Transcript Variations in response to drug therapy

Genetic, Psychosocial, and Cultural Influences
Assessing for variations in response
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Health perception-health management
Nutritional-metabolic
Elimination
Activity-exercise
Cognitive-perceptual
Sleep-rest
Self-perception
Role-relationship
Sexuality-reproductive
Coping-stress tolerance
Value-belief
 Health perception – health management
 Attitudes toward health (compliance)
 Alcohol, drugs / tobacco
 Access to care, insurance
 Use of alternative therapies (cultural, spiritual)
 Explanatory models of illness / goals of treatment
 Nutritional – metabolic
 Genetic differences in metabolism
 Fat to muscle ratio (age, gender)
 Food-drug interactions
 Elimination
 Renal and hepatic function
 Cognitive – perceptual
 Ability to understand
 Visual acuity
Genetic variations
 INH
 Toxic in certain Caucasian Americans (slow
metabolizers)
 Beta-blockers
 Ineffective in some African Americans
 Codeine
 Ineffective in some Asian Americans (not converted to
morphine)
 Coumadin
 Toxic in certain Asian and African Americans
Things to watch for
Pharmacogenetics
 Individual variation in response to drug therapy.
 This variation is related to genetic alterations known
as polymorphisms.
 Some pharmacogenetic differences are inherited along
ethnic or racial lines.
 Other differences are unique to people and not
inherited.
 Genotype testing is now available for some CYP450
enzymes.
Pharmacogenetics
 But genetics isn’t the only factor. In a United
Kingdom study with DMARDs (disease-modifying
anti-rheumatic drugs) in Southeast Asian
immigrants, they were found to discontinue the
drugs more often than Northern Europeans.
 Communication and cultural differences in
response to chronic disease may be as important as
genetic response to the drugs. Reference:
http://rheumatology.oxfordjournals.org/cgi/conte
nt/full/42/10/1197
Ethnopharmacology
 Another name for another way to examine differences
in response to drug therapy.
 The difficulty lies in identifying the genetic, cultural,
racial and ethnic factors behind variations in response.
 “Historically, most drug trials have been conducted
using white men; the results have then been
generalized to all patients receiving the drugs studied.”
 http://employment.thresholds.org/pdf/Munoz_Hilgen
berg_Paper.pdf
An example: placebo effect
 In a British study, 835 women who regularly used analgesics
for headache were randomly assigned to one of four groups
(43). One group received aspirin labeled with a widely
advertised brand name. The other groups received the
same aspirin in a plain package, placebo marked with the
same widely advertised brand name, or unmarked placebo.
 Branded aspirin worked better than unbranded aspirin,
which worked better than branded placebo, which worked
better than unbranded placebo.
 http://www.annals.org/cgi/content/full/136/6/471
Interesting example….
 The beta-blocker propranolol is more effective in reducing
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blood pressure and heart rate in Chinese than in Whites.
Paradoxically, the Chinese subjects metabolized
propranolol much more rapidly than the White subjects
Pharmacokinetic properties, therefore, do not explain the
increased sensitivity of the Chinese
The mechanism for the increased sensitivity is not clearly
determined, but could be because of a greater suppression
of renin in the Chinese population
http://cobb.nmanet.org/images/uploads/Racial_and_Ethni
c_Differences_in_Response_to_Medicine.pdf p.18
Another example…..
 There are general differences in the pathophysiology of
hypertension between Black and White populations.
 Black hypertensives exhibit enhanced sodium
retention, a higher incidence of salt-sensitive
hypertension, expanded blood volume, more frequent
proteinuria, and a higher prevalence of low blood
renin activity
 These factors may underlie some of the observed
differences in the effectiveness of various
antihypertensive drugs in Black populations. p.18
But what about culture?
 The spirit catches you and you fall down: a Hmong
child, her American doctors and the collision of two
cultures by Anne Fadiman (1997)
 http://en.wikipedia.org/wiki/The_Spirit_Catches_You
_and_You_Fall_Down
Another culture….
 Barefoot doctors of China
 Their purpose was to bring health care to rural areas
where urban-trained doctors would not settle.
 They promoted basic hygiene, preventive health care,
and family planning and treated common illnesses
 Mao Zedong’s famous healthcare speech in 1965
institutionalized these rural healthcare workers.
 http://en.wikipedia.org/wiki/Barefoot_doctor
What about other cultures?
 America is a “melting pot” of cultures, yet…
 Often these cultures don’t “blend” but rather retain
some elements of their differences.
 But what is a culture? Is there Hispanic culture?
 Are Africans the same as African-Americans? Are their
similarities and differences the result of genetics? Or
culture? Or both?
 Questions? Comments?