Digitoxin is acardiac glycoside used for the treatment ofheart failure and certain kinds ofheart arrhythmia. It is aphytosteroid and is similar instructure and effects todigoxin, though the effects are longer-lasting. Unlike digoxin, which is eliminated from the body via the kidneys, it is eliminated via the liver, and so can be used in patients with poor or erratic kidney function. While several controlled trials have shown digoxin to be effective in a proportion of patients treated for heart failure, the evidence base for digitoxin is not as strong, although it is presumed to be similarly effective.[1]
Digitoxin is used for the treatment of heart failure, especially in people with impaired kidney function. It is also used to treat certain kinds ofheart arrhythmia, such asatrial fibrillation.[2][3]
Digitoxin exhibits similar toxic effects todigoxin, namely:anorexia,nausea, vomiting, diarrhea, confusion, visual disturbances, and cardiacarrhythmias. Antidigoxinantibody fragments, the specific treatment for digoxin poisoning, are also effective in serious digitoxin toxicity.[4]
Digitoxin inhibits thesodium-potassium ATPase in heart muscle cells, resulting in increased force of contractions (positiveinotropic), reduced speed of electric conduction (negativedromotropic), increased excitability (positivebathmotropic), and reduced frequency of heartbeat (negativechronotropic).[3]
The drug is almost completely absorbed from the gut. When in the bloodstream, 90 to 97% are bound toplasma proteins. Digitoxin undergoesenterohepatic circulation. It ismetabolized in part by CYP3A4; metabolites includedigitoxigenin,digoxin (>2%), andconjugate esters. In healthy people, 60% are eliminated via the kidneys and 40% via the faeces. In people with impaired kidney function, elimination via the faeces is increased. Thebiological half-life is 7 to 8 days except when kidneyand liver functions are impaired, in which case it is usually longer.[3][5]
The first description of the use offoxglove dates back to 1775.[6] For quite some time, the active compound was not isolated.Oswald Schmiedeberg was able to obtain a pure sample in 1875. The modern therapeutic use of this molecule was made possible by the works of the pharmacist and the French chemistClaude-Adolphe Nativelle (1812–1889). The first structural analysis was done byAdolf Otto Reinhold Windaus in 1925, but the full structure with an exact determination of the sugar groups was not accomplished until 1962.[7][8]
Digitoxin and related cardenolides display anticancer activity against a range of humancancer cell lines in vitro but the clinical use of digitoxin to treatcancer has been restricted by its narrowtherapeutic index.[10][11] Digitoxinglycorandomization led to the discovery of noveldigitoxigenin neoglycosides which displayed improved anticancer potency and reduced inotropic activity (the perceived mechanism of general toxicity).[12]
^Kurowski V, Iven H, Djonlagic H (1992). "Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies".Intensive Care Medicine.18 (7):439–42.doi:10.1007/BF01694351.PMID1469187.S2CID2324996.
Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P (June 2001). "Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells".Anti-Cancer Drugs.12 (5):475–83.doi:10.1097/00001813-200106000-00009.PMID11395576.S2CID19894541.
Hippius M, Humaid B, Sicker T, Hoffmann A, Göttler M, Hasford J (August 2001). "Adverse drug reaction monitoring--digitoxin overdosage in the elderly".International Journal of Clinical Pharmacology and Therapeutics.39 (8):336–43.doi:10.5414/cpp39336.PMID11515708.
Comparing the Toxicity of Digoxin and Digitoxin in a Geriatric Population: Should an Old Drug Be Rediscovered? onMedscape(registration required), a convenience link from theoriginal.(subscription required)
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