Digitoxin
Intravenous injection | |
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| Pharmacokinetic data | |
| Bioavailability | 98–100% (oral) |
| Protein binding | 90–97% |
| Metabolism | Liver (CYP3A4) |
| Elimination half-life | 7–8 days |
| Excretion | 60% via urine, 40% via faeces |
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Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, 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]
Medical uses
Digitoxin is used for the treatment of heart failure, especially in people with impaired kidney function. It is also used to treat certain kinds of
Contraindications
Contraindications include[3]
- problems with the heart rhythm, such as severe bradycardia (slow heartbeat), ventricular tachycardia (fast heartbeat caused by the ventricles), ventricular fibrillation, or first- to second-degree atrioventricular block,
- and certain hypercalcemia(high calcium).
Adverse effects and toxicity
Digitoxin exhibits similar toxic effects to
Interactions
Drugs that can increase digitoxin toxicity include:[3]
- calcium
- substances that lower potassium or magnesium levels, such as diuretics and corticosteroids
- inhibitors of the liver enzyme CYP3A4, which slow down digitoxin metabolism; examples are the antibiotic clarithromycin, the antifungal itraconazole, and grapefruit juice
- inhibitors of the transporter protein P-gp, such as clarithromycin
- Beta blockers add to the bradycardia (slow heartbeat) caused by digitoxin.
Drugs that can decrease the effectivity of digitoxin include:[3]
- substances that increase potassium levels, such as potassium sparing diuretics
- St John's Wort
- substances that bind digitoxin in the gut, such as aluminium containing antacids or colestyramine
Pharmacology
Mechanism of action
Digitoxin inhibits the
Pharmacokinetics
The drug is almost completely absorbed from the gut. When in the bloodstream, 90 to 97% are bound to
History
The first description of the use of
Use as a weapon
Marie Alexandrine Becker, a Belgian serial killer, was sentenced to death for poisoning eleven people with digitoxin.[citation needed]
In fiction
Digitoxin is used as a poison or murder weapon in:
- Agatha Christie's Appointment with Death
- Elizabeth Peters' Die For Love
- CSI, season 9, episode 19: "The Descent of Man"
- Rosewood season 2, episode 20: Calliphoridae and Country Roads
- "Casino Royale" (2006)
- "Uneasy Lies the Crown" on Columbo, season 9, episode 5 (1990)
- "Affair of the Heart" on McMillan and Wife, season 6, episode 5 (1977)
- Murder 101: "College can be a Murder"
- Several episodes of Murder She Wrote.
- Private Practice, season 4, episode 18: “The Hardest Part”
In The Decemberists's song, "The Rake's Song" on The Hazards of Love album, the narrator murders his daughter by feeding her foxglove.
Research
Digitoxin and related cardenolides display anticancer activity against a range of human cancer cell lines in vitro but the clinical use of digitoxin to treat cancer has been restricted by its narrow therapeutic index.[9][10] Digitoxin glycorandomization led to the discovery of novel digitoxigenin neoglycosides which displayed improved anticancer potency and reduced inotropic activity (the perceived mechanism of general toxicity).[11]
References
- PMID 11525233. Archived from the originalon 2013-01-05.
- ISBN 978-3-642-69046-4.
- ^ a b c d e f Haberfeld H, ed. (2021). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Digimerck 0,07 mg - Tabletten.
- S2CID 2324996.
- ^ "mediQ: Digitoxin". Retrieved 2021-09-14.
- ^ Withering W (1785). An Account of the Foxglove and Some of its Medical Uses: With Practical Remarks on Dropsy and other Diseases. Classics of Medicine Library.
- PMID 18127991.
- ISBN 978-0-471-89980-8.
- PMID 23525565.
- PMID 23210930.
- PMID 16105948.
Further reading
- 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. S2CID 19894541.
- 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. PMID 11515708.
- Haux J, Klepp O, Spigset O, Tretli S (2001). "Digitoxin medication and cancer; case control and internal dose-response studies". BMC Cancer. 1: 11. PMID 11532201.
- Srivastava M, Eidelman O, Zhang J, Paweletz C, Caohuy H, Yang Q, et al. (May 2004). "Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (20): 7693–8. PMID 15136726.
External links
Media related to Digitoxin at Wikimedia Commons
- Comparing the Toxicity of Digoxin and Digitoxin in a Geriatric Population: Should an Old Drug Be Rediscovered? on Medscape (registration required), a convenience link from the original. (subscription required)