Cultural and Genetic Diversity

in America:
The Need for Individualized
Pharmaceutical Treatment

by
Valentine J. Burroughs, MD
Chair, Health Policy Committee
Board of Trustees
National Medical Association

Randall W. Maxey, MD, PhD

Chairman, Board of Trustees
National Medical Association

Lavera M. Crawley, MD
Advisory Board, Division of
Biomedical Education and Research
National Medical Association

Richard A. Levy, PhD

Vice President, Scientific Affairs
National Pharmaceutical Council
About the Authors
Valentine J. Burroughs, MD, is Chair of the Health Policy Committee for the National Medical
Association Board of Trustees. Dr. Burroughs is a practicing Board Certified endocrinologist and
internist in New York City. He is Medical Director of Health Care New York IPA, Associate Medical
Director at Group Health Insurance of New York, and Associate Medical Director and Chairman of
Medicine at North General Hospital in Manhattan.

Randall W. Maxey, MD, PhD, is Chairman of the National Medical Association Board of Trustees
and past President of the Golden State Medical Association and the Charles R. Drew Medical
Society. He has practiced nephrology in the Los Angeles area for over 24 years and holds staff
appointments at various hospitals. He has conducted research in cardiovascular pharmacology and
hypertension. Dr. Maxey has established several dialysis centers in California, the South Pacific and
in Africa.

Lavera M. Crawley, MD, is a member of the Advisory Board for the National Medical Association
Division of Biomedical Research and Education. She also serves as the Executive Director for the
Initiative to Improve Palliative Care for African Americans, as well as a researcher and Lecturer in
Medicine at the Stanford University Center for Biomedical Ethics. Dr. Crawley’s publications focus
on issues of cultural diversity in serious illnesses, and in race/ethnicity and trust in doctor-patient
relationships.

Richard A. Levy, PhD, is Vice President for Scientific Affairs at the National Pharmaceutical Council
(NPC). Dr. Levy has spent over thirty years teaching, writing, and conducting research in universities
and private industry. His current interests include tracking, analyzing, and communicating trends
affecting pharmaceutical innovation; and developing information on management of medications by
individuals and organizations. Before coming to NPC, he taught and conducted research in
neuropharmacology at the University of Illinois College of Medicine.

About the National Medical Association (www.nmanet.org)

The National Medical Association (NMA) is the collective voice of African American physicians
and the leading force for parity and justice in medicine and the elimination of disparities in health.
The National Medical Association is a 501(c)(3) national professional and scientific organization
representing the interests of more than 25,000 physicians and their patients. Established in 1895,
NMA is committed to 1) preventing the diseases, disabilities and adverse health conditions that
disproportionately or differentially impact African American and underserved populations,
2) supporting efforts that improve the quality and availability of health care to poor and underserved
populations, and 3) increasing the representation and contribution of African Americans in medicine.

About the National Pharmaceutical Council (www.npcnow.org)

Since 1953, the National Pharmaceutical Council (NPC) has sponsored and conducted scientific,
evidence-based analyses of the appropriate use of pharmaceuticals and the clinical and economic
value of pharmaceutical innovations. NPC provides educational resources to a variety of health care
stakeholders, including patients, clinicians, payers and policy makers. More than 20 research-based
pharmaceutical companies are members of the NPC.

© November, 2002. National Pharmaceutical Council and National Medical Association

TABLE OF CONTENTS

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Toward Individualized Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Purposes of This Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
Disparities in Health Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8
Disparities in Cultural Competency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Disparities in Health Literacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Interplay of Environmental, Genetic, and Cultural Factors . . . . . . . . . . . . . . . . . . . . . . . . . . .12
Environmental Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12
Genetic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
Clinical relevance of genetic differences (polymorphisms) . . . . . . . . . . . . . . . . . . . . . .14
Racial differences in response to medication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
Cultural Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17
Trust and respect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17
Health beliefs and practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18
Family values . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20
Effect of cultural factors on medication compliance . . . . . . . . . . . . . . . . . . . . . . . . . . .21
The Future of Individualized Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22
Conclusions and Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

1
 EXECUTIVE SUMMARY

It is now well documented that substantial disparities exist in the quality and quantity of medical
care received by minority Americans, especially those of African, Asian, and Hispanic heritage.
Pharmacogenetic research in the past few decades has uncovered significant differences among
population groups in the metabolism, clinical effectiveness, and side effect profiles of many clinically
important drugs. In addition, differences in how various populations view and respond to medicines
underscores the need for an individualized approach to pharmaceutical therapy. Historically, the
special needs and responses to pharmaceutical treatment of these groups have been undervalued
or ignored. All of these differences must be taken into account in the design of cost management
policies such as formulary management, therapeutic drug substitution, and step-care protocols.
These programs should be broad and flexible enough to enable rational choices and individualized
treatment for all patients, regardless of racial or ethnic origin.

This report reviews the environmental, genetic
and cultural factors that underlie variations in
drug response among different population
groups. Population groups that have been
conventionally defined along racial and ethnic
categories comprise important subgroups whose
special needs and drug responses traditionally
have been undervalued or ignored. Given the
genetic and cultural variation among individuals
in these groups, drug
management policies in both
Genetic research in public and private pay
the past few decades pharmaceutical programs must
be flexible enough to
has uncovered accommodate patients’ specific
significant differences needs.
among racial and The factors determining
ethnic groups in the population variations in response
to medications are complex and
metabolism, clinical interdependent. Environmental
effectiveness, and factors (e.g., climate, smoking,
alcohol consumption) may have a
side effect profiles of profound effect on drug
therapeutically metabolism. Biologic factors such
as genetic polymorphisms
important drugs. (naturally occurring variations in
the structures of genes, drug
metabolism enzymes, receptor proteins, and
other proteins involved in drug response or
disease progression), age, and gender have
significant influence and may require the use of
alternate drugs or dosages in patients of
different racial and ethnic backgrounds. Genetic
research in the past few decades has uncovered
significant differences among populations in the
metabolism, clinical effectiveness, and side
effect profiles of therapeutically important
drugs; however, most of the research applies to
African Americans, Asians, and Caucasians.
Fewer studies have specifically targeted
Hispanics who, according to the 2000 U.S.
Census, represent the second-largest
ethnocultural group.
Cultural or psychosocial factors have been
documented to affect a patient’s adherence to,
and therefore the effectiveness of, drug therapy.
For example, trust and respect for patients and
their health beliefs and practices, as well as
communications issues, have been found to
influence adherence to medication regimens.
Patients’ beliefs about the nature of disease,
acceptance of side effects, and preferences
regarding herbal or traditional therapies may be
influenced by a range of sociocultural
influences, including gender, socioeconomic
class, education, immigrant status, and religion,
all of which must be taken into account.
Additionally, communications barriers may lead
to incorrect interpretations of diagnoses and
instructions regarding treatment. A frequently
overlooked and underemphasized barrier,
especially in the elderly and in underrepresented
minorities, is inadequate health literacy. This
comprises their ability to understand and follow
through on health information matters. Of
greater significance is the recognition of the
considerable skills that these patients have in
concealing their poor health literacy. Taken
together, these variables dictate that in order to
be effective, therapy must be individualized.

