2712 Digoxin Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. It is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and congestive heart failure that cannot be controlled by other medication. Digoxin preparations are commonly marketed under the trade name Lanoxin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) Digoxin is a cardiotonic glycoside obtained mainly from Digitalis lanata; It consists of three sugars and the aglycone digoxigenin. Digoxin binds to a site on the extracellular aspect of the of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This is a different mechanism from that of catecholamines. Owing to its narrow therapeutic index (the margin between effectiveness and toxicity), side effects of digoxin are inevitable. Nausea, vomiting and GIT upset are common, especially in higher doses. Decreased conduction in the AV node can lead to AV blocks, increased intracellular Ca2+ causes a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation. An often described but rarely seen side effect of digoxin is a disturbance of color vision (mostly yellow and green color) called xanthopsia. 20830-75-5 2724385 C41H64O14 780.429610 Colorless to white crystals; or white crystalline powder (A308). 217-221°C 64.8 mg/L (at 25°C) Injestion or dermal contact. (L1817) Absorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets). Digoxin binds to a site on the extracellular aspect of the alpha-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes) and decreases its function. This causes an increase in the level of sodium ions in the myocytes. This effect causes an increase in the length the cardiac action potential, which when combined with the effects of digoxin on the parasympathetic nervous system, lead to a decrease in heart rate. Increased amounts of calcium are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This leads to increased contractility of the heart. Digoxin also increases vagal activity via its action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. (L1247) Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. Route of Elimination: Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Half Life: 3.5 to 5 days LD₅₀ = 7.8 mg/kg (orally in mice). 2B, possibly carcinogenic to humans. (L135) For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure. Digoxin is a plant toxin found in the foxglove plant (Digitalis lanata). It is used as a drug to treat various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure. (L1247) Digoxin mainly affects the heart. (L1247) Adverse affects of digoxin include loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities. (L1247) Treatment of dioxin overdose includes supportive measure and administration of the antidote, antidigoxin (DIGIBIND). Toxicity can also be treated with higher than normal doses of potassium. (L1247) 2009-07-15T20:45:04Z 2014-12-24T20:25:49Z Digoxin C06956 108950 177720 309801 4551 Digoxin DB00390 DGX true [H][C@@]1(CC[C@]2(O)[C@]3([H])CC[C@]4([H])C[C@]([H])(CC[C@]4(C)[C@@]3([H])C[C@@]([H])(O)[C@]12C)O[C@@]1([H])C[C@]([H])(O)[C@]([H])(O[C@@]2([H])C[C@]([H])(O)[C@]([H])(O[C@@]3([H])C[C@]([H])(O)[C@]([H])(O)[C@@]([H])(C)O3)[C@@]([H])(C)O2)[C@@]([H])(C)O1)C1=CC(=O)OC1 C41H64O14 InChI=1S/C41H64O14/c1-19-36(47)28(42)15-34(50-19)54-38-21(3)52-35(17-30(38)44)55-37-20(2)51-33(16-29(37)43)53-24-8-10-39(4)23(13-24)6-7-26-27(39)14-31(45)40(5)25(9-11-41(26,40)48)22-12-32(46)49-18-22/h12,19-21,23-31,33-38,42-45,47-48H,6-11,13-18H2,1-5H3/t19-,20-,21-,23-,24+,25-,26-,27+,28+,29+,30+,31-,33+,34+,35+,36-,37-,38-,39+,40+,41+/m1/s1 InChIKey=LTMHDMANZUZIPE-PUGKRICDSA-N 780.9385 780.429606756 Exogenous Solid 1.26 HMDB01917 CHEMBL1751 2006532 <p>Wolfgang Voigtlander, Fritz Kaiser, Wolfgang Schaumann, Kurt Stach, &#8220;Preparation of C22-alkyl derivative of digoxin.&#8221; U.S. Patent US3981862, issued October, 1972.</p>