Recommended for patients with mild to severe congestive heart failure that continue to have symptoms during ACE inhibitor, beta-blocker and diuretic therapy.
A cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system.
It acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Recommended in the treatment of patients with congestive heart failure who also have atrial fibrillation.
Improves symptoms and hospitalization rates in congestive heart failure but does not improve mortality rate.
Among hospitalized patients with heart failure with reduced ejection fraction digoxin was associated with the lower risk of hospital readmission but not all-cause mortality. (Quaker SC).
Clinical benefits are moderate, and the risk of toxicity are significant.
A substrate of P-glycoprotein.
Is linked with a significant increase in mortality in patients with atrial fibrillation (AF), according to results from a study of 4060 AF patients in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial: digoxin was associated with a 41% increase in deaths from any cause. associated with a 35% increase in cardiovascular deaths and a 61% increase in deaths from arrhythmias.
The increase in mortality in the above study occurred regardless of gender or the presence or absence of underlying heart failure (Elayi SC et al).
In a large randomized double-blind study, the Digitalis Investigation Group trial in patients with CHF and decreased left ventricular function digoxin demonstrated reduced subsequent heart failure readmissions, all cause and cardiovascular.
Digoxin increases the risk of early death in patients with heart problems, such as atrial fibrillation (AF) or congestive heart failure (CHF).
In a systematic review and meta-analysis of 19 studies published in peer-reviewed journals between 1993-2014 that looked at the effects of digoxin on death from any cause in AF and CHF patients.
In the above study of 326,426 patients (235,047 AF and 91,379 CHF patients) who were treated with digoxin, there was an overall 21% increased risk of death from any cause compared to patients who were not receiving this treatment.
In AF patients digoxin was associated with a 29% increase in risk of death, and in CHF patients digoxin was associated with a 14% increased risk of death, when compared to patients not receiving the drug.
There is a narrow dose range at which digoxin is effective and regular blood tests are required to test the levels of digoxin.
High levels have been correlated with an increased death rate in patients.
In most patients it is readily absorbed, and blood levels are very high for the first few hours after the administration.
It takes a few hours after administration to distribute from the blood to the tissues.
Digoxin should be administered a bed time and blood levels should be measured in the morning to relate serum and tissue levels.
Therapeutic serum levels are in the range of 0.5-0.9 ng/mL
Digoxin toxicity is most likely to occur when the serum digoxin level is is 1.2 g/mL or greater.
Digoxin doses should be monitored by measuring the serum digoxin level in the morning, but only at least one week after beginning or alternating doses of digoxin.
Analysis should be repeated 2-3 weeks after s patient has been on a steady digoxin dose.
In 10% of patients orally administered digoxin absorbtion is slow and reaches the distal intestines where is converted to cardiac inactive reduction products by the intestinal bacteria
Digoxin increases the risk of early death in patients with heart problems, such as atDigoxin increases the risk of early death in patients with heart problems, such as atrial fibrillation (AF) or congestive heart failure (CHF).
In a systematic review and meta-analysis of 19 studies published in peer-reviewed journals between 1993-2014 that looked at the effects of digoxin on death from any cause in AF and CHF patients.
In the above study of 326,426 patients (235,047 AF and 91,379 CHF patients) who were treated with digoxin, there was an overall 21% increased risk of death from any cause compared to patients who were not receiving this treatment.
In AF patients digoxin was associated with a 29% increase in risk of death, and in CHF patients digoxin was associated with a 14% increased risk of death, when compared to patients not receiving the drug.
There is a narrow dose range at which digoxin is effective and regular blood tests are required to test the levels of digoxin.
Digitalis intoxication separated into acute and chronic types with both phases sharing some similar symptoms.
Acute digoxin toxicity is associated with: G.I. symptoms of nausea vomiting, hyperkalemia, CNS manifestations of headache, visual changes such as halos, and confusion, associated with any arrhythmia except rapid conducted supra ventricular rhythm, and is associated with elevated serum digoxin levels.
Chronic toxicity is associated with: G.I. symptoms of nausea, vomiting, anorexia, hypokalemia or eukalemia, CNS manifestations of headache, including visual changes, halos, and confusion, malaise and seizures and is associated with the normal or elevated serum digoxin level.
Digoxin toxicity is typically associated with levels of greater than 2 ng per mill, but some patients may have toxicity would normal levels.
The most significant risk factor for digoxin toxicity is impaired renal function as digoxin undergoes significant renal elimination as an unchanged drug.
Elderly patients are at higher risk of experiencing digoxin toxicity is due to age-related impaired renal function and decrease in volume of digoxin distribution.
Monitoring renal function is essential upon initiation of the drug and periodically thereafter.
Increased risk of toxicity occurs with electrolyte imbalances including hypokalemia, hypomagnesemia, and hypercalcemia.
Drug interactions increase digoxin toxicity and with such agents as verapamil, amiodarone and clarithromycin.
Digoxin
Trade name Lanoxin
Routes of administration by mouth, intravenous.
Bioavailability 60 to 80% by mouth.
Protein binding 25%.
Metabolism by liver 16%.
Biological half-life 36 to 48 hours, with normal kidney function.
Biological half-life 3.5 to 5 days with impaired kidney function.
Excretion by kidney.
A medication used to treat various heart conditions, most frequently atrial fibrillation, atrial flutter, and heart failure.
Common side effects include breast enlargement with other side effects generally due to an excessive dose.
Side effects may include loss of appetite, nausea, trouble seeing, confusion, and an irregular heartbeat.
Greater care is required in older people and those with poor kidney function.
It is unclear if use during pregnancy is safe.
Digoxin is in cardiac glycoside family of medications.
Most common indications for digoxin are atrial fibrillation and atrial flutter with rapid ventricular response, though beta blockers and/or calcium channel blockers are often preferred.
Some evidence suggests that digoxin may increase the risk of death, though another meta-analyses report no change in mortality.
It is no longer the first choice for heart failure, but can still be useful in people who remain symptomatic despite proper diuretic and ACE inhibitor treatment.
Digoxin may increase the risk of death in heart failure.
The occurrence of adverse drug reactions is common,
Because of its narrow therapeutic index, the occurrence of adverse drug reactions is common.
The side effect of gynecomastia thought to be due to the estrogen-like steroid moiety of the digoxin molecule,[
Digoxin toxicity includes increased atrial) arrhythmias and inhibited atrioventricular conduction, paroxysmal atrial tachycardia with A-V block,.
In overdose, supportive measures are needed.
If associated arrhythmias are troublesome, or malignant hyperkalemia occurs, the specific antidote is antidigoxin.
Digoxin is usually given orally.
Can be given by IV slow IV injection in urgent situations, with heart monitoring.
Digoxin has a very long distribution half-life into the cardiac tissue, which delays its onset of action by a number of hours.
The half-life is about 36 hours for patients with normal renal function
It is given once daily, usually in 125-μg or 250-μg doses.
Digoxin elimination is mainly by renal excretion.
Excretion involves P-glycoprotein, which leads to significant clinical interactions with P-glycoprotein inhibitor drugs.
Effective plasma levels for congestive heart failure, levels between 0.5 and 1.0 ng/ml are recommended, as higher levels may be associated with increased mortality rates.
For heart rate control in atrial fibrillation, plasma levels are less defined and are generally titrated to a goal heart rate, but digoxin levels are considered therapeutic for heart rate control between 0.5 and 2.0 ng/ml.
In suspected toxicity or ineffectiveness, digoxin levels should be monitored. and potassium levels also need to be closely followed.
Quinidine, verapamil, and amiodarone increase plasma levels of digoxin by displacing tissue binding sites and depressing renal digoxin clearance.
Some studies suggest there is significantly higher risk of death for women than men on digoxin.
Primary mechanism of action involves inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase), in the myocardium.
This inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase), increases intracellular sodium levels, resulting in a reversal of the action of the sodium-calcium exchanger.
The sodium-calcium exchanger normally imports three extracellular sodium ions into the cell and transports one intracellular calcium ion out of the cell.
The reversal of this exchange process causes an increase in the intracellular calcium concentration that is available to the contractile proteins, lengthening phase 4 and phase 0 of the cardiac action potential, which leads to a decrease in heart rate.
Increased amounts of Ca2+ also leads to increased storage of calcium in the sarcoplasmic reticulum, causing a corresponding increase in the release of calcium during each action potential, increasing contractility of the heart without increasing heart energy expenditure.
The main drug effects of digoxin are on the heart.
Digoxin exerts a mechanical effect as it increases myocardial contractility.
The duration of the contractile response is only slightly increased.
By slowing down the conduction in the AV node and increasing its refractory period, digoxin can reduce the ventricular rate, and increase diastolic filling time.
It improved pumping function of the heart by improving filling.
Overall it decreases the heart rate while blood pressure is increased, resulting in a net increase in stroke volume,
Use leads to increased tissue perfusion.
It causes the myocardium to work more efficiently, with optimal hemodynamics and an improved ventricular function curve.
Can cause an initial increase in action potential, followed by a decrease as the K+ conductance increases due to increased intracellular amounts of Ca2+ ions.
Decreases the refractory period of the atria and ventricles, while it increases in the sinoatrial and AV nodes.
Associated with a negative resting membrane potential, leading to increased irritability.
Increases vagal activity, and decreases heart rate by slowing depolarization of pacemaker cells in the AV node.
Its negative chronotropic effects are synergistic with the direct effect on cardiac pacemaker cells.
Conduction velocity increases in the atria, but decreases in the AV node, and its effect upon Purkinje fibers and ventricles is negligible.
Automaticity is also increased in the atria, AV node, Purkinje fibers, and ventricles.
ECG changes seen in patient taking digoxin include: increased PR interval which is due to decreased AV conduction, and a shortened QT interval, the T wave may be inverted and accompanied by ST depression, and it may cause AV junctional rhythm and ectopic beats resulting in ventricular tachycardia and fibrillation.
Digoxin improves hemodynamics, restores angiotensin levels and decreases sympathetic discharge, causing indirect vasodilation.
Digoxin also affects the kidney by increasing renal blood flow and increasing glomerular filtration rate.
A mild diuretic effect is seen only in heart failure.