Plants Used to Treat Heart Disease and Circulatory Problems - PowerPoint

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					Plants Used to Treat Heart Disease
    and Circulatory Problems
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
Cardiovascular disease

   Often thought to primarily affect men and older
   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
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
Living with cardiovascular disease

   The 61 million Americans with some form
    of cardiovascular disease include those
    –   high blood pressure
    –   coronary heart disease
    –   stroke
    –   congestive heart failure
    –   other conditions
Economic impact of cardiovascular

   Estimated cost of cardiovascular disease in the
    United States in 2001 was $298 billion,
    including health care expenditures and lost
   Costs will continues to grow as the population
Individual level risk factors for
cardiovascular disease

   High Blood Pressure
   High Blood Cholesterol
   Tobacco Use
   Physical inactivity
   Poor nutrition
   Obesity
   Diabetes
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
Short List of Plants Used in

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

   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
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
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
Digitalis purpurea

   Purple foxglove - an attractive biennial with
    large purple bell-shaped flowers in the
   Often used as a garden ornamental
   Leaves contain over 30 cardiac glycosides with
    digoxin and digitoxin the most significant
   Concentration of glycosides highest before
   Leaves dried, powdered, then extracted

Digitoxin and Digoxin

   Glycosides have similar action on the heart
   Follow somewhat different paths through the
   Have different levels of toxicity in the body

Sugars in digitalis glycosides

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

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
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

   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

   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%
Digitalis glycosides

   Indicated in cases of congestive heart failure
   Although some recent controversy as to
    whether it should be use in absence of atrial
Digitalis glycosides and blood

   Mixed data on effect of blood pressure
   Standard believe was that glycosides
    increased blood pressure
    –   Rise in Na and Ca contents of vascular smooth
    –   This induced vasoconstriction
   However recent studies showed patients with
    lower blood pressure – especially during night
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
Digoxin vs Digitoxin

   Digitoxin was standard until 1970s
   In 1970s serum drug assay became available
    for digoxin and oral prepartions became more
   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
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)

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

   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
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