2
Recommendations
Health care policy makers and providers should
pay attention to the need to individualize drug
therapy for specific population groups. The
following recommendations could benefit the
quality of care for racial and ethnic
subpopulations and may also help to control
health care costs.
1. Health care institutions should implement
cost containment practices that are broad and
flexible enough to enable rational choices of
drugs and formulations for all patients,
regardless of race or ethnic origin.
2. Physicians should give individualized
treatment to each patient and prescribe drug
therapy that takes into account racial or
ethnic origin and sociocultural influences.
Physicians should also be alert to atypical
drug responses or unexpected side effects
(especially with cardiovascular or psychotropic
agents) when they treat patients from diverse
racial and ethnic backgrounds. Patients may
not be taking the medication properly due to
misunderstood instructions, or
misperceptions about Western medicine or
the severity of the disease. Dosage
adjustments may be required in some
patients if supported by pharmacological
evidence.
3. Pharmaceutical companies should continue to
include significant numbers of patients
representing varied racial and ethnic groups in
drug metabolism studies and clinical trials.
Most companies test and evaluate new
pharmacological compounds on numerous
population subgroups. Inclusion of different
racial and ethnic populations in clinical trials is
likely to reveal drug actions and side effects
specific to these groups, and may also to lead
to the discovery of therapies of specific
advantage to patients of varied racial and
ethnic backgrounds.
4. Hospitals, managed care groups, and other
providers of health care services should
endeavor to employ practitioners who are
racially and ethnically representative of the
patient population being served. Provider
organizations should develop and institute
specific training in cultural competence for all
practitioners who have direct patient
contact–especially physicians, pharmacists,
nurses, and physician assistants.
Toward Individualized Therapy
Race and ethnicity have been used as factors in
determining if an individual
will respond in the
expected way to a given
drug therapy. However,
Racial and ethnic
race is an imprecise groups comprise
substitute for genetic
variations that an individual
important
may or may not possess. subpopulations whose
Technological advances in
the wake of the Human
special needs and drug
Genome Project will responses traditionally
eventually enable us to
move beyond flawed
have been undervalued
concepts of race and to or ignored.
tailor drug therapy
precisely to each patient. It
is now possible to take a genetic “fingerprint”
of an individual and precisely determine the
presence of polymorphisms in the genes known
to be involved in drug interaction. Instead of a
person’s racial category being a risk factor for
the possession of polymorphisms involved in
drug response, a genotypic profile can
determine with certainty whether or not the
individual possesses these polymorphisms.
In the future, drug treatment will be individually
tailored rather than race-based. Genetic
fingerprinting using DNA arrays is already
practical, but the knowledge base relating
genomic variations to drug response and disease
progression has not been developed. Studies in
which DNA fingerprints are correlated with data
present in medical records about medical history
and drug response will have a profound impact
on the ways in which new drugs are developed
and used.
3
 However, treating individuals involves more than
awareness of genetic variations. Apart from the
physiological complexities associated with
appropriate prescribing for different racial and
ethnic groups, practitioners face the added
challenge of delivering effective pharmaceutical
care to people within a psychosocial context
appropriate to their culture and level of health
literacy. The great diversity in our patient
population demands a framework in which the
practitioner can approach all patients, regardless
of racial, ethnic, or sociocultural background, as
egalitarian partners in care.
4
Although any discussion of sociocultural
competence can list examples of our
differences, it is important to remember the
many similarities exist among diverse peoples.
All patients seeking care have recognized a
need for that care. All share feelings of need,
fear, mistrust, lack of control, hope, and
disconnection from their normal world of health.
When these feelings are acknowledged and
respected by a culturally competent practitioner,
partnerships can be built in which any cultural
health belief or treatment preference can be
discussed.
INTRODUCTION
Individual genetic polymorphisms are naturally
occurring variants in the structures of genes,
drug metabolism enzymes, receptor proteins,
and other proteins involved in drug response or
disease progression. These polymorphisms
change gradually in prevalence across
continents and do not separate populations into
clearly demarcated groups that correspond to
popular ideas of race.
The most obvious manifestations of racial
differences – skin color, cranial features, etc. – are
superficial characteristics that have little relevance
to drug responses or to the progression of
complex diseases such as diabetes mellitus,
coronary heart disease, etc.1,2 It should be
emphasized that humans are one species.
Although we have evolved as geographically
separated groups, our differences have not yielded
large variations in genetic composition. Those
genetic differences that do exist reflect variations
from only a small number of genes. Therefore,
“race” is an imprecise substitute measure of
genetic differences among populations.
The idea of race is extremely complex. It refers
to a grouping of humans into specific categories
that have no underlying biological underpinning.
Yet, because the groupings are largely based on
physically visible features, race appears to be
real. This may explain why race as a flawed
concept is difficult to eradicate from usage – in
both scientific and general discourse. For
example, skin pigmentation has been used as a
marker for race (white, black, red, yellow). But
skin color alone is quite deceptive, as the same
range of colorations can be found among
persons from different population groups. For
example, those from certain Asian backgrounds
can be as dark as those from Africa. And those
from African ancestries can be as light as those
whose ancestry can be traced to Europe.3
Historically, the categorization of human beings
according to physical attributes linked to
geography and later termed race can be traced
back to the eighteenth century.3,4,5 Not only were
varieties of humans described, but also a
hierarchical ordering was ascribed to these
varieties, where one group (those who could
later be called “white”) was considered the
most superior. Therefore, embedded in the idea
of race is this notion of the ascendancy of some
groups over others.
In the U.S., criteria used to identify “racialized”
groups have not been based solely on biological
markers, but also on the idea of ethnic or
cultural indicators. For example, Hispanics
comprise a group of individuals who generally
share a linguistic heritage but who represent
multiple nationalities and racialized groupings,
including white, black and indigenous Indians.
The terms ethnicity and culture have also been
subject to conceptual misunderstanding and
thus require more precise and coherent
definitions if they are to be useful. Together they
refer to combinations of “socioeconomic,
religious, and political qualities of human
groups, including language, diet, dress,
customs, kinship systems, and historical or
territorial identity.”6
Like “race”, both ethnicity and culture are also
subject to social constructions whose
borderlines are
not easily
mapped.7,8 They
In addition to the physiological
reflect our own complexities associated with
projections and
are also subject
appropriate prescribing for different
to individual racial and ethnic groups,
fluidity. One can
inhabit multiple
practitioners face the added
cultural or ethnic challenge of delivering effective
identities and
move between
pharmaceutical care to these
them depending individuals within a psychosocial
on need or
circumstance.
context appropriate to their culture.
Thus, we must
resist any temptation to view these concepts as
having material reality. The conditions and ways
certain individuals or groups can be assigned to
a specific ethnic or cultural group must be
specified. For example, we should speak not of
Hispanic culture but rather of cultural beliefs
held by certain populations of persons from
specific areas, say Puerto Rico or El Salvador.
5
 Research in the last 35 years has uncovered
varying distributions of genetic polymorphisms
in enzymes and receptors associated with drug
metabolism. These are reflected in differences
among population groups in clinical responses
to drugs and in drug side effects. For example,
black and white patients have been shown to
differ significantly in their responses to beta-
blockers, angiotensin-converting enzyme (ACE)
inhibitors, and diuretics used either alone or in
combination for the treatment of high blood
pressure. Some populations of Chinese are
considerably more sensitive than whites to the
effects of the beta-blocker propranolol on heart
rate and blood pressure. African Americans and
Chinese Americans metabolize nicotine more
slowly than do whites, and genetic variations
associated with slower nicotine metabolism are
more common in some Asian populations.9,10,11
As compared to some whites, certain Asian
groups are more likely to require lower dosages
of a variety of different drugs used to treat
mental illness, including lithium,
antidepressants, and antipsychotics.
Concepts of identity based on racial markers,
ethnicity or culture may be useful when
discussing trends among populations, but they
cannot predict individual behavior. We cannot
rely on a form of racial profiling – using visible or
socially constructed markers, such as skin
pigmentation, eye-shape, language use, or
health beliefs, to accurately identify the
presence or absence of polymorphisms in drug-
metabolizing enzymes or drug receptors.2,12
6
The usefulness of these concepts lies in their
ability to increase the clinician’s awareness of
differences and the threshold for considering
alternative treatment modalities, but not for
limiting options in diagnosis or treatment for an
individual patient. To do otherwise would be to
stereotype in ways that could, in turn,
contribute to the inequities reflected in health
disparities. In addition to the physiological
complexities associated with appropriate
prescribing for different racial and ethnic
groups, practitioners face the added challenge
of delivering effective pharmaceutical care to
these individuals within a psychosocial context
appropriate to their cultural beliefs and
practices. The great diversity in our patient
population demands a framework in which the
practitioner can approach all patients as
egalitarian partners in care, regardless of
cultural background.
Although any discussion of sociocultural
competence can list examples of our
differences, it is important to remember the
many similarities among diverse peoples. All
patients seeking care have recognized a need
for that care. All share feelings of need, fear,
mistrust, lack of control, hope, and
disconnection from their normal worlds of
health. When these feelings are acknowledged
and respected by a culturally competent
practitioner, partnerships can be built in which
any cultural health belief or treatment
preference can be discussed.
Purposes of This Report
This report 1) reviews the interrelated causes of
variability in response to medicines among racial
and ethnic groups; 2) discusses examples of
drugs to which racial and ethnic groups respond
differently; 3) discusses the implication for
pharmaceutical cost containment practices; and
4) makes recommendations for health care
providers and policy makers who are
responsible for clinical decisions affecting
patient care.

