Transcript GENA® Objective 16 excerpt - Native American Cancer Research

GENA® Objective 16
excerpt:
Pharmacogenetics
(an excerpt from NACI’s GENA® obj 16; used with
permission from Linda B)
QUESTION: What factors can influence how a
person responds to medication?
Weight
Diet
Obviously, many factors
Food in stomach affect people’s
Fatigue
responses drugs other
Age
than genes.
Sun exposure
Physical condition / lack of exercise
Drug interactions (i.e., Cross reactivity,
synergism)
Genetic make-up
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Definition of “Pharmacogenetics”
The study of how an
individual’s genetic
inheritance affects the
body’s response to drugs.
Pharmacology + genomics =
the interaction of
medications and genetics...
decoding drug
responsiveness
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Goal
Medications “tailor-made” for individuals
Medications adapted to each person’s own
genetic makeup
How “close” is this research to making
personalized medicine for most of us?
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Goal
(Eventually) Resulting in ...
Safer drugs (reduction of
side effects)
Increased drug effectiveness
Alternative drugs for
“standard treatments”
Dosages based on an
individual’s genetics
More effective and safer
vaccines
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Cytochrome p-450
enzymes
contribute to the metabolism
of ~ half of all medications
The Enzyme “Cytochrome P-450”
Examples of medicines ...
Erythromycin:
antibiotic used
Acetaminophen:
To
relieve
Codeine (opiate to treat pain or relieve
to treat
certain
infections
Diazepam:
To
relieve
mild
to
moderate
pain
from
cough)
caused
by
bacteria,
anxiety,
Cyclosporin
A: muscle
Ansuch as
headaches,
muscle
aches,
Acetaminophen bronchitis; diphtheria;
spasms,
and seizures
immunosuppressive
used with
menstrual periods,
coldsagent
and
Diazepam
(dye
az'
e
pam)
Legionnaires'
disease;
and
to control
agitation
recipients
of kidney,
liver,
bone
sore
throats, toothaches,
(whooping
cough);
Cyclosporin
Apertussis
caused
by
alcohol
marrow
and
backaches,
andpancreas
reactions
totransplants,
rheumatic
fever;
withdrawal)
andpneumonia;
it may
also
have
Erythromycin
vaccinations
(shots),
and
to clinical
venereal
(VD); and
application
in disease
the treatment
of
reduce
fever.
ear, intestine,
lung, urinary
autoimmune
disorders.
tract,
and
skin
infections.
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Example CYP3A4
Located 7q22
Super-family of cytochrome p-450
enzymes
Enzyme = Cytochrome P-450 3A4
Gene = CYP3A4
Expressed in the liver and intestines
(i.e., involved in detoxification)
3A4 is an essential enzyme
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Codeine Metabolism - 2D6
Located 22q13
2D6 is one enzyme that is required for the
metabolism of codeine to morphine
Most people are “extensive metabolizers”
that allows them to effectively metabolism
codeine to morphine
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Codeine Metabolism –
Balance of 3A4 and 2D6
You always have 3A4 .... but if the balance
of 3A4 is too high compared to 2D6, then
the bioavailability of codeine is reduced
If too much 3A4, codeine doesn’t
metabolize to morphine
3A4 converts “codeine” to “norcodeine”
which cannot be used by the body
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Codeine Metabolism – Balance of
3A4 and 2D6
3A4
2D6
converts ->
norcodeine
norcodeine is not used by the body
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Codeine Metabolism – Balance of
3A4 and 2D6
3A4
2D6
converts ->
morphine
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Factors affecting Metabolism or the Balance
of 2D6 and 3A4
Some medications that inhibit codeine
metabolism
.... like Quinidine (Quinidine Gluconate,
Quinidine Sulfate)
Medication that is used to correct
disturbances in the rhythm of the
heart (antiarrhythmic).
Also used to treat malaria
Quinidine inhibits 2D6
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Example of how other factors can affect the
balance of CYP3A4 and 2D6
Grapefruit juice before you take some
drugs can reduce your 3A4.
QUESTION: How does reducing 3A4 (i.e.,
in comparison the 2D6 is higher) affect
your ability to metabolize codeine?
ANS: you CAN convert the drug to
codeine (and subsequently to morphine)
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3A4
2D6
Grapefruit Juice
Quinidine
Group A
Group B
Grapefruit
Juice
Group C
Quinidine
Interactive Activity
Please form groups of 4 people each
Each group represents one human body
Each group (body) receives a stack of
cytochrome (CYP) cards
Distribute the cards equally
Your “body” is going to look for the CYP
enzymes
Interactive Activity
Dealing the enzymes
(proteins made by base pairs)
Based on the “summary”
(below) can the liver with
these enzymes convert
codeine into morphine?
