Digitoxin

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Structural formula
Structure of digitoxin
General
Non-proprietary name Digitoxin
other names
  • Carditoxin
  • Digitophyllin
  • Digitrin
Molecular formula C 41 H 64 O 13
Brief description

small rectangular, bitter-tasting flakes

External identifiers / databases
CAS number 71-63-6
EC number 200-760-5
ECHA InfoCard 100,000,691
PubChem 441207
ChemSpider 389987
DrugBank DB01396
Wikidata Q423890
Drug information
ATC code
Drug class

Cardiac glycosides

properties
Molar mass 764.95 g · mol -1
Physical state

firmly

Melting point

256-257 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
06 - Toxic or very toxic 08 - Dangerous to health

danger

H and P phrases H: 301-331-373
P: 260-264-301 + 310 + 330-304 + 340 + 311-314-403 + 233
Toxicological data

0.18 mg kg −1 ( LD 50catoral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Digitoxin is a steroid - glycoside from the group of cardiac glycosides and is found in the leaves of the foxglove Digitalis purpurea .

Digitoxin consists of the aglycon digitoxigenin , which is linked to three sugar residues (digitoxose). Its effect is similar to digoxin from the foxglove Digitalis lanata , but due to the lack of an OH group, it has a longer half-life of 6-8 days and is mainly excreted via the liver.

history

The first use of thimbles was described in 1775. The first isolation took place in 1875 by Oswald Schmiedeberg . Further investigations followed by Claude-Adolphe Nativelle . The structure was partially cleared up in 1925 by Adolf Otto Reinhold Windaus and in 1962 completely.

Extraction

Digitoxin is obtained from the leaves of the red foxglove ( Digitalis purpurea ). Six grams of digitoxin can be isolated from ten kilograms of thimble leaves.

effect

Digitoxin has a positive inotropic effect on the heart muscles. By binding to the ryanodine receptor, digitoxin leads to an increase in the cytosolic calcium concentration, which improves the contractility of the heart muscle cells. Digitoxin use can cause anorexia , nausea , vomiting , diarrhea , confusion , visual disturbances, and cardiac arrhythmias . As with digoxin, poisoning with digitoxin can be treated with the anti-digoxin Fab fragment .

indication

Digitoxin is used for heart failure , especially with simultaneous kidney failure .

use

Digitoxin is not used as commonly for heart disease when compared to digoxin . Digitoxin and related cardenolides are being studied for the treatment of tumors . Digitoxin has a low therapeutic index . Furthermore, derivatives of digitoxin are being investigated.

Literary reception

Digitoxin is in the novel Appointment with Death by Agatha Christie used as a murder weapon. Furthermore comes digitoxin in Die For Love by Elizabeth Peters before, as well as in the TV series CSI: Vegas , Season 9, Episode 19: "The Descent of Man," in the television series Columbo , Season 9, Episode 5: "Uneasy Lies the Crown "(1990), in the TV series McMillan and Wife , Season 6, Episode 5:" Affair of the Heart "(1977), in Murder 101 :" College can be a Murder "and several times in the TV series Series murder is her hobby . In The Decemberists' song "The Rake's Song" , the narrator murders his daughter by feeding thimble .

Trade names

Monopreparations

Digimed (D), Digimerck (D, A)

Combination preparations

Augentonicum Stulln (CH)

Individual evidence

  1. a b c Entry on Digitoxin. In: Römpp Online . Georg Thieme Verlag, accessed on December 22, 2014.
  2. a b Entry on Digitoxin in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .
  3. Entry on Digitoxin in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  4. ^ Entry on Digitoxin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  5. ^ Withering, William: An Account of the Foxglove and Some of its Medical Uses: With Practical Remarks on Dropsy and other Diseases 1785.
  6. ^ WC Diefenbach, JK Meneely Jr: Digitoxin; a critical review . In: The Yale Journal of Biology and Medicine . 21, No. 5, 1949, pp. 421-431. PMID 18127991 . PMC 2598854 (free full text).
  7. Sneader, Walter: Drug discovery: A history in 2005, ISBN 978-0-471-89980-8 , S. 107th
  8. ^ GG Belz, K. Breithaupt-Grögler, U. Osowski: Treatment of congestive heart failure – current status of use of digitoxin. In: European journal of clinical investigation. Volume 31 Suppl 2, 2001, pp. 10-17, PMID 11525233 .
  9. ^ H. Fuerstenwerth: On the differences between ouabain and digitalis glycosides. In: American journal of therapeutics. Volume 21, number 1, 2014 Jan-Feb, pp. 35-42, doi : 10.1097 / MJT.0b013e318217a609 , PMID 21642827 .
  10. ^ Kurowski, V .; Iven, H .; Djonlagic, H .: Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies . In: Intensive Care Medicine . 18, No. 7, 1992, pp. 439-442. doi : 10.1007 / BF01694351 . PMID 1469187 .
  11. DM Roberts, NA Buckley: Antidotes for acute cardenolide (cardiac glycoside) poisoning. In: The Cochrane database of systematic reviews. Number 4, 2006, S. CD005490, doi : 10.1002 / 14651858.CD005490.pub2 , PMID 17054261 .
  12. Erland Erdmann: Therapy with cardiac glycosides. Springer-Verlag, 2013, ISBN 978-3-642-69046-4 , p. 43.
  13. L. Menger, E. Vacchelli, O. Kepp, A. Eggermont, E. Tartour, L. Zitvogel, G. Kroemer , L. Galluzzi: Trial watch: Cardiac glycosides and cancer therapy . In: Oncoimmunology . 2, No. 2, February 1, 2013, p. E23082. doi : 10.4161 / onci.23082 . PMID 23525565 .
  14. HA Elbaz, TA Stückle, W Tse, Y Rojanasakul, CZ Dinu: digitoxin and its analogs as novel cancer therapeutics . In: Experimental Hematology & Oncology . 1, No. 1, April 5, 2012, p. 4. doi : 10.1186 / 2162-3619-1-4 . PMID 23210930 .
  15. JM Langenhan, NR Peters, IA Guzei, FM Hoffmann, JS Thorson: Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization . In: Proceedings of the National Academy of Sciences . 102, No. 35, August 30, 2005, pp. 12305-10. doi : 10.1073 / pnas.0503270102 . PMID 16105948 .
  16. Red List online, as of September 2009.
  17. AM comp. d. Switzerland, as of September 2009.
  18. AGES-PharmMed, as of September 2009.