Terms Used in This Report:

• Ethnicity and Culture – Refer to combinations of socioeconomic, religious, and political qualities
of human groups, including language, diet, dress, religions, customs, beliefs, worldviews,
kinship systems, and historical or territorial identity.

• Extensive Metabolizer – An individual who metabolizes a drug at a normal rate of efficiency.

• Health Literacy – The ability of an individual to understand and follow through on health
information matters.

• Pharmacodynamic Properties – Effect of a drug on the body.

• Pharmacogenetics – The study of variations in a gene on drug response.

• Pharmacogenomics – The study of variations in multiple genes on drug response.

• Pharmacokinetic Properties – Absorption, distribution, metabolism, excretion of a drug.

• Polymorphisms – Naturally occurring variations in the structures of genes, drug metabolism

enzymes, receptor proteins, and other proteins involved in drug response or disease
progression.

• Poor Metabolizer – An individual who does not metabolize a drug efficiently.

• Racial Group – A group of people who share socially constructed differences based on visible
characteristics or regional linkages.

7
 DISPARITIES IN HEALTH CARE
Disparities in the quality of medical care
provided to patients representing different racial
and ethnic groups have been extensively
documented.13 The recent report of the Institute
of Medicine (IOM), "Unequal Treatment:
Confronting Racial and Ethnic Disparities in
Healthcare," illustrates in detail that racial and
ethnic disparities in health care do exist and are
prevalent in both the treatment of medical
illness and in the delivery of health care
services to minorities in the U.S.14
Of greater significance is the finding that these
disparities still exist even after adjustment for
differences in socioeconomic status, insurance
coverage, income, age, co-morbid conditions,
The recent report of the Institute of Medicine
(IOM), "Unequal Treatment: Confronting Racial
and Ethnic Disparities in Healthcare," illustrates
in detail that racial and ethnic disparities in
health care do exist and are prevalent in both
the treatment of medical illness and in the
delivery of health care services to minorities in
the United States.
Figure 1. Diversity of the U.S. Population
Black or African
Hispanic American
Two or more races
White
Source: Bureau of Census data for 2000.
8
expression of symptoms, and access-related
factors. These disparities are not confined to any
one aspect of health care, and can also be
found in the delivery of pharmaceutical services.
Most studies have focused on African
Americans, but other studies have shown that
Hispanic and Asian Americans are similarly
affected. Patients in these groups receive less
intensive medical treatment than the nation as a
whole, including fewer vaccinations, less drug
therapy for pain, fewer antiretroviral drugs for
HIV/AIDS, and fewer antidepressants.15,16,17,18,19,20
Low-income Hispanic children with asthma were
less likely than their white and African American
counterparts to have taken inhaled beta-agonist
or anti-inflammatory medications before
hospitalization.21
African American and Hispanic patients with
severe pain are less likely than white patients to
be able to obtain commonly prescribed pain
medicines, because pharmacies in
predominantly non-white communities do not
carry adequate stocks of opiates.22 Other studies
have revealed undertreatment of Hispanics and
African Americans for pain from fractures,
inadequate management of postoperative pain
in non-white patients, and a lower likelihood of
curative surgery for cancer
in African Americans than
in whites of equivalent
socioeconomic status.20
Disparities in the quantity
and quality of care
received can stem from a
variety of causes. There
Asian are often communication
obstacles between a
American Indian and patient and provider that
Alaska Native can be due to language, a
Native Hawaiian and difference in cultural
Other Pacific Islander background, preconceived
Other stereotypes, or incorrect
assumptions about what
the patient does and does
not understand about
their health. This can lead
to noncompliance with
prescribed treatments and
ineffective management
of disease.
The demographic changes anticipated over the intended to serve. These groups may be further
next decade magnify the importance of these disadvantaged if they do not have access to
disparities. According to the 2000 census, racial individualized care with appropriate
and ethnic groups other than “white” make up pharmaceuticals.
almost one third of the U.S. population (Figure
1). African Americans and Hispanics represent a
growing percentage of the urban population in
the U.S. These groups constitute the new urban
majority in cities such as Washington, Detroit,
and Los Angeles.

A disproportionate fraction of these urban

Americans depend on Medicare or Medicaid as
their sole health care payer. As drug coverage
policies within these programs evolve, they
must account for the special needs of a growing
percentage of the patient groups they are

Common Cultural Themes and Health Beliefs of the Dominant Society in the U.S.
Although not universal, there are some common themes and health beliefs of the dominant
society in this country. These broad concepts are only crude indicators and certainly do not
characterize the thinking of all Americans. On the other hand, neither are they necessarily held
only by the non-Hispanic white majority. The authority of the dominant society has been
internalized by many groups. In addition to ethnic and cultural differences, generational and
gender factors are also likely to be important determinants of health beliefs for Americans. Some
common themes include:23

• A relative intolerance of pain. Unlike many other culturally held beliefs, where pain is seen as
part of life, the typical Western attitude toward pain is to relieve it as soon as possible.

• A high expectation that one’s disease can and will be cured or at least “managed.”

• The need to leave the doctor’s office with a prescription.

• The belief that medications should be powerful but free of risk, and that strong medications
should be available only by prescription.

• A belief in the magic of high technology and one’s entitlement to it.

• The belief that management of microbes is more important than bolstering resistance to them.

• The belief that the physical aspects of disease are separate from its emotional and
spiritual dimensions.

• The belief that the body is a machine and that proper maintenance (diet, exercise) will prolong
its useful life; and that technology enables replacement of defective or worn out parts.

• A belief in the sanctity of the doctor-patient relationship and the right to individualized treatment.

• A belief that mental diseases are not as important, or as “real” as somatic diseases.

