CONTEMPORAR

Y ISSUES IN
PHARMACOLO
GY
The Drug Approval
Process
 The Drug Approval Process

Once a promising new candidate is identified, it is tested in preclinical studies (in vitro
systems and experimental animals).

Drugs that still look promising after these preclinical studies’ application of
investigational new drugs (IND) are filed with the DRA for testing in clinical trials first
in healthy people (Phase 0 and I) and then in people with the target disease (Phases II
and III). In phase 0, a very low dose of the drug is tested for the first time on human
subjects (10 to 15 subjects).

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The Drug Approval Process
Continuation…
Based on the pharmacogenetic or pharmacodynamic properties, a decision on
whether to start phase 1 or not is taken. These clinical trials assess safety and
effectiveness in human beings.

If the drug appears promising through three phases of clinical trials, the
manufacturer files application for approval of NDA from DRA to market the
drug.
It is important that the manufacturer and the DRA continue post-marketing
surveillance of new drugs (Phase IV) in real-life patients under diverse
conditions for early detection of risk of toxicity that occur rarely enough which
escapes detection in the clinical trials setting.

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The Drug Approval Process
⬢ Preclinical and clinical phases of drug evaluation: The drug
development path and objectives of various phases of the
clinical trials, the number of patients enrolled at each stage.

⬢ Patent protection and generic drugs: A company usually

patents novel/new chemical entities early in the drug
discovery process.

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Transcultural and
Genetic
Consideration
CULTURAL CONSIDERATION
⬢ Ethnomedicine, sometimes referred to as folk medicine or traditional
medicine, is a focus within medical anthropology that examines the ways in
which people in different cultures conceptualize health and illness.

⬢ These cultural constructs dictate healing practices. In many non-Western

cultures, there is the belief that illness is spiritually based rather than
biologically based. In some cultures, illness is thought to be caused by spirit
possession or by a loss of balance within the body. Healing techniques may
be based on astrology, magic, rituals, and indigenous medicinal compounds.

⬢ Traditional Healers play a role in health practices worldwide and can include
priests, shamans, bone setters, herbalists, curanderos, and midwives.

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CULTURAL CONSIDERATION
⬢ Ethnopharmacology is a subdivision of ethnomedicine and focuses on the
use of herbs, powders, teas, and animal products as healing remedies.

⬢ These traditional health practices can have neutral, beneficial, or deleterious

effects on a patient’s health.

⬢ The emergence of ethnopharmacology highlights the need for nurses to use

research from the social sciences, as well as the biological and physical
sciences, to provide holistic nursing care within a culturally competent
context.

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CULTURAL CONSIDERATION
⬢ Culture is based on learned beliefs and behaviors that are shared by
a group of people. Symbols, artifacts, institutions, values, mores,
and rules are the products of culture. Culture is not biologically
inherited. There are certain universals that are biologically driven,
such as the need to eat, but what is eaten and how it is eaten is
culturally driven.

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Transcultural Nursing
⬢ The concept of transcultural nursing was formalized by Madeleine
Leininger, a nurse anthropologist who founded the Transcultural Nursing
Society in 1974.
⬢ To provide culturally competent care, it is imperative that nurses be sensitive
to the beliefs and practices of immigrant and indigenous groups concerning
health and illness.
⬢ As part of the health history, it is important to determine all the
pharmacotherapeutic agents the patient is using.

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The Giger and Davidhizar
Transcultural Assessment
Model
⬢ The Transcultural Assessment model, developed by Giger and Davidhizar in
1998, depicts the six cultural phenomena of (1) communication, (2) space,
(3) social organization, (4) time, (5) environmental control, and (6)
biologic variation.

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Communication

⬢ Communication occurs verbally and nonverbally. Nurses must be

alert to different types of communication styles among patients to
provide culturally competent care.

⬢ When the patient and the health care provider speak different
languages, professional translators should be used whenever
possible to safeguard a patient’s confidentiality.

⬢ If a professional translator is not available, it is important that the

nurse select an alternative person carefully.

