Plants Used to Treat Heart Disease and Circulatory Problems

1. Plants Used to Treat Heart Disease and Circulatory Problems

2. Cardiovascular Disease • Heart disease and stroke are the principal components of cardiovascular disease • Heart disease and stroke are the first and third leading causes of death in the United States • Account for more than 40% of all deaths • About 950,000 Americans die of cardiovascular disease each year • One death every 33 seconds • 2,600 deaths each day

3. Cardiovascular disease • Often thought to primarily affect men and older people • However cardiovascular disease also a major killer of women and people in the prime of life • More than half of all cardiovascular disease deaths each year occur among women

4. Death rate only part of the problem • About 61 million Americans (almost one-fourth of the population) live with this disease • Heart disease is a leading cause of disability among working adults • Stroke alone accounts for disability among more than 1 million Americans • Almost 6 million hospitalizations each year are due to cardiovascular disease

5. Living with cardiovascular disease • The 61 million Americans with some form of cardiovascular disease include those with • high blood pressure • coronary heart disease • stroke • congestive heart failure • other conditions

6. Economic impact of cardiovascular disease • Estimated cost of cardiovascular disease in the United States in 2001 was $298 billion, including health care expenditures and lost productivity • Costs will continues to grow as the population ages

7. Individual level risk factors for cardiovascular disease • High Blood Pressure • High Blood Cholesterol • Tobacco Use • Physical inactivity • Poor nutrition • Obesity • Diabetes

8. High Cholesterol Profile • Percent of Americans ages 20-74 with high serum cholesterol: 19% • Mean serum cholesterol level, mg/dl: 203 • High serum cholesterol is most prevalent among white, non-Hispanic females • High serum cholesterol is least prevalent among Black males

9. Short List of Plants Used in Treatment • Aspirin • Digitoxin and digoxin • Statin drugs • Reserpine • Dietary remedies • Red wine • Garlic • Flavinoids, isoflavones • Monounsaturated fats

10. Aspirin • Suppresses prostaglandins by suppressing enzyme cyclooxygenase (COX) that leads to synthesis of prostaglandins • One of prostaglandins is thromboxane which is produced in platelets in blood • Aspirin halts thromboxane production - platelets become less sticky and less likely to plug up an artery - remarkably fast and can help survival during heart attack

11. Foxglove and heart disease • Foxglove - Digitalis purpurea • Extract called digitalis • Long history as a folk remedy for congestive heart failure (dropsy) • First mentioned in a 1542 Herbal • William Withering investigated this remedy from 1775-1785 - first scientific study of a medicinal plant

12. William Withering • In 1785 Withering published the result of his research in a monograph • An Account of the Foxglove, and Some of Its Medical Uses, with Practical Remarks on Dropsy, and Other Diseases • Careful descriptions of his experiments on dosage and the results

13. Digitalis purpurea • Purple foxglove - an attractive biennial with large purple bell-shaped flowers in the Scrophulariaceae • Often used as a garden ornamental • Leaves contain over 30 cardiac glycosides with digoxinand digitoxin the most significant • Concentration of glycosides highest before flowering • Leaves dried, powdered, then extracted

14. Foxglove Digitalis purpurea

15. Digitoxin and Digoxin • Glycosides have similar action on the heart • Follow somewhat different paths through the body • Have different levels of toxicity in the body

16. Digitoxin

17. Digoxin Sugars

18. Sugars in digitalis glycosides • 2 molecules of digitose • 1 molecule of 1-acetyl digitose • 1 molecule of glucose Digitose

19. Digitalis lanata • Although D. purpurea contains both digitoxin and digoxin, digitoxin levels are higher • Related species Digitalis lanata (wooly foxglove) is used for digoxin extraction • Both species are still used as sources of the glycosides

20. Physiological action • Both glycosides increase strength of the contractions in the heart • Prolongs relaxation period • Lowers heart rate • Effective treatment - not a cure • Fine line between a therapeutic and toxic dose of digitalis

21. Action • In medicinal doses, cardiac glycosides increase the contractions of heart and the force of the heart beat • Increases cardiac output - more blood pumped • Improved circulation, decreases edema, and increases kidney output • Most effective for congestive heart failure • Toxic doses cause arrhythmias or even cardiac arrest – fine line between medicinal and toxic

22. Action • Both glycosides inhibit Na/K dependent membrane ATPase in the myocardial cells • Intracellular Ca increase and conctractile response in augmented • Binding sites for digitalis glycosides on extracellular side of enzyme. • Therapeutic levels of digitalis inhibit 10 to 30% of enzyme - toxic levels inhibit 50%

23. Digitalis glycosides • Indicated in cases of congestive heart failure • Although some recent controversy as to whether it should be use in absence of atrial fibrillation

24. Digitalis glycosides and blood pressure • Mixed data on effect of blood pressure • Standard believe was that glycosides increased blood pressure • Rise in Na and Ca contents of vascular smooth muscle • This induced vasoconstriction • However recent studies showed patients with lower blood pressure – especially during night

25. Use in geriatric patients • About 13% of elderly use digitalis glycosides • Almost 20% of patients in nursing homes • Substantial risk of toxicity with 10 to 30% of hospitalized patients showing toxicity - and twofold increase in mortality • Risk of toxicity increases with age • 80% of toxicity cases over 60 yrs - have more risk factors - mortality as high as 58% with digoxin

26. Digoxin vs Digitoxin • Digitoxin was standard until 1970s • In 1970s serum drug assay became available for digoxin and oral prepartions became more standardized • Also digoxin has shorter half-life in body • These factors led physician to believe digoxin was safe • Digoxin one of most widely prescribed drugs today much more so than digitoxin

27. Differences in pharmacokinetics • Digitoxin is more completely and predictably absorbed from the gastrointestinal tract • Serum concentration not altered significantly by other medications or changes in renal or hepatic function • Digitoxin also has a much longer elimination time (half life 5 to 7 days as opposed to digoxin which is 1 to 2 days)

28. Digitoxin • Highly lipophilic • Extensively bound to plasma proteins • Mainly eliminated in urine and feces • Does not accumulate during kidney dysfunction • Bioavailabilty not reduced

29. Digoxin • Less lipophilic • Show lower protein binding • Shorter half-life • Mainly elimimiated by kidney • Accumulated quite rapidly in cases of insufficient kidney function • In patients with toxic side effects, 70% had renal insufficiency

30. Differences in toxicity • Prospective studies show • Digoxin toxicity rates 15 to 27% • Digitoxin toxicity rates 3 to 5.8% • Recent study in Florida showed odds of toxicity three times greater for patients taking digoxin as opposed to digitoxin