9
 Disparities in Cultural Competency
At the most basic level, care may be
compromised due to cross-cultural language and
other communication barriers. For instance,
among adult Hispanics with asthma who spoke
only Spanish, there was a greater likelihood of
missed follow-up appointments, non-adherence
to medications, and emergency room visits
among those whose physician spoke only English
compared to those with bilingual physicians.24
Culturally shaped beliefs play a vital role in
determining whether an explanation of illness or
treatment makes sense. Indigenous systems of
health beliefs, practices and medicines exist in
all societies and exert profound influence on
patients’ attitudes and behaviors.25,26 Since
cultural beliefs may greatly influence treatment
outcomes, it is important to assess the
likelihood that a patient will act on these beliefs.
One strategy for improving cultural competence
among health care providers is for health care
providers themselves to better reflect the
diversity of those they serve. One in four
Americans is non-white, Hispanic, or Native
American, but fewer than 10 percent of those in
the health professions workforce represent these
minority groups.27 African American and Hispanic
physicians make up only 2.2 percent and 2.8
percent of all practicing physicians in America
respectively, a woefully inadequate number to
care for these groups, each of which exceeds
10 percent of the population. Health care provider
organizations that effectively close this gap will
achieve a competitive advantage in serving the
needs of their ethnically diverse customers.
While ideally patients would be matched with
providers of similar backgrounds, realistically we
must find ways to train all health care providers
to be sensitive to the sociocultural beliefs that
may influence the effectiveness of any
prescribed treatment regimen. A mismatch
between lay and
professional perspectives
often results in patients’
dissatisfaction with
One in four Americans is non-white, Hispanic, or
treatment.28,29,30 Native American, but fewer than 10 percent of
those in the health professions workforce
represent these minority groups.
10
Disparities in Health Literacy
Health literacy refers to the set of skills needed
to read, understand, and act on basic health
care information. Over 90 million adults in the
U.S. have low health literacy skills, with limited
ability to read and understand the instructions
contained on prescriptions or medicine bottles,
appointment slips, informed consent
documents, insurance forms, and health
educational materials.31
Members of socioculturally disadvantaged
groups, especially those for whom English is a
second language, are more likely than educated
or socioeconomically advantaged adults to have
limited literacy skills, thus impacting their ability
to understand and follow prescribed health care
regimens.31,32 There is a relationship between low
literacy and self-management skills, including the
ability to take medications properly. For example,
asthma patients with lower literacy levels were
found to have a relatively poorer technique when
using their metered-dose inhaler.33
In another case, many patients receiving acute
care at two urban hospitals were unable to read
and understand basic medical instructions.34
Forty-two percent did not understand directions
for taking medication on an empty stomach, and
twenty-six percent did not understand information
on scheduling their next appointment. Thirty-five
percent of the English-speaking patients had
inadequate or marginal functional literacy, but for
the Spanish-speaking patients, the figure was
even higher (62 percent).
For some serious chronic diseases, such as
diabetes, low health literacy poses a
compounded threat to overall health. Because
self-management relies heavily on printed
instructions, literacy is a key factor. A study of
low-income African American patients with non-
insulin-dependent diabetes found the functional
health literacy level was adequate in only 25 to
47 percent of patients at diabetes clinics.35
Another study found that patients with
inadequate health literacy were more likely to
have poor control of their blood sugar levels and
to report eye problems (usually involving blood
vessels of the retina) which may progress to
blindness.36
materials designed for them were written at a
10th grade reading level.38 In another example,
less than half of the cancer education materials
specifically targeting African Americans reflected
the cultural values of African Americans, and few
were written at a reading grade level for those
with low literacy skills.39

Furthermore, low-literacy patients did not readily
identify themselves; 43 percent of those with
low health literacy denied having any difficulty in
reading; 54 percent of those with low-literacy
said they did not usually ask anyone to help
them read medical forms, and only 29 percent
reported asking someone (usually relatives or
neighbors) to help them read the written
materials given to them. Such patients were
least likely to ask their physician for help.35
Standard patient informational practices have
been shown to be insufficient to overcome the
barriers posed by low health literacy.37 Often,
health educational materials are written at an
inappropriate reading level, especially for minority
groups in which English may be a secondary
language. For example, in one study, although
many American Indian diabetic patients scored at
a 5th grade reading level, the diabetes education
Although much effort has been devoted to
improving the quality of written information,
improvement in oral and visual communication
to convey necessary medical information has
received inadequate attention.37 Health care
practitioners are therefore challenged to
communicate clearly and concisely with
patients and to take a patient-focused approach
to care. This also involves perceiving and
surmounting less visible barriers such as
patient confidence, shame, or fear. Practitioners
must be able to communicate effectively across
cultural, socio-economic, educational, and
geographical differences.
Practitioners must be able to communicate
effectively across cultural, socio-economic,
educational, and geographical differences.

The Language of Medicine

Due to the highly technical nature of the language of medicine, patients may not understand
seemingly common medical terms. Compounding the problem is the skill of patients in
concealing their poor health literacy. They usually will not acknowledge their deficiency due to
feelings of shame, even though it interferes with their health.40

In a study of health vocabulary, only 13 percent of participants understood the meaning of the word
“terminal,” only 18 percent understood “malignant,” and only 35 percent understood “orally.”41

In a study of Medicare patients, striking deficiencies were found in their understanding of

critical areas of health care:42

• 48 percent did not understand written instructions to “take medicine every six hours.”
• 68 percent could not interpret a blood sugar level.
• 27 percent did not understand “take medicine on an empty stomach.”
• 27 percent could not identify their next appointment.
• 100 percent could not understand a statement of Medicaid rights written at a 10th grade
reading level.

11
 INTERPLAY OF ENVIRONMENTAL, GENETIC,
CULTURAL FACTORS
Figure 2. Factors Contributing to Variability in Drug Response
Adapted from Poolsup et al43
The factors contributing to variability in drug
response are complex and interrelated (Figure
2). Differences in drug response among racial
and ethnic groups are determined by
environmental, genetic and cultural (in this
context, psychosocial) factors. These factors
may operate independently or they may interact
dynamically and synergistically.
Environmental Factors
Environmental factors – diet, climate, smoking,
alcohol, drugs, pollutants, and environmental
toxins – may cause wide variations in
pharmacological response within an individual
and even wider variations between groups of
individuals.43 Several of these factors can
operate simultaneously in the same individual,
thus affecting the processes of drug absorption,
distribution, metabolism, excretion, and
receptor interaction in different ways and to
different degrees.44
Differences in diet may significantly alter the
metabolism rate or the amount of a drug
present in the blood among different ethnic
populations. Studies comparing the metabolism
of a specific drug (antipyrine) between Asian
Indians in rural villages and Indian immigrants in
England demonstrated that, as immigrants
adopted the lifestyle and dietary habits of the
British, their drug metabolism accelerated.
12
AND
Similar findings have been observed among
Sudanese and Western Africans.45
Additionally, smoking can be an important factor
in determining response to pharmaceuticals.
This is of particular note since cigarette smoking
accelerates the metabolism of many
prescription drugs commonly used to treat
chronic diseases such as asthma and high blood
pressure, thereby making them less effective.
However, some drugs used to treat these
conditions are not affected by smoking;
prescribing can be individualized to use these
agents in smokers.46
Smoking-related disease and mortality is
disproportionately prevalent among African
Americans. Up to 45 percent of urban-dwelling
African Americans reported that they were
smokers, compared with 25 percent for the
general population.47,48 The smoking patterns of
African Americans are very different from those
of whites.49 African Americans smoke fewer
cigarettes per day (15 vs. 25 for whites), prefer
mentholated and higher tar or nicotine
cigarettes, and are more likely to smoke within
10 minutes of awakening.49,50 African Americans
also metabolize nicotine more slowly and have
higher serum nicotine metabolite levels per
cigarette smoked than whites.9,10 They may also
develop dependence at lower levels of smoking,
making it more difficult for them to quit.49,51,52 The
success rate for blacks who try to quit smoking
is 34 percent lower than for whites.49 Sustained
release bupropion has been found to be
particularly effective as an adjunct to help
African Americans quit smoking.53 The drug
seems to alter nicotine metabolism in blacks
more than whites, in addition to its known
effect as an antidepressant.
Genetic Factors*
Although age and gender affect drug response,
the primary biological factor impacting the
effectiveness of properly followed treatments is
genetics. Studies of twins and blood relatives
have shown that genetic differences are the
major biological factors determining the normal
variation in drug effects, and are responsible for
many differences in drug activity among healthy
subjects studied under carefully controlled
environmental conditions. More than 100
examples have been documented in which
inherited individual traits were implicated in
atypical, exaggerated responses to drugs, novel
drug effects, or lack of effectiveness of drugs.54
The genetic makeup of an individual may
change the action of a drug in a number of ways
as it moves through the body. Genetic factors
may influence a drug’s action by altering its
pharmacokinetic properties (absorption,
distribution, metabolism, excretion) or
pharmacodynamic properties (effect on the
body). Clinically, there may be an increase or
decrease in the intensity and duration of the
expected typical effect of the drug.
...genetic differences are the major biological factors
determining the normal variation in drug effects.