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Communication
⬢ Vernacular English and Standard English
⬢ Greetings and Communication Styles

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Space
⬢ The amount of space around a person’s body is an important
psychological consideration.

⬢ Americans often desire a great deal of personal space and value

privacy. In other cultures, population density dictates limited
personal space. Patients who are used to dense living quarters may
feel insecure in a hospital room. It is important that the nurse have
frequent contact with these patients and allow significant members
of the social group to remain with the patient as much as possible.

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Social Organization
⬢ Families are basic social units. The definition of family and the
criteria for inclusion vary among individuals and among cultures.

⬢ Nurses are in a position to advocate for inclusion of the family in

health care settings. Limiting the amount of time a patient can visit
with members of the social group is a long-standing practice in
American health care settings, but in some other countries, such as
the Philippines, it is expected that family members will stay by the
patient’s bedside and participate in his or her care.

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Time
⬢ Nurses and patients are likely to have different perceptions of time.
Time moves slowly for a patient who is anxious or in pain but
moves quickly for a nurse who has a demanding workload.

⬢ The use of vague terms to denote time may also cause a disparity
between nurses’ and patients’ perceptions of time. Words like soon,
about, or later may have vastly different nuances among individuals
and groups.

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Environmental Control
⬢ A major aspect of some cultures is the desire to enlist the assistance
of nature to facilitate the needs of human beings. The concept of
“nature” may include otherworldly forces or beings, such as deities
and spirits.

⬢ Healers and spiritual advisors can be beneficial in health care

settings; examples include the practice of clergy (e.g., ministers,
priests, rabbis) visiting ill members of a congregation or the
inclusion of a traditional healer in the plan of care.

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Biologic Variations
⬢ The Genographic Project was conducted by National Geographic
scientists and performed DNA testing on populations all over the
world. Findings reveal that human beings are 99.9% genetically
identical.
⬢ To illustrate the significance of these findings in patient care
settings, it is necessary to review additional terms used in the field
of pharmacogenetics.
⬢ Genomes are a complete set of chromosomes and make up a cell’s
DNA.
⬢ Polymorphisms are DNA variants that occur within a specific
population at a frequency greater than 1%. A substrate is a
substance that binds to and is metabolized by one or more enzymes.
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Pharmacogenetics
⬢ Refers to the study of all the different genes
that determine drug behavior within the
human body. Culturally competent care
integrates pharmacogenetics with the social
and cultural attributes of the patient, which
helps to predict variations in drug responses.

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Pharmacogenetics
⬢ Mapping of the human genome has instilled hope for
improving diagnosis and treatment of disease,
predicting disease potential based on genetic
predisposition, and personalizing medicine based on
genetic profiles. However, as with drugs not being
“one size fits all,” use of pharmacogenetics is not
appropriate for all patients.

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Individual Variation In
Metabolism of Select Drugs
Mercaptopurine.

The FDA recommends genetic testing before the administration of

mercaptopurine to patients with acute lymphoblastic leukemia. Genetic
variation in thiopurine S-methyltransferase (TPMT) can interfere with
the metabolism of the drug, leading to an increased severity in side
effects and increased risk of infection.

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Individual Variation In
Metabolism of Select Drugs
Warfarin.

This drug is a vitamin K antagonist used for prophylaxis and treatment

of venous thromboembolism and for persons with atrial fibrillation or
heart valve replacement, among other uses. It has a narrow therapeutic
range.

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Individual Variation In
Metabolism of Select Drugs
Clopidogrel.

Persons with genetic variation in the CYP2C19 enzyme, which is

necessary to convert the prodrug clopidogrel, an inhibitor of platelet
aggregation, to the active metabolite, may be at risk for clot formation
due to failure to convert the prodrug to active drug.

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Individual Variation In
Metabolism of Select Drugs
Opioids.
Codeine and tramadol are prodrugs that do not exhibit analgesic
properties until converted to active drug by the CYP2D6 138 enzyme in
the liver.

Mental Health Drugs.

Many drugs used to treat depression (e.g., tricyclic antidepressants and
selective serotonin reuptake inhibitors)
and other psychiatric disorders (i.e., aripiprazole for use in bipolar
disorder and schizophrenia, and atomoxetine for use in ADHD) are
metabolized by the CYP 2D6 enzyme.
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Individual Variation In
Metabolism of Select Drugs
⬢ Carbamazepine.

Persons with the human leukocyte antigen (HLA) B ∗1502 variant

should avoid using carbamazepine due to increased risk of developing
Stevens-Johnson syndrome or toxic epidermal necrolysis. Persons of
Asian descent are most likely to carry this genetic variant

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Drug
Interactions
What are Drug Interactions?

⬢ Anytime you take more than one medication, or even

mix it with certain foods, beverages, or over-the-
counter medicines, you are at risk of a drug
interaction. Most drug interactions are not serious, but
because a few are, it is important to understand the
possible outcome before you take your medications.

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Drug Interactions
⬢ is defined as an altered or modified action or effect of a
drug as a result of interaction with one or multiple drugs.

⬢ It should not be confused with drug incompatibility or an

adverse drug reaction, an undesirable drug effect that
ranges from mild untoward effects to severe toxic effects
that include hypersensitivity reaction and anaphylaxis.

⬢ Drug incompatibility is a chemical or physical reaction that

occurs among two or more drugs in vitro. In other words,
the reaction occurs between two or more drugs within a
syringe, IV bag, or other artificial environment outside of
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⬢ Drug interactions can be divided into two
categories,

a) Pharmacokinetic Interactions
b) Pharmacodynamic interactions

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Pharmacokinetic Interactions
⬢ are changes that occur in the absorption,
distribution, metabolism, and excretion of
one or more drugs.

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Absorption:
⬢ Some drugs can alter the absorption of another drug into your
bloodstream.
⬢ For example, calcium can bind with some medications and block
absorption. The HIV treatment dolutegravir (Tivicay) should not be
taken at the same time as calcium carbonate (Tums, Maalox,
others), because it can lower the amount of dolutegravir absorbed
into the bloodstream and reduce its effectiveness in treating HIV
infection. Dolutegravir should be taken 2 hours before or 6 hours
after medications that contain calcium or other minerals to help
prevent this interaction.
⬢ In the same manner, many drugs cannot be taken with milk or dairy
products because they will bind with the calcium. Drugs that affect
stomach or intestine motility, pH, or natural flora can also lead to
drug interactions.
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Distribution:
⬢ Protein-binding interactions can occur when two or more highly
protein-bound drugs compete for a limited number of binding sites
on plasma proteins. One example of an interaction is between
fenofibric acid (Trilipix), used to lower cholesterol and
triglycerides in the blood, and warfarin, a common blood thinner
to help prevent clots.
Fenofibric acid can increase the effects of warfarin and
cause you to bleed more easily.

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Metabolism:
⬢ Drugs are usually eliminated from the body as either the unchanged
(parent) drug or as a metabolite that has been changed in some way.
Enzymes in the liver, usually the CYP450 enzymes, are often
responsible for breaking down drugs for elimination from the body.
However, enzyme levels may go up or down and affect how drugs
are broken down.
⬢ For example, using diltiazem (a blood pressure medication) with
simvastatin (a medicine to lower cholesterol) may elevate the
blood levels and side effects of simvastatin. Diltiazem can inhibit
(block) the CYP450 3A4 enzymes needed for the breakdown
(metabolism) of simvastatin. High blood levels of simvastatin can
lead to serious liver and muscle side effects.
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Excretion:
⬢ Some nonsteroidal anti-inflammatory drugs
(NSAIDs), like indomethacin, may lower
kidney function and affect the excretion of
lithium, a drug used for bipolar disorder.
You may need a dose adjustment or more
frequent monitoring by your doctor to safely
use both medications together.

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Pharmacodynamic Interactions
⬢ occurs when two drugs given together act at the same
or similar receptor site and lead to a greater (additive
or synergistic) effect or a decreased (antagonist)
effect.
⬢ For example, when chlorpromazine, sometimes used
to help prevent nausea and vomiting, and
haloperidol, an antipsychotic medication for
schizophrenia, are given together there may be a
greater risk for causing a serious, possibly fatal
irregular heart rhythm. 41
Pharmacodynamic Interactions
⬢ Additive Drug Effects, When two drugs are
administered in combination, and the response is increased
beyond what either could produce alone, the drug
interaction is called an additive effect; it is the sum of the
effects of the two drugs. Additive effects can be desirable or
undesirable.

