rate. After intravenous injection 50% to 70% of the dose is excreted unchanged. Digoxin is not removed from the body by dialysis, and only small amounts are removed by exchange transfusion and during cardiopulmonary by-pass.

Digoxin is a cardiac glycoside used in the management of supraventricular arrhythmias, particularly atrial fibrillation, and in heart failure.
The principal actions of Digoxin are an increase in the force of myocardial contraction (positive inotropic activity) and a reduction in the conductivity of the heart, particularly in conduction through the atrioventricular (AV) node. Digoxin also has a direct action on vascular smooth muscle and indirect effects mediated primarily by the autonomic nervous system, and particularly by an increase in vagal activity. These are also reflex alterations in autonomic activity due to the effects on the circulation. Overall, these actions result in positive inotropic effects, and decreased AV nodal activity.

If rapid digitalization is required then a loading dose is given to allow for the large volume of distribution. A total loading dose of 750 to 1500 micrograms of Digoxin may be given by mouth during the initial 24-hour period, either as a single dose, or when there is less urgency or greater risk of toxicity, in divided doses at 6-hourly intervals. In some patients, for example those with mild heart failure, a loading dose may not be necessary, and digitalization may be achieved more slowly with doses of 250 micrograms once or twice daily. The usual maintenance dose of Digoxin is 125 to 250 micrograms by mouth daily, but may range from 62.5 to 500 micrograms daily.
Dose should be reduced in patients with renal impairment.
Or as prescribed by the physician.

The main symptoms of toxicity are heart rhythm disturbances and gastrointestinal symptoms which may happen before heart rhythm disturbances. Gastrointestinal symptoms include loss of appetite, nausea and vomiting. Other symptoms of toxicity include dizziness, fatigue a general feeling of being unwell and various neurological disturbances including visual disturbances (more yellow-green than usual). The neurological and visual symptoms may persist even after other signs of toxicity have been resolved. In chronic toxicity, non-heart related symptoms. Such as weakness and a general feeling of being unwell.
After recent ingestion, such as accidental or deliberate self-poisoning, the load available for absorption may be reduced by gastric lavage. Gastric lavage increases vagal tone and may precipitate or worsen arrhythmias. Consider pre-treatment with atropine if gastric lavage is performed. Treatment with digitalis Fab antibody usually renders gastric lavage unnecessary. If hypokalaemia is present, it should be corrected with potassium supplements either orally or intravenously, depending on the urgency of the situation. Before administering potassium in digoxin overdose the serum potassium level must be known. Bradyarrhythmias may respond to atropine but temporary cardiac pacing may be required. Ventricular arrhythmias may respond to lidocaine or phenytoin.

Digoxin is generally contraindicated in patients with hypertrophic obstructive cardiomyopathy unless there is severe cardiac failure, since the outflow obstruction may be worsened. It is also contraindicated in patients with the Wolff-Parkinson-White syndrome or other evidence of an accessory pathway, especially if it is accompanied by atrial fibrillation, since ventricular tachycardia or fibrillation may be precipitated.

Digoxin should be used with caution in partial heart block since complete heart block may be induced; it should also be used with care in sinus node disorders. Caution is also required in acute myocarditis (such as rheumatic carditis) in acute myocardial infarction, in advanced heart failure, and in severe pulmonary disease, due to increased myocardial sensitivity.

Pregnancy: The use of digoxin in pregnancy is not contraindicated, although the dosage may be less predictable in pregnant than in non-pregnant women, with some requiring and increased dosage of digoxin during pregnancy. As with all drugs, use should be considered only when the expected clinical benefit of treatment to the mother outweighs any possible risk to the developing fetus.
Despite extensive antenatal exposure to digitalis preparations, no significant adverse effects have been observed in the fetus or neonate when maternal serum digoxin concentrations are maintained within normal range. Although it has been speculated that a direct effect of digoxin on the myometrium may result in relative prematurity and low birthweight, a contributing role of the underlying cardiac disease cannot be excluded. Maternally administered digoxin has been successfully used to treat fetal tachycardia and congestive heart failure.
Adverse fetal effects have been reported in mothers with digitalis toxicity.
Lactation: Although digoxin is excreted in breast milk, the quantities are minute and breastfeeding is not contraindicated.

Digoxin and other glycosides commonly produce adverse effects because the margin between the therapeutic and toxic doses is small; plasma concentrations of Digoxin in excess of 2 nanograms / mL are considered to be an indication that the patient is at special risk although there is considerable interindividual variation. There have been many fatalities, particularly due to cardiac toxicity.
Nausea, vomiting and anorexia may be among the earliest symptoms of Digoxin toxicity or overdosage; diarrhea and abdominal pain may occur. Certain neurological effects are also common symptoms of Digoxin overdosage and include headache, facial pain, fatigue, weakness, dizziness, drowsiness, disorientation, mental confusion, bad dreams and more rarely delirium, acute psychoses, and hallucinations.
Visual disturbances including blurred vision may occur; color vision may be affected with objects appearing yellow or, less frequently, green, red, brown, blue or white. Hypersensitivity reactions are rare; thrombocytopenia has been reported. The cardiac glycosides may have some estrogenic activity and occasionally cause gynecomastia at therapeutic doses. The most serious side effects are those on the heart. Toxic doses may cause or aggravate heart failure.

There may be interactions between Digoxin and drugs that after its absorption, interfere with its excretion, or have additive effects on the myocardium. Drugs that cause electrolyte disturbances increase the risk of toxicity from cardiac glycosides. Thiazides and loop diuretics cause hypokalemia and also hypomagnesemia which may lead to cardiac arrhythmias. Other causes of hypokalemia include treatment with corticosteroids, beta-2 agonists (such as salbutamol), amphotericin B, sodium polystyrene sulfonate, carbenoxolone and dialysis. Hypercalcemia may also increase toxicity and intravenous use of calcium salts is best avoided in patients taking cardiac glycosides. Serum-digoxin concentrations may be significantly increased by quinidine, amiodarone and propafenone and reduction of Digoxin dosage may be required. Other antiarrhythmics may have additive effects on the myocardium increasing the likelihood of adverse effects; beta blockers may potentiate bradycardia due to Digoxin. Calcium-channel blockers may increase Digoxin concentrations.
Digoxin is a substrate for P-glycoprotein and interactions may occur with drugs that affect P-glycoprotein action.

Cardiac Drugs

C01AA05 - digoxin ; Belongs to the class of digitalis glycosides. Used in the treatment of heart failure.

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