Plants Used to Treat Heart Disease and Circulatory Problems

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Plants Used to Treat Heart Disease and
Circulatory Problems
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Cardiovascular Disease

• What is cardiovascular disease?
• US statistics
• Cost of cardiovascular disease

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Common forms of cardiovascular disease

• The 61 million Americans with some form of
  cardiovascular disease including
• coronary heart disease
• stroke
• congestive heart failure
• high blood pressure
• other conditions

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Individual level risk factors for cardiovascular
disease

• High Blood Pressure
• High Blood Cholesterol
• Tobacco Use
• Physical inactivity
• Poor nutrition
• Obesity
• Diabetes

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Short list of plant-based compounds used in
treatment

• Aspirin
• Digitoxin and digoxin
• Statin drugs
• Reserpine
• Dietary remedies
• Red wine
• Garlic
• Flavinoids, isoflavones
• Monounsaturated fats

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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

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Foxglove and heart disease

• Foxglove - Digitalis purpurea
• Extract called digitalis
• Folk medicine
• William Withering investigated this remedy from
  1775-1785 - An Account of the Foxglove, and Some
  of Its Medical Uses, with Practical Remarks on
  Dropsy, and Other Diseases (1785)

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Foxglove Digitalis
purpurea
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Digitalis purpurea

• Biennial in the Scrophulariaceae
• Leaves contain over 30 cardiac glycosides with
  digoxin and digitoxin the most significant
• Concentration of glycosides highest before
  flowering
• Leaves dried, powdered, then extracted
• Digitoxin and Digoxin have similar action but
  slightly different pathways and toxicities

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Digitoxin
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Digoxin
Sugars
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Sugars in digitalis glycosides

• 2 molecules of digitose
• 1 molecule of 1-acetyl digitose
• 1 molecule of glucose

Digitose
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Digitalis purpurea and D. 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

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Mode of Action

• In medicinal doses, cardiac glycosides increase
  the strength of the contractions of heart and the
  force of the heart beat prolongs the relaxation
  period lowers the heart rate
• Increases cardiac output - more blood pumped
• Improved circulation, decreases edema, and
  increases kidney output
• Most effective treatment for congestive heart
  failure NOT A CURE
• Toxic doses cause arrhythmias or even cardiac
  arrest fine line between therapeutic and toxic
  dose

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Action

• Both glycosides inhibit Na/K dependent membrane
  ATPase in the myocardial cells
• Intracellular Ca increase and contractile
  response is 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

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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

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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

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Digoxin vs Digitoxin

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

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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)

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Digitoxin

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

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Digoxin

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

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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

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Mortality rate at various serum digoxin
concentrations