⬢ For example, a desirable additive drug effect occurs when a diuretic and a
beta blocker are administered for the treatment of hypertension. In
combination, these two drugs use different mechanisms to have a more
pronounced blood pressure–lowering effect. As another example, aspirin
and codeine are two analgesics that work by different mechanisms but can 42
Pharmacodynamic Interactions
⬢ Synergistic Drug Effects and Potentiation When two or
more drugs are given together, one drug can have a
synergistic effect on another. In other words, the clinical
effect of the two drugs given together is substantially
greater than that of either drug alone.

⬢ An example of this is the use of two cytotoxic drugs to reduce individual

drug dosing, thereby decreasing side effects. An example of an undesirable
effect occurs when alcohol and a sedative-hypnotic drug such as diazepam
are combined. The resultant effect of this example is increased CNS

depression .
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Pharmacodynamic Interactions
⬢ Antagonistic Drug Effects, When drugs with antagonistic
effects are administered together, one drug reduces or blocks the
effect of the other. In some situations, antagonistic effects are
desirable. In morphine sulfate overdose, naloxone is given as an
antagonist to block the narcotic effects of morphine sulfate.
⬢ This is a beneficial drug interaction of an antagonist. Likewise, in
the case of heparin overdose, protamine sulfate is administered to
block the effects of heparin.
⬢ The most common symptoms of drug-drug interactions include
nausea, heartburn, headache, and lightheadedness.

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Drug-drug Interaction
⬢ These are the most common type of drug interaction. The more
medications you take, the greater the chance for your drug
interacting with another medicine.
⬢ Drug-drug interactions can decrease how well your medications
work, may increase minor or serious unexpected side effects, or
even increase the blood level and possible toxicity of a certain drug.
⬢ For example, if you take a pain medication, like Vicodin, and a
sedating antihistamine, such as Benadryl, at the same time you will
have an additive amount of drowsiness as both medications cause
this side effect.

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Drug-food/beverage Interactions
⬢ You have probably seen the stickers on your prescription bottle to
“avoid grapefruit juice” at one time or another. This may seem
odd, but certain medications can interact with foods or beverages.
For example, grapefruit juice can lower the levels of enzymes in
your liver responsible for breaking down medications. Blood levels
of an interacting drug may rise, leading to toxicity.

⬢ This interaction can occur with the commonly used statins to lower
cholesterol, like atorvastatin, lovastatin, or simvastatin. The result
can be muscle pain, or even severe muscle injury known as
rhabdomyolysis.

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Drug-disease interactions
⬢ Drug interactions don't always occur with just other drugs or foods.
Your existing medical condition can affect the way a drug works,
too.

⬢ For example, over-the-counter oral decongestants like

pseudoephedrine (Sudafed) or phenylephrine (Sudafed PE) may
increase blood pressure and can be dangerous if you have high
blood pressure.

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Over-the-Counter
Drugs
Over-the-Counter Drugs
⬢ OTC - are products that are available without
prescription for self treatment of a variety of
complaints.
⬢ OTC drugs are medications that are safe and
effective for use by the general public
without seeking treatment by a health
professional.

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Over-the-Counter Drugs
⬢ In 2002, the FDA standardized OTC labeling to
provide consumers with better information and to
describe the benefits and risks associated with taking
OTC drugs.

⬢ It is an important nursing responsibility to ensure that

patients are able to read and understand OTC labels.

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Over-the-Counter Drugs
⬢ All OTC drugs must have labels that provide the following
information in this specific order.

• The product’s active ingredients, including the amount in each dosage unit
• The purpose of the product
• The uses (indications) for the product
• Specific warnings, including when the product should not be used under
any circumstances, substances or activities to avoid, side effects that could
occur, and when it is appropriate to consult with a doctor or pharmacist
• Dosage instructions that include when, how, and how often to take the
product
• The product’s inactive ingredients and important information to help
consumers avoid ingredients that may cause an allergic reaction.

