1. What Role Does Digitalis Serve in Medicinal Cardiovascular Treatments? by Brennan Barkley

2. Overview “Digitalis” is often used to describe cardiac glycosides (Digoxin/Digitoxin) “Digitalis” is often used to describe cardiac glycosides (Digoxin/Digitoxin) Other active ingredients: Digitalin, Digitalein, Digitonin Other active ingredients: Digitalin, Digitalein, Digitonin These compounds are isolated from plants of the genus Digitalis or “Foxglove” These compounds are isolated from plants of the genus Digitalis or “Foxglove”

3. Structure Digoxin (C 41 H 64 O 14 )

4. Where Does it Come From? The extractions are taken from the leaves of the plant The extractions are taken from the leaves of the plant Only green, perfect leaves picked Only green, perfect leaves picked Unpleasant odor, bitter taste Unpleasant odor, bitter taste Digitalis purpurea

5. Early History The earliest use of cardiac glycosides dates back to the Roman Empire—red squill The earliest use of cardiac glycosides dates back to the Roman Empire—red squill William Withering, 1785—introduced Digitalis into medicine William Withering, 1785—introduced Digitalis into medicine Charles Darwin Charles Darwin

6. Modern Use Used to increase cardiac contractility Used to increase cardiac contractility (positive inotrope) (positive inotrope) Also used as an antiarrhythmic agent Also used as an antiarrhythmic agent

8. Mechanism?

9. Disadvantages Digitalis intoxication: Digitalis intoxication: Nausea Nausea Vomiting Vomiting Anorexia Anorexia Diarrhea Diarrhea Excessive amounts can lead to further heart problems—irregular pulse, convulsions Excessive amounts can lead to further heart problems—irregular pulse, convulsions Xanthopsia—Vincent Van Gogh Xanthopsia—Vincent Van Gogh

10. In the News In 2003, Charles Cullen admitted to killing nearly forty hospital patients with overdoses of compounds such as Digoxin In 2003, Charles Cullen admitted to killing nearly forty hospital patients with overdoses of compounds such as Digoxin

11. Research Lin H. Juang, Taiwan—prostate cancer Lin H. Juang, Taiwan—prostate cancer University of Sevilla, Department of Pharmacology, Spain—anti-tumor activity University of Sevilla, Department of Pharmacology, Spain—anti-tumor activity J. Haux Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim—anti- cancer research J. Haux Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim—anti- cancer research

12. Conclusions Glycosides isolated from the genus Digitalis have been used since the mid 18 th century to treat cardiac afflictions Glycosides isolated from the genus Digitalis have been used since the mid 18 th century to treat cardiac afflictions The extractions are taken from healthy leaves of the plant The extractions are taken from healthy leaves of the plant Mechanism of action—affects Na + /K + pump Mechanism of action—affects Na + /K + pump Excess amounts of the drug can have severe side effects or even be fatal Excess amounts of the drug can have severe side effects or even be fatal

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