How to Better Understand the Results of Your Genetic Test

- Annette Youssef Pharm D. Candidate 2010

DRUG METABOLISM:

Drug Metabolism: refers to the rate (how rapidly or slowly) your body can change a drug from one form into another form

The cytochromes or CYPs are the metabolic factories in the liver and intestine

CYOCHROMES or CYPs

Different CYPs metabolize different drugs

There are several CYPsImportant CYPs that have different

genetic variations are CYP2C9, CYP2C19 and CYP2D6. They process about half of commonly prescribed medicines.

WHAT ARE ALLELES

An allele is one member of a pair or series of genes that occupy a specific position on a specific chromosome

Different combinations of alleles will produce a poor, intermediate, extensive (normal) or ultrarapid metabolizer

DRUG FORMS:

Drugs are designed in 2 forms:

1.) Active Drug Form: Drug is designed to work after it enters your body

2.) Prodrug (Inactive Drug Form): Drug will not work until it has been metabolized (must be changed to the active form)

GO TO NEXT SLIDE TO SEE HOW YOUR BODY REACTS TO THE DIFFERENT DRUG FORMS

ACