Digitoxin

Digitoxin

Systematic (IUPAC) name
(3β,5β)-3-[(O-2,6-dideoxy- β-D-ribo-hexapyranosyl-(1->4)- 2,6-dideoxy-β-D-ribo-hexopyranosyl)oxy]- 14-hydroxycard-20(22)-enolide
Clinical data
Trade names	Digitaline
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Bioavailability	95% (Oral)
Metabolism	Liver
Half-life	5~7 days
Identifiers
CAS number	71-63-6 Y
ATC code	C01AA04
PubChem	CID 441207
DrugBank	DB01396
ChemSpider	389987 N
UNII	E90NZP2L9U N
KEGG	D00297 N
ChEBI	CHEBI:28544 N
ChEMBL	CHEMBL254219 N
Chemical data
Formula	C41H64O13
Mol. mass	764.939 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C41H64O13/c1-20-36(46)29(42)16-34(49-20)53-38-22(3)51-35(18-31(38)44)54-37-21(2)50-33(17-30(37)43)52-25-8-11-39(4)24(15-25)6-7-28-27(39)9-12-40(5)26(10-13-41(28,40)47)23-14-32(45)48-19-23/h14,20-22,24-31,33-38,42-44,46-47H,6-13,15-19H2,1-5H3/t20-,21-,22-,24-,25+,26-,27+,28-,29+,30+,31+,33+,34+,35+,36-,37-,38-,39+,40-,41+/m1/s1 N Key:WDJUZGPOPHTGOT-XUDUSOBPSA-N N
N(what is this?)  (verify)

Digitoxin is a cardiac glycoside. It has similar 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, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current Western medical practice. While there have been several controlled trials which have shown digoxin to be effective in a proportion of patients treated for heart failure, there is not the same strong evidence base for digitoxin, although it is presumed to be similarly effective.^[1]

Toxicity

Digitoxin exhibits similar toxic effects to the more-commonly used digoxin, namely: anorexia, nausea, vomiting, diarrhea, confusion, visual disturbances, and cardiac arrhythmias. Anti-digoxin antibody fragments, the specific treatment for digoxin poisoning, are also effective in serious digitoxin toxicity.^[2]

History

The first description of the use of foxglove dates back to 1775.^[3] For quite some time the active compound was not isolated. It took until 1875 when Oswald Schmiedeberg was able to obtain a pure sample. The first structural analysis was done by Adolf Otto Reinhold Windaus in 1925 but the full structure with an exact determination of the sugar groups had to wait until 1962.^[4][5]

Use in fiction

Used as the murder weapon in Agatha Christie's Appointment with Death.

Used as a murder weapon in Elizabeth Peters' Die For Love.

Used as murder weapon with crop duster in CSI, Season 9 Episode 19: "The Descent of Man".

Digoxin used as a poison in "Uneasy Lies the Crown" Columbo 1990[Season 9, Episode 5]

Used as murder weapon in "Affair of the Heart" McMillan and Wife 1977 [Season 6, Episode 5].

Used as murder weapon in Murder 101: college can be a murder.

In the The Decemberists's song, "The Rake's Song" off of the The Hazards of Love album, the narrator murders his daughter by feeding her foxglove.

References

1. ^ Belz GG, Breithaupt-Grögler K, Osowski U (2001). "Treatment of congestive heart failure—current status of use of digitoxin". Eur. J. Clin. Invest. 31 (Suppl 2): 10–7. doi:10.1046/j.1365-2362.2001.0310s2010.x. PMID 11525233. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=2001&volume=31&issue=&spage=10. 
2. ^ Kurowski V, Iven H, Djonlagic H (1992). "Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies". Intensive Care Med 18 (7): 439–42. doi:10.1007/BF01694351. PMID 1469187. 
3. ^ Withering, William (1785). An account of the foxglove, and some of its medical uses: With practical remarks on dropsy and other diseases. http://books.google.com/books?id=tORsAAAAMAAJ. 
4. ^ . PMC 2598854. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2598854. 
5. ^ Sneader, Walter (2005). Drug discovery: A history. pp. 107. ISBN 9780471899808. http://books.google.com/books?id=mYQxRY9umjcC&pg=PA107. 

• Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P (2001). "Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells". Anticancer Drugs 12 (5): 475–83. doi:10.1097/00001813-200106000-00009. PMID 11395576. 
• Hippius M, Humaid B, Sicker T, Hoffmann A, Göttler M, Hasford J (2001). "Adverse drug reaction monitoring--digitoxin overdosage in the elderly". Int J Clin Pharmacol Ther 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. doi:10.1186/1471-2407-1-11. PMC 48150. PMID 11532201. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48150. 
• Srivastava M, Eidelman O, Zhang J, Paweletz C, Caohuy H, Yang Q, Jacobson K, Heldman E, Huang W, Jozwik C, Pollard B, Pollard H (2004). "Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells". Proc Natl Acad Sci USA 101 (20): 7693–8. doi:10.1073/pnas.0402030101. PMC 419668. PMID 15136726. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=419668. 

External links

• "Comparing the Toxicity of Digoxin and Digitoxin in a Geriatric Population: Should an Old Drug Be Rediscovered?"