DIGOXIN

Dr. Amlendra Phase-A Resident (BSMMU)

About Digoxin

• It is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata.

• Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin

• It is widely used in the treatment of various heart conditions namely atrial fibrillation, atrial flutter and sometimes heart failure that cannot be controlled by other medication

Pharmacological Class :- Cardiac Glycoside

Therapeutic Class :- Inotrope, antiarrhythmic

Action

• The main pharmacological effects of digoxin are on the heart

• It has mechanical effects as it increases myocardial contractility; however, the duration of the contractile response is just slightly increased

• Overall, the heart rate is decreased, while blood pressure increases as the stroke volume is increased, leading to increased tissue perfusion

• Myocardial efficiency is due to improved hemodynamics, and the ventricular function curve is improved.

Cont..

• Other, electrical effects are an initial brief increase in action potential, followed by a decrease as the K+ conductance increases due to an increased intracellular amounts of Ca2+ ions

• The refractory period of the atria and ventricles is decreased, while it increases in the sinoatrial and AV nodes

• A less negative resting membrane potential is made, leading to increased excitability

Cont..

• Slight vasodilation is seen in heart failure. This effect is contrary to effects that should be seen as a result of increased intracellular calcium levels, but this occurs since digoxin improves hemodynamics, which leads to restored angiotensin levels and decreased sympathetic discharge, causing indirect vasodilation.

• It also affects the kidney by increased renal blood flow and increased glomerular filtration rate. A mild diuretic effect is seen only in heart failure .

Pharmacokinetics

• About 70 to 80% of an oral dose of digoxin is absorbed, mainly in the proximal part of the small intestine. The degree of binding to serum albumin is 20 to 30%. Digoxin is extensively distributed in the tissues, as reflected by the large volume of distribution. High concentrations are found in the heart and kidneys, but the skeletal muscles form the largest digoxin storage.

• The half-life of elimination varies between 26 and 45 hours

Cont..

• The main route of elimination is renal excretion of digoxin, which is closely correlated with the glomerular filtration rate. In addition, some tubular secretion and perhaps tubular reabsorption occurs. Nearly all of the digoxin in the urine is excreted unchanged, with a small part as active metabolites. The clinical significance of dihydrodigoxin as a metabolite remains to be resolved. About 25 to 28% of digoxin is eliminated by nonrenal routes. Biliary excretion may rise up to 30% of a given dose, but the enterohepatic cycle seems to be of minor importance.

Indication

• Heart Failure

• Tachyarrhythmias

• Atrial Fibrillation

• Atrial Flutter

• Paroximal atrial tachycardia

Dosing

Administration

• Administer slowly by direct IV injection over minimum of 5 minutes (longer if given undiluted)

• Do not administer if precipitate present

• Drug is severe skin irritant when given IV/IM and may cause severe local skin reaction with possible sloughing

Contraindication and Precaution

• Hypersensitivity

• Uncontrolled Ventricular Arrhythmias

• AV block

• Constrictive Pericarditis

• Idiopathic Hypertrophic Subaortic Stenosis

Use cautiously in

• Renal & Hepatic impairment• Electrolyte imbalance • Myocardial Infarction• Thyroid Disoder • Obesity • Elderly Patient• Pregnancy• Breastfeeding infant

Adverse Effects

• Dizziness (4.9%)

• Mental disturbances (4.1%)

• Diarrhea (3.2%)

• Headache (3.2%)

• Nausea (3.2%)

• Vomiting (1.6%)

• Maculopapular rash (1.6%)

<1%

• Anorexia

• Cardiac dysrhythmia

• Arrhythmia in children (consider a toxicity)