Human Migration: The Distribution of Genetic Polymorphisms

Anatomically modern humans evolved in Africa about 100,000 years ago.55 Some of these people
migrated from East Africa into Eurasia, and subpopulations spread east into southern Asia. Australia
was inhabited around 50,000 years ago (and subsequently remained completely isolated from the rest
of the world until the late 18th century). Modern humans first inhabited Western Europe about 40,000
years ago. The northern latitudes were penetrated quite late. Following the habitation of Siberia 15,000
to 35,000 years ago, humans spilled into Alaska and rapidly occupied the whole of the North and
South American continents. The Pacific islands were colonized by peoples originating in South China
beginning about 5500 years ago and continuing into the historic period.56 Human populations
continued to migrate throughout prehistoric and historic times, displacing, coexisting, or intermixing
with indigenous peoples. The result is that there are no distinct geographic boundaries between
genetic variations; rather, there are gradations in the prevalence of polymorphisms across
geographical distance.

Two factors led to genetic differences among peoples and hence potential
differences in drug response. First, genetic mutations continued to arise
spontaneously in populations that were geographically isolated from one
another. These mutations were subject to environmental selection. Second,
because these population movements were initiated by subgroups of
people, they tended to represent only a particular subset of the genetic
polymorphisms that were present in the entire human population. The
smaller the migrant subgroup, the more genetically distinct it would be from
other subgroups – a phenomenon called the “founder effect” – leading to
distinct patterns of polymorphisms in the descendent populations.

*Much of the material in this section is derived from: Burroughs VJ, Maxey RW, Levy RA.Racial and ethnic differences in
response to medicines: Towards individualizd pharmaceutical treatment. Journal of the National Medical Association.
2002;94(9)(suppl)1-26.

13
 The study of genetically determined variations in
drug response is called pharmacogenetics.
Variations in drug response are caused by gene
polymorphisms, which are naturally occurring
variations in the structures of genes, drug
metabolism enzymes, receptor proteins, and
other proteins involved in drug response or
disease progression. Pharmacogenetics
traditionally meant the study of polymorphisms
in individual genes. This field now has broadened
into pharmacogenomics, which examines the
effects of multiple genes on drug response. In
pharmacogenomics, large arrays of genes are
studied in parallel, so that the entire spectrum of
genes that determine the response to a
particular drug can be examined at one time.
Clinical relevance of genetic differences
(polymorphisms)
Common polymorphisms in drug metabolism
genes have received the most attention
because they affect the metabolism of many
clinically important and commonly used drugs.
Polymorphisms in these genes most often
affect drug metabolism by reducing it,
sometimes by disrupting it, and occasionally by
enhancing it. Individuals who do not metabolize
a certain drug efficiently are called “poor
metabolizers,” as opposed to normal or
“extensive metabolizers.”
Poor metabolizers process drugs over a longer
period of time, increasing not only the length of
time the body is exposed to a given drug, but
also the concentration of the drug in the
Factors Determining the Clinical Importance
of a Genetic Variation in Drug Metabolism54
1. There is a notable difference between extensive
metabolizers and poor metabolizers in how the drug
affects the body.
2. The drug has a narrow therapeutic index.
3. The dosage of the drug is not individually evaluated
on the basis of the therapeutic effect.
4. The drug is widely used by many physicians, not only
by clinical specialists.
14
bloodstream, creating the equivalent of an
overdose. Poor metabolizers generally do not
experience increased effectiveness because
dosages are normally targeted to have optimum
efficacy and higher dosages do not further
increase the effect. However, they often do
experience increased adverse events as if they
had been given a dose that is too strong. In
sum, poor metabolizers have a decreased
therapeutic ratio (efficacy:toxicity) for the
specific drug.57
It is important to note whether a given
polymorphism has clinical relevance in drug
therapy. Several factors determine the clinical
importance of a genetic polymorphism:54
• First, polymorphisms only have clinical
importance when they result in large
differences between poor metabolizers and
extensive metabolizers.
• Second, differences are relevant chiefly if
the drug has a small therapeutic index, i.e.,
the ratio of its therapeutic effect to its
adverse effects.
• Third, if physicians adjust drug dosage based
on the therapeutic effect (as is common
practice with drugs to treat high blood
pressure), then differences between poor
and extensive metabolizers are automatically
corrected.
• Fourth, the clinical implications are broader
for widely prescribed drugs such as beta-
blockers and tricyclic antidepressants because
more patients in more population subgroups
are affected.
Most pharmacogenetic studies have
concentrated on several groups of drugs and
their activity in certain populations. These drug
groups include cardiovascular agents and central
nervous system agents (Table 1). Cross-racial
variability in the action of drugs in these
categories is clinically significant and results
from differences in pharmacokinetic or
pharmacodynamic factors, or in the
pathophysiology of disease.
Table 1. Drug Showing Varying Effects Among Racial and Ethnic Groups58,59,60,61,78,62,43

Drug Comparison Groups Blood Concentration Clinical Response

of Drugs
CARDIOVASCULAR DRUGS
ACE INHIBITORS
High blood pressure and hospitalization for
Enalapril Blacks vs. Whites N/A heart failure is reduced in whites but not in
blacks with left ventricular dysfunction
Effect in lowering blood pressure is greater
Captopril Blacks vs. Whites N/A
in whites
BETA-BLOCKERS
Relaxing of the blood vessels is markedly
Isoproterenol Black vs. White men N/A lower in blacks
Chinese are twice as sensitive to effects
Propranolol Chinese vs. Caucasians Lower in Chinese on blood pressure and heart rate
Effect in lowering blood pressure is greater
Propranolol Blacks vs. Whites N/A in whites
CALCIUM CHANNEL BLOCKERS
South Asians vs. Threefold higher in
Nifedipine N/A
Caucasians South Asians
Nifedipine Koreans vs. Caucasians Greater in Koreans N/A

Nifedipine Nigerians vs. Caucasians Greater in Nigerians N/A

DIURETICS
71% of blacks achieved blood pressure
Hydrochlorothiazide Blacks vs. Whites N/A goal vs. 55% of whites in Veterans
Administration study

CENTRAL NERVOUS SYSTEM AGENTS

ANTIDEPRESSANTS
Asians, (Indian, Pakistani) Higher incidence and severity of side
Clomipramine Greater in Asians
vs. Whites (English) effects in Asians
Nortriptyline Japanese vs. American Greater in Japanese N/A
BENZODIAZEPINES
Alprazolam Asians vs. Caucasians Lower for Asians N/A
ANTIPSYCHOTICS
Clinically adjusted dose is lower in
Korean Americans vs.
Clozapine N/A Koreans, and Koreans have a higher rate of
Caucasians
central nervous system side effects
Asians (Chinese, Japanese,
Effective dose and optimal response
Haloperidol Filipino, Korean, No difference
threshold are lower for Asians
Vietnamese) vs. Caucasians
Chinese vs. non-Chinese Higher mean blood levels in
Clinically adjusted dose is lower for
Haloperidol (Caucasians, Hispanics, Chinese than in Americans
Chinese than for non-Chinese
Blacks) (when given same dose)
Caucasians vs. American- Higher for Asians than for
born Asians vs. foreign-born Caucasians. Similar for
Haloperidol Asians (Chinese, Filipino, American-born and foreign- No difference in side effects
Japanese, Korean) born Asians.

