Digoxin

Digoxin, sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is taken by mouth or by injection into a vein.The 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.The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Gynaecomastia (enlargement of breast tissue) is mentioned in many textbooks as a side effect, thought to be due to the estrogen-like steroid moiety of the digoxin molecule, but when systematically sought, the evidence for this is equivocal as of 2005.The combination of increased (atrial) arrhythmogenesis and inhibited atrioventricular (AV) conduction (for example paroxysmal atrial tachycardia with AV block – so-called 'PAT with block') is said to be pathognomonic (that is, diagnostic) of digoxin toxicity.In overdose, the usual supportive measures are needed. If arrhythmias prove troublesome, or malignant hyperkalemia occurs (inexorably rising potassium level due to paralysis of the cell membrane-bound, ATPase-dependent Na/K pumps), the specific antidote is antidigoxin (antibody fragments against digoxin, trade names Digibind and Digifab).Digoxin's primary mechanism of action involves inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase), mainly in the myocardium. This inhibition causes an increase in intracellular sodium levels, resulting in decreased activity of the sodium-calcium exchanger, which normally imports three extracellular sodium ions into the cell and transports one intracellular calcium ion out of the cell. The reversal of this exchanger causes an increase in the intracellular calcium concentration that is available to the contractile proteins. Increased intracellular calcium lengthens 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. This leads to increased contractility (the force of contraction) of the heart without increasing heart energy expenditure.Derivatives of plants of genus Digitalis have a long history of medical use. The English physician William Withering is credited with the first published description of the use of Digitalis derivatives in his 1785 book An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases. It effects were first explained by Arthur Robertson Cushny.Charles Cullen admitted in 2003 to killing as many as 40 hospital patients with overdoses of heart medication—usually digoxin—at hospitals in New Jersey and Pennsylvania over his 19-year career as a nurse. On March 10, 2006, he was sentenced to 18 consecutive life sentences and is not eligible for parole. tablets of Caraco brand Digoxin, USP, 0.125 mg, and Digoxin, USP, 0.25 mg, distributed prior to March 31, 2009, which are not expired and are within the expiration date of September, 2011, are being voluntarily recalled to the consumer level. The tablets are being recalled because they may differ in size and therefore could have more or less of the active ingredient, digoxin.