2D6
Grapefruit
Juice
3A4
SUMMARY
Quinidine
More 2D6 than 3A4 = can convert
codeine into morphine
More 3A4 than 2D6 = cannot convert
codeine (makes norcodeine)
Grapefruit Juice = reduces 3A4
Quinidine = reduces 2D6
Alternative
Pharmacogenetics
Participant Interactive
Activity
Pharmacogenetics Case Study / Role Play
Please form groups of 3. Count off as
number 1, 2, or 3.
The number 1s are the patient, Frank
The number 2s are the nurse, Ms. Abby
The number 3s are the doctor, Dr.
Thomas.
Please read each situation in sequence.
When a “QUESTION” card appears, all 3
of you can work together (in your roles) to
try to answer the question.
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Case Study / Role Play: The situation
Frank had an abnormal cancer screening test. He came
to the clinic for a stereotactic biopsy. The nurse (Ms.
Abby) gave Frank a local anesthesia to reduce the
discomfort of the biopsy procedure. However, as Dr.
Thomas started to cut Frank to take a tissue sample for
the biopsy, Frank yelled that he wasn’t numb yet and to
stop. Ms. Abby showed Dr. Thomas what (medication)
had been given to Frank. It should have been sufficient
to numb his body for the biopsy. Frank continued to
complain about the pain.
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Case Study / Role Play: The situation
Frank next had his surgery and is in the recovery room
at the clinic. He is moaning and keeps asking Ms. Abby
for pain relief (codeine). She gave him an IV of the
codeine medication 30 minutes ago, but Frank is
complaining about the pain.
QUESTION: What are some reasons why Frank may
not be benefiting from the codeine (to relieve his pain)?
Dr. Thomas: Hummm, this should have had an effect on
you by now. Tell me Frank, how much alcohol do you
drink every day and what other drugs are you taking
daily?
Frank: Nothing. I haven’t had a drink for 10 years and I
don’t do drugs. Why are you asking me that?
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Case Study / Role Play: The situation
QUESTION: How may alcohol and other legal and
illegal drugs interact with codeine?
Dr. Thomas: Well alcohol and drugs can affect how you
respond to a painkiller. It can interfere with the
medication’s ability to reduce pain or it can interact with
the alcohol or drugs and make the patient overdose.
Ms. Abby: The question the doctor was asking doesn’t
only mean street drugs. Are you taking prescriptions that
aren’t in your medical record?
Frank: How would I know what’s in the medical record. I
get all of my care here. Wouldn’t everything be in there?
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Case Study / Role Play: The situation
Ms. Abby: Yes it should be in here. [Dr. Thomas goes
to the computer and both of them look at the medical
record]
Dr. Thomas: I don’t see anything that would interfere
with the painkillers working. These have codeine in
them. Now, we need for you to be honest with us… it
looks like you may have a very high tolerance for the
codeine … that maybe you do take some other drugs
that also have codeine. That is probably why you need
more. You have a high tolerance.
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Case Study / Role Play: The situation
Frank: Hey, I don’t do drugs. I told you. I’ve been
preparing for ceremony. I drink a lot of water and a lot of
juices. I am walking a lot so that I can be ready for
ceremony. I don’t do drugs.
Ms. Abby: I am looking at your medical record. It says
that you are taking quinidine because you have some
irregular heart rhythm.
Frank: Yeah, I do. So what?
Dr. Thomas: Quinidine can lower an enzyme (2D6) in
your body. If you have too little 2D6, your liver cannot
metabolize codeine into morphine.
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Case Study / Role Play: The situation
Frank: so are you saying I either have an irregular heart
beat or I have pain from surgery or procedures like
today?
Ms. Abby: Not quite. We are just trying to figure out a
way to help you. Do not quit taking your quinidine for
your heart rhythm. [She turns to Dr. Thomas] I wonder if
his 3A4 and 2D6 balance is off?
Frank: What the heck are you talking about? What does
that (3A4, 2D6) mean?
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Case Study / Role Play: The situation
Frank: so are you saying I either have an irregular heart
beat or I have pain from surgery or procedures like
today?
Ms. Abby: Not quite. We are just trying to figure out a
way to help you. Do not quit taking your quinidine for
your heart rhythm. [She turns to Dr. Thomas] I wonder if
his 3A4 and 2D6 balance is off?