15
N/A, not available.
 Racial differences in response to medications
As shown in Table 1, drugs used to treat
conditions affecting the cardiovascular system
and the central nervous system are frequently
susceptible to the effects of genetic
polymorphisms. Within the black population, the
cardiovascular effects are especially notable.
High blood pressure is disproportionately
prevalent in the black population and is
associated with higher incidences of
cerebrovascular and kidney complications and
enlargement of the heart. However, the overall
risk of coronary artery disease in the black male
population is lower than that in white males,
particularly in Europe and the Caribbean, and to
a lesser extent in the U.S.
There are general differences in the underlying
causes of high blood pressure between the
black and white populations. For instance, black
patients retain more salt and therefore have a
higher incidence of salt-sensitive high blood
pressure. These factors may underlie some of
the observed differences in the effectiveness of
various high blood pressure drugs in black
populations. Ultimately, the choice of therapy
must be tailored to the individual patient.
Hispanic patients have been reported to require
lower doses of antidepressants and to
experience more side effects compared with
Caucasians.
Although there is a long-standing discussion
about the best type of drug to use for treating
high blood pressure in black patients,63 African
Americans respond to drugs from all classes.2,64
There is no specific class of high blood pressure
drugs that categorically should not be used
based on race. Diuretics are frequently used to
counteract increased salt retention among
blacks. Although some studies find that beta-
blockers, ACE inhibitors, and angiotensin
receptor blocking agents do not control blood
pressure in African Americans with the same
degree of effectiveness as in whites, targeted
blood pressure levels can usually be achieved by
adding a second agent such as a low-dose
diuretic.65,66,67,68,69
16
The Veterans Administration Cooperative
Studies showed that blacks may respond
differently to different beta-blockers. For
example, the beta-blockers propranolol, nadolol,
atenolol, and penbutolol were less effective
among blacks than whites, but this differential
effect can be eliminated by the addition of a
diuretic. ACE inhibitors can be as effective in
blacks as calcium channel blockers or diuretics,
and in some cases they may be more effective
as a first-line treatment. However, because
lower doses of ACE inhibitors can be less
effective in black patients, higher doses may be
required than are normally prescribed.70,71,72 In
patients with high blood pressure complicated
by the presence of other medical conditions
such as diabetes, ACE inhibitors are first-line
agents in black as well as white patients.73
However, ACE inhibitors appear to be less
effective in black populations for the prevention
and treatment of heart failure in some patients.
Within Asian groups, central nervous system
agents show similar susceptibility to genetic
polymorphisms. In one study, lower dosages of
antidepressants were found to be effective for
Asians compared with Caucasians.45 Asians
living in diverse areas of the world (Los Angeles,
St. Louis, Hong Kong, and Beijing) have also
shown consistently slower metabolism of
tranquilizers, suggesting that genetic factors are
more important than environmental factors in
controlling the metabolism of these agents.45
Tricyclic antidepressants have a narrow
therapeutic index and therefore are among the
most commonly affected central nervous
system agents. Poor metabolizers and ultra-
extensive metabolizers of these drugs may have
clinical problems when they are taken at usually
prescribed doses. Poor metabolizers often
develop elevated blood concentrations, which
may result in adverse effects. These side effects
are rarely life threatening, but they are
sufficiently unpleasant to cause problems with
patient compliance. Ultra-extensive
metabolizers, on the other hand, may not
respond to recommended doses because drug
concentrations are too low to be effective.
Hispanic patients have been reported to require
lower doses of antidepressants and to
experience more side effects compared with
white non-Hispanics. Likewise, for a given dose
of an antidepressant, African Americans
achieved higher blood levels and faster
therapeutic response, but also more side effects
compared with whites.74
Ethnic groups such as Ashkenazi Jews may also
respond differently to antipsychotic agents,
especially with regard to side effects. A drug
used to treat schizophrenia was associated with
the development of a potentially life-threatening
blood disorder in 20 percent of Jewish patients,
although this adverse reaction develops in only
about one percent of chronic schizophrenic
patients in the general population.75 Genetic
testing revealed that all of the affected
Ashkenazi Jewish patients possessed a specific
set of genes that is found in 83 percent of
patients who developed the disease, but that
these genes were found in only 8 percent of
schizophrenic patients who did not develop the
reaction. This set of genes occurs in 10 to 12
percent of the Jewish population in Israel and
the U.S., but is characteristically found in less
than one percent of the total Caucasian
population of the U.S. The increased
susceptibility of Ashkenazi Jews in this study to
the development of this blood disorder as a
result of drug therapy may be due to the more
common presence of these genes among this
ethnic group.76
Medicines used to treat pain, such as codeine,
can be influenced by genetic polymorphisms.
This may have important clinical implications
since codeine is often a drug of first choice for
the treatment of chronic severe pain. Ten
percent of codeine is metabolized in the body to
morphine, from which it derives its pain
relieving effect. Poor metabolizers of codeine
therefore receive no therapeutic effect from the
drug, even at higher doses.77 Five to 10 percent
of white patients, vs. 1 percent of Asians, lack
an enzyme that converts codeine to morphine.
But even the 99 percent of Asians who do
convert codeine to morphine experience a
Trust is a vital determinant of
treatment adherence and,
ultimately, may be more important
to therapeutic outcome than any
procedure or medication.
weaker effect than do whites, since they clear
morphine faster and metabolize more rapidly
that portion of codeine that is not converted to
morphine.78
Medicines used to treat pain, such as codeine,
can be influenced by genetic polymorphisms
affecting central nervous system agents.
Cultural Factors
Cultural or psychosocial factors, such as the
attitudes and health beliefs held by various
groups, may affect the effectiveness of, or
adherence to, a particular drug therapy. However,
all persons from different ethnic and cultural
groups share the universal need to be heard, to
be respected, and to be valued. There also are
some common cultural themes shared by all of
the major ethnic groups. These themes can be
organized into issues of trust and respect, health
beliefs and practices, and family values. Although
clearly not confined to a particular population,
some specific themes may be more characteristic
of some cultural groups than others.79
Trust and respect
Sensitivity, understanding, and respect are
essential to building trust. Trust is a vital
determinant of treatment adherence and,
ultimately, may be more important to
therapeutic outcome than any procedure or
medication. Trust is generated within the
context of doctor-patient interactions, as
illustrated below:
• Some cultural groups place great reliance on
eye contact, body posture, and other
non-verbal communications (facial
expressions, nods of the head, tone of voice).
When there is a language barrier, such body
language assumes even greater importance.
• Physical contact is important to some patients
who may feel slighted if the doctor does not
touch them. To others, some physical touching
may represent a cultural taboo particularly
when related to gender differences.
17
 • Folk religion and healing rituals can be an
important influence in the culture of working
class immigrants, and a negative response to
these rituals from the physician may be
construed as a direct assault on their beliefs or
religion. For example, newly arrived Hispanic
immigrants in East Harlem often favor folk
medicine and midwives, the type of health
care familiar to them in the rural areas of their
homeland, because they believe that medicine
prescribed by an American health care
provider is made of harmful chemicals and is
therefore toxic. An example of this is an eight-
year-old girl with AIDS who is prescribed
several medications. “Although the purpose
and side effects of each medication have been
explained to her grandmother, she continues
to use herbal remedies for her
granddaughter’s affliction instead.”80
• Another study of the use of folk healing and
healers by Latinos from Columbia, the
Dominican Republic and Guatemala living in
New England found that “a major reason for
not using mainstream health care providers
more frequently was the perceived lack of
holistic care and the use of medicines that are
not natural.”81 Family nurse practitioners
working with Mexican-Americans report that
some of their clients are skeptical of Western
medicine and only seek it when self-treatment
and folk-healing have been unsuccessful.82
• For patients accustomed to a more formal
relationship with their providers, a casual
appearance or attitude may be detrimental to
the development of respect and trust.
• Providers may exhibit discriminatory behaviors
toward minority patients by not involving
them in health education or preventative
medicine programs, believing they lack
the necessary skills or are otherwise unable
to benefit. As a result, referrals to specialists
such as nutritionists or diabetes educators
are sometimes delayed until the disease
is advanced.
18
• Some groups have an inherent distrust of the
American health care system. Newly arrived
Latinos in East Harlem viewed health care
workers as extensions of government
agencies and feared deportation or other
negative consequences.80 For people of African
heritage, there is a fear of being poisoned: the
Tuskegee Syphilis Study is often cited as
validating perceptions of racism and
mistreatment.
Health Beliefs and Practices
Although cultural beliefs should be accorded
respect, misinformation or lack of information
should also be addressed. Problems may occur
when patients do not tell their physician that
they are taking herbal remedies or are seeing an
alternative medicine practitioner. For example,
38 percent of Native American patients in an
urban health center consulted with a Native
American healer, and patients rated their
healer's advice higher than their physician's
advice 61 percent of the time.83 Only 15 percent
of those seeing healers disclosed this to their
physician. In another study, 83 percent of older
Latin patients who reported using an alternative
therapy in the previous month did not tell their
physicians.84
Patients’ beliefs regarding the properties and
effects of medications are of central importance
in determining compliance with treatment
regimens. The following are examples of the
complex influence of health beliefs and
practices:
• Traditional healing is important among a variety
of population groups, and a dual system of
health care services often exists. In a study of
diverse populations in a metropolitan area, folk
medicine remedies were used in addition to,
rather than in place of, formal biomedical
health care.85 Although individuals from
different populations often use traditional
practitioners and treatments, mixed use of
these health care alternatives appears to be
the most common pattern. Most
complementary and alternative medicine
therapies are used by U.S. adults in
conjunction with conventional medical
services. The overall use of these therapies
 was higher for white non-Hispanic persons
(31 percent) than for Hispanic (20 percent) and
black non-Hispanic persons (24 percent).86
• Attitudes toward diet, exercise, smoking,
drinking, and body image are imbedded in all
cultural beliefs and practices, and these
attitudes affect health and interactions with
providers in important ways.
• Among some culturally-based attitudes is the
belief that people should keep their illnesses
to themselves. Persons holding such beliefs
may be likely to seek treatment at later stages
of the disease.
• The belief in fatalism exists among some
populations, which can influence attitudes
toward chronic disease. Even among young
children, an attitude of passive acceptance is
common. A fatalistic attitude impedes a direct
confrontation with the consequences of
unhealthy behaviors such as smoking.
• Among a group of older individuals in
California, it was found that in contrast to
African Americans, Latinos did not hold
mainstream Western views about health and
the management of illness.87 In fact, many
Latinos appeared not to understand the
meaning of “chronic” relating to illness, or
their role in managing their illness beyond
taking medication. They knew they must take
their medication, but usually the
disappearance of symptoms as a result of the
medication was taken to be a cure. Each new
episode was seen as a separate illness
unrelated to previous episodes, particularly in
illnesses with multiple symptoms. In addition,
Mexican and Puerto Rican patients were
found to be concerned about the addictive and
toxic effects of medication, and thus reluctant
to take medications indefinitely.88,89
Folk religion and healing rituals can be an
important influence in the culture of
working class immigrants, and a negative
response to these rituals from the
physician may be construed as a direct
assault on their beliefs or religion.
• Immigrant minority groups may have access
to controlled substances and other
medications not generally available in the U.S.
For example, antibiotic, neuroleptic, anti-
emetic, and most other prescription drugs are
easily obtained over the counter in Brazilian
pharmacies, and many pain-relieving
medicines are available without a prescription.
Once in the U.S., it becomes difficult to obtain
these drugs and persons requiring them on a
regular basis often request friends to bring a
supply from Brazil.90 In Haiti, many
medications can be purchased without a
prescription, so Haitians are often accustomed
to keeping numerous topical and oral
medicines on hand to treat various symptoms.
For example, an individual who suspects a
venereal disease may buy penicillin injections
and have someone administer them without
consulting a physician.90
19
 Problems with Alternative Remedies
The use of alternative remedies and supplements is common. Among a multi-ethnic population,
10.4 percent were regular users of alternative medicines; 7.4 percent regularly used non-
prescribed vitamin supplements; and 5.3 percent used cod liver oil, primrose oil, or garlic
preparations. People of African origin were more likely to use alternative medicines
than either whites or South Asians, who were the least common users.91