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 Nursing Considerations Related
to Over-the-Counter Drugs
Nurses should advise patients of the following when over-the-counter (OTC)
drugs are considered:
⬢ • Always read the instructions on the label.

⬢ • Do not take OTC medicines in higher dosages or for a longer time

than the label states.

⬢ • If you do not get well, stop treating yourself and talk with a health
care professional.

⬢ • Side effects from OTCs are relatively uncommon, but it is your

job to know what side effects might result from the medicines you
are taking. 53
 Nursing Considerations Related
to Over-the-Counter Drugs
⬢ • Because every person is different, your response to the medicine
may be different than another person's response.

⬢ • OTC medicines often interact with other medicines, and with food
or alcohol, or they might have an effect on other health problems
you may have.

⬢ • If you do not understand the label, check with the pharmacist.

⬢ • Do not take medicine if the package does not have a label on it.

⬢ • Throw away medicines that have expired (are older than the date
on the package).
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Nursing Considerations Related to
Over-the-Counter Drugs
⬢ • Do not use medicine that belongs to a friend.

⬢ • Buy products that treat only the symptoms you have.

⬢ • If cost is an issue, generic OTC products may be cheaper

than brand name items.

⬢ • Avoid buying these products online, outside of well-

known Internet insurance company sites, because many
OTC preparations sold through the Internet are counterfeit
products. These may not be what you ordered and may be
dangerous.
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 Nursing Considerations Related to
Over-the-Counter Drugs
Parents should know the following special information
about using OTCs for children:

⬢ • Parents should never guess about the amount of

medicine to give a child. Half an adult dose may be too
much or not enough to be effective. This is very true of
medicines such as acetaminophen (Tylenol) or ibuprofen
(Advil), in which repeated overdoses may lead to
poisoning of the child, liver destruction, or coma.
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Nursing Considerations Related to
Over-the-Counter Drugs
⬢ • If the label says to take 2 teaspoons and the dosing cup is marked
with ounces only, get another measuring device. Don't try to guess
about how much should be given.

⬢ • Always follow the age limits listed. If the label says the product
should not be given to a child younger than 2 years, do not give it.

⬢ • Always use the child-resistant cap, and relock the cap after use.

⬢ • Throw away old, discolored, or expired medicine or medicine that

has lost its label instructions.

⬢ • Do not give medicine containing alcohol to children 57

DRUG OF ABUSE
Substance Use Disorder

⬢ occurs “when the recurrent use of alcohol and/or

drugs causes clinically and functionally significant
impairment, such as health problems, disability, and
failure to meet major responsibilities at work, school,
or home.”

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Substance Use Disorder
⬢ street drugs—nonprescription drugs with no
known therapeutic use—to enhance their
moods and increase pleasure.

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Social risk factors:
⬢ Deviant peer relationships (i.e., the adolescent associates
with abusers and uses drugs to feel accepted)
⬢ Peer pressure
⬢ Popularity
⬢ Bullying
⬢ Gang affiliation is associated with higher drug use and
delinquent behavior.

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Individual risk factors:
⬢ Individuals with attention-deficit/hyperactivity
disorder (ADHD) are three times as likely as the
general population to use drugs such as nicotine,
alcohol, and drugs other than Cannabis
⬢ depression is associated with alcohol use, particularly
among young men.
⬢ It should be noted that positive family relationships
are a protective factor that has been related to a
decrease in drug use among adolescents.
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Types of Substance Use Disorders
⬢ Alcohol Use Disorder (AUD)
⬢ Cannabis Use Disorder
⬢ Opioid Use Disorder
⬢ Tobacco Use Disorder
⬢ Cough and Cold Products
⬢ Anabolic-Androgenic Steroids

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Frequently Abused Street Drugs and

“
Their Potential Health Consequences

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 “
“Every Nurse was drawn to
Nursing because of a desire
to care, to serve, or to
help.”
-Christina Feist-Heilmeier

THANK YOU!!!
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