Frank: What the heck are you talking about? What does
that (3A4, 2D6) mean?
QUESTION: What are 3A4 and 2D6?
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Case Study / Role Play: The situation
Ms. Abby: These are enzymes in your body. Everybody
has 3A4. We all need 3A4 to stay alive. But we also
have another enzyme, 2D6 that we need for certain
things to happen in our liver (our bodies). We need 2D6
to change codeine into morphine. There needs to be less
2D6 than 3A4 for your liver/body to be able to metabolize
or break down codeine into morphine. Morphine is why
most people experience pain relief.
Frank: So why not me?
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Case Study / Role Play: The situation
Ms. Abby (talking to Dr. Thomas): Do you remember
that other patient about 3 months ago who said she felt
everything and that the codeine wasn’t helping her at all?
We did another test to check the balance of 3A4 and
2D6 in her liver. She had too little 2D6 and her body
was metabolizing the codeine too quickly for her to
benefit from the codeine.
Dr. Thomas: Hummm. We are going to need to run
some tests.
Ms. Abby: Wait a minute. Frank, you said that you drink
a lot of juices as part of your preparation for ceremony.
What types of juices do you drink?
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Case Study / Role Play: The situation
Frank: I drink orange juice, cranberry and sometimes
grape juice … the unfermented type.
Dr. Thomas: But wait, Frank, do you also drink grapefruit
juice?
Frank: Not really. It’s rarely sold in our market out here
on the Rez.
Dr. Thomas: This could be a fairly simple fix. Actually, if
we can get you grapefruit juice, just 1-2 glasses a day,
that may be enough to gradually reduce the 3A4 enzyme
and would moderately elevate the 2D6. If you have
more of a balance between these 2 enzymes, you may
benefit from codeine as a painkiller.
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Case Study / Role Play: The situation
Frank: Well then, if a little is good, isn’t more better?
How about if I drink a whole bunch of grapefruit juice
then … like 6-8 glasses a day? Would that fix it so that
the codeine would work?
QUESTION: What is a likely outcome from Frank
drinking 6-8 glasses of grapefruit juice a day?
Ms. Abby: Well actually too much is just as bad as too
little. With too much, you would be like that other patient.
Too much grapefruit juice can reduce your 3A4 so that
you have way too much 2D6 … and then you metabolize
the medication too fast for your body to benefit from pain
relief.
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31
Case Study / Role Play: The situation
Frank: Fine, but what can you do to lessen the pain
now?
Dr. Thomas: We will give you another medication that
does not have codeine. It is not as good (effective) as
codeine, but should help reduce the discomfort.
Dr. Thomas: But I want to run those tests first. If there is
an imbalance of your 3A4 and 2D6, then the clinic will
provide you with 1-2 glasses of grapefruit juice … we
won’t know the appropriate amount until we run the
tests. It will take several weeks before your body is able
to change the balance between these enzymes so that
you can benefit from codeine drugs. We have another
procedure to do in 6 weeks that will go better if you can
benefit from the codeine.
Native
NativeAmerican
AmericanCancer
CancerInitiatives,
Initiatives,Incorporated
Incorporated(NACI)
(NACI)and
andMayo
MayoClinic’s
Clinic’s“Spirit
“SpiritofofEAGLES
EAGLESCommunity
CommunityNetwork
NetworkPrograms
Programs2”2”[P.I.
[P.I.Kaur;
Kaur;U54CA153605]
U54CA153605]
http:
http://www.NativeAmericanPrograms.org
NativeAmericanPrograms.org / http:///www.NatAmCancerInitiatives.org
/ http://www.NatAmCancerInitiatives.org
32
32
Case Study / Role Play: The situation
End Role play
QUESTION: What types of pharmacogenetics, other
than 3A4 and 2D6, are you aware of that are being used
in health care today?
QUESTION: If you could prioritize the types of drugs
that can be tailored to the individual AIAN patient, what
types of drugs would you like to see?
Native
NativeAmerican
AmericanCancer
CancerInitiatives,
Initiatives,Incorporated
Incorporated(NACI)
(NACI)and
andMayo
MayoClinic’s
Clinic’s“Spirit
“SpiritofofEAGLES
EAGLESCommunity
CommunityNetwork
NetworkPrograms
Programs2”2”[P.I.
[P.I.Kaur;
Kaur;U54CA153605]
U54CA153605]
http:
http://www.NativeAmericanPrograms.org
NativeAmericanPrograms.org / http:///www.NatAmCancerInitiatives.org
/ http://www.NatAmCancerInitiatives.org
33
33