However the use of complementary and alternative medications can result in drug
interactions, disease interactions, adverse reactions, or toxic effects:

• An evaluation of the use of alternative preparations in the El Paso, Texas region

identified 599 instances of use of such remedies that could result in these effects,
based on interviews with 547 survey participants.92

• A survey of Spanish-speaking Latino families visiting a pediatric clinic in Salt Lake

City found that 39 percent of parents from Mexico and 21 percent from other
countries reported using a nonsteroidal anti-inflammatory drug (metamizole)
associated with a blood disorder side effect.93 The drug is available over-the-counter
in Latin American countries and in markets serving immigrant communities in the
U.S.

• Dozens of Chinese herbal remedies available in the U.S. contain the toxin aristolochic
acid. The toxin was implicated in an outbreak of kidney trauma in Belgium, possibly
causing cancers in more than 30 people, and is suspected of the same in several
other countries.94 Another study found clinically relevant liver enzyme elevations in
about 1 of 100 patients treated with traditional Chinese drugs.95

Family Values support and better clinical outcomes than their

The strengths of the African American, Asian,
Hispanic, and Native American family values,
along with extended family, church and
community organizations, can be important
resources in supporting the patient and in
facilitating adherence to medication and other
treatment regimens. Such networks can provide
substantial support in times of illness.
• Opinions of Asian family members and other
elders are accorded great respect in times of
illness. In Hispanic families, the mother or
grandmother (of the husband especially)
usually makes the health care decisions. In
addition, the needs of the children are always
paramount. Health care providers need to be
aware of these relationships to optimize
adherence to treatment regimens.
Western counterparts. Patients whose family
members expressed frequent criticism,
hostility, and emotional over-involvement
relapsed more frequently and required higher
doses of medication.96,97
• Despite the wide use of a variety of non-
Western treatments, the actual remedies may
not be perceived to be as critical to care as
the meaning of the cultural memories inherent
in acts of caring. For example, within Puerto
Rican and African American groups, comfort,
nurturance, and familiarity were found to be
“intrinsic to the holistic nature of the
remedies used and to be salient features of
the memories of healing and curing.”98

• Family atmosphere may influence response to

medications. Non-Western patients with
schizophrenia were found to have more social
20
Effect of cultural factors on medication
compliance
Patients’ beliefs regarding the properties and
effects of medications are of central importance
in determining compliance. For instance, some
patients from non-Western backgrounds are
unfamiliar with the practice of taking long-term
medication for chronic illness and with the
notion of accepting unpleasant side effects as
the price for effective treatment. These reasons
may account for why some patients stop taking
their medication.99 Variations in attitudes toward
medicines tend to be driven by national
characteristics, culture, and philosophy.100
Immigrants from countries with different non-
Western medical cultures may therefore have
different expectations regarding the type of drug
prescribed, tolerance of side effects, dosage
form preference, or other aspects of drug
therapy. This clash between patient and provider
expectations may result in noncompliance with
medications.
In comparison to other societies, American
medicine tends to be very aggressive, leading
to a greater focus on the effectiveness of
treatment and a greater tolerance of side
effects.100 Downward dosage adjustment by
Asian patients is common and results from the
perception that Western medicines are too
strong and that even relatively benign side
effects are intolerable.
In Japan, in general, a medicine’s safety profile is
stressed more than its effectiveness.101 This
“pharmaceutical conservatism” mirrors the
Japanese focus on slow and careful building of
personal relationships and consensus-based
business decisions.102 This emphasis on safety
and a systematic approach may explain, in part,
the general use of lower dosages compared with
dosages used in the West, and the lower
incidence of side effects reported by Japanese
compared with American and European
patients.102,103 In addition, patients in Japan
frequently are treated with multiple medications
because Asian patients often believe that multiple
drugs are more effective than monotherapy since
multiple herbal ingredients are usually prescribed
by traditional Asian doctors.104
European medicine reflects a middle-position
between the poles of American and Japanese
medical cultures. European practices differ in
terms of the patterns and types of drugs
prescribed, the preference for different dosage
forms (the French favor suppositories, Latin
Americans expect injections), and diagnoses in
some countries that are not used in others
(see100 for a detailed discussion).
Downward dosage adjustment by Asian
patients is common and results from the
perception that Western medicines are too
strong and that even relatively benign side
effects are intolerable.
There is also a general expectation among many
cultures that medicines will provide quick relief
from symptoms, and thus do not need to be
taken long-term. In some developing countries,
medications are customarily prescribed for only
a day or two.105 These beliefs may reflect their
experiences with indigenous herbal
preparations, which generally cause fewer side
effects, and with analgesics and antibiotics,
which work rapidly.28 Hispanics and Asians often
expect rapid results and are cautious about the
side effects of Western medicines.106,107 These
beliefs may interfere with the acceptance of
drugs with a delayed onset of action (e.g.,
antidepressants).
Lastly, poor health literacy may negatively
impact patients’ ability to take medications
properly. Members of groups for whom English
is a second language are more likely than
socioeconomically advantaged white adults to
have limited literacy skills, and there is a
relationship between low literacy and self-
management skills, including taking medications
properly.32,108
Some patients are unfamiliar with the
Western practice of taking long-term
medication for chronic illness and with the
notion of accepting unpleasant side effects
as the price for effective treatment.
21
 THE FUTURE OF INDIVIDUALIZED THERAPY
Technological advances in the 1990s have
changed the nature of pharmacogenetic
research and its future impact on medicine. In
the early decades of its existence,
pharmacogenetics focused on the enzymes
responsible for drug metabolism. Differences in
the genes encoding these enzymes were
inferred from differences in the structure and
activity of the enzymes themselves. The
frequencies of polymorphisms in drug
metabolism enzymes were observed to vary
among different populations defined on the
basis of race. Thus, race is one factor (among
many) that changes the probability that an
individual person will respond to a given drug.
Two features of the genomics revolution, with
the Human Genome Project as its centerpiece,
have important consequences for the
relationship between drug therapy and race.
First, genetic variations are now determined by
direct analysis of genes themselves. Gene
sequencing (i.e., determination of a gene’s
nucleotide sequences) has become a rapid and
automated process. Second, the entire
spectrum of genes that determine drug behavior
and sensitivity now can be studied genetically.
That is, the effect of the entire genome on drug
behavior can be determined rather than the
effect of the individual gene – hence the change
from pharmacogenetics to pharmacogenomics.
In a sense, it is now possible to take a genetic
“fingerprint” of an individual and precisely
determine the presence of polymorphisms in
the genes known to be involved in drug
interaction. Thus, instead of a person’s race
being a marker for the possession of
polymorphisms involved in drug response, a
genotypic profile can determine with certainty
whether or not the individual possesses these
polymorphisms.
It is now possible to take a genetic
“fingerprint” of an individual and
determine precisely the presence of
polymorphisms in the genes known to be
involved in drug interaction.
22
In the future, drug treatment will be individually
tailored rather than based on race or other
categories such as sex or age. However, the full
impact of these changes will take many years to
unfold. Genetic fingerprinting using DNA arrays
is already practical, but the knowledge base
relating genomic variations to drug response
and disease progression has not been
developed. Observational studies are under way
in which DNA fingerprints are being correlated
with data present in medical records about
medical history and drug response, and it is
expected that the medical records of an entire
country (Iceland) will be correlated with
genomic data. These developments will surely
have a profound impact on the ways in which
new drugs are developed and used.
Continuing research in
pharmacogenomics is likely to
reveal significant and far-ranging
information regarding inter-
individual and cross-racial
differences in the actions of new
and existing drugs.
Continuing research in pharmacogenomics is
likely to reveal significant and far-ranging
information regarding inter-individual and cross-
racial differences in the actions of new and
existing drugs. These developments, along with
the increasing prevalence and influence of
patients from a variety of races and ethnicities
and the continued pressure to manage health
care costs, will require programs having the dual
objectives of cost control and individualized
therapy for a racially and ethnically diverse
population of Americans. Balancing these
objectives will challenge health policy makers in
the coming decades.
CONCLUSIONS AND RECOMMENDATIONS
As a result of advances in pharmacogenetics
research, as well as political and social changes
affecting racial and ethnic groups, more
consideration is being given to the need for
individualized drug therapy. The availability of a
broad range of medicines enables physicians to
treat patients with precision and provides
options when the first agent used is ineffective,
not tolerated, or proper compliance is not
achievable. Often, one drug cannot simply be
substituted for another of the same class
because its clinical effects may vary among
racial and ethnic groups due to differences in
drug metabolism. In order for health care
practitioners to engage in racially and ethnically
appropriate prescribing, a wide range of options
must therefore remain available.
Policies that arbitrarily limit drug choices
stand in opposition to an increasing body of
evidence indicating that drug therapy does the
most good (and the least harm) when it is
tailored to the individual. Individualized
prescribing takes into account a number of
factors, among them environmental, genetic,
and cultural factors that may affect a drug’s
effectiveness and compliance with prescribed
treatment regimens.
These factors are relevant to the
implementation of pharmaceutical cost
management policies. Such policies must
consider any possible discriminatory effects on
racial and ethnic groups. Limiting access to
optimal medications may produce reduced or
unexpected responses in subpopulations.
Access to a variety of medications and dosing
formulations, especially those enabling
simplified administration (e.g., once-daily or
without regard to food) can facilitate compliance
and may be particularly beneficial for patients
with low health literacy who may have trouble
following complex instructions. Additionally,
patients with low health literacy or language
barriers may be ill-equipped to understand the
limitations of restrictive policies and the appeals
processes necessary to obtain a more
appropriate drug. Restricting access to
medications that will provide optimal care can
contribute to existing disparities in health care.
The following recommendations offer practical
suggestions that could not only benefit the
quality of care provided by health care
institutions and physicians, but could also be
useful in controlling health care costs.
1. Health care institutions should implement
pharmaceutical cost containment practices
that are broad and flexible enough to enable
rational choices of drugs and formulations for
all patients, regardless of race or ethnic origin.
2. Pharmaceutical companies should continue to
include significant numbers of patients from
varied racial and ethnic backgrounds in drug
metabolism and clinical trials in cases where
genetic polymorphism for that drug class is
relevant. The vast majority of drug
manufacturers test and evaluate new
pharmacological compounds on population
subgroups, including racial and ethnic
subgroups. This is likely to reveal drug actions
and side effects specific to these groups, and
may lead to the discovery of therapies of
specific advantage to these populations. It
may also reveal cultural barriers to use of the
drug among particular groups.
3. Hospitals, managed care groups, and other
providers of health care services should
endeavor to employ practitioners who are
racially and ethnically representative of the
patient population being served. There is,
however, a short supply of physicians from
backgrounds representing our most important
minority groups. Given this dearth of
providers, we must seek to train the existing
health care professionals to provide
appropriate care to culturally diverse clients.
Provider organizations should develop and
institute specific training for all practitioners
who have direct patient contact – especially
physicians, pharmacists, nurses, and
physician assistants.
4. Health care providers should give
individualized treatment to each patient. For
the practicing physician, each patient
represents a unique and dynamic interaction
among several determinants including
environmental, genetic, and cultural. Although
it may be impossible for a physician to
anticipate how a particular patient will
respond in every instance, it is imperative to
individualize therapy with respect to the
appropriate choice of both drug and dose, and
to make sure that the patient both
23
 understands and is able and willing to comply
with the prescribed treatment.
5. Physicians should be alert to atypical drug
responses or unexpected side effects when
they treat patients from varied racial and
ethnic backgrounds. Patients may not be
taking the medication properly due to
misunderstood instructions, or
misperceptions of Western medicine or
the severity of disease. Dosage adjustments
may need to be made for patients from
different groups as supported by
pharmacological evidence.
6. Providers should take special care to
communicate clearly and concisely with
patients for whom there may be a linguistic
communications barrier or a concern about
the patient’s level of health literacy. This also
24
involves perceiving and surmounting less
visible barriers such as patient confidence,
shame, or fear. Practitioners must be able to
communicate effectively across cultural,
socioeconomic, educational, and geographical
differences. Any written materials distributed
should be appropriate to the patient’s level of
health literacy and should reinforce spoken
dialogue.
7. Because advances in pharmacogenomics
will improve the ability to individualize
treatment, all who are involved in patient
care should actively monitor developments
in this area to take advantage of new
diagnostic and therapeutic technologies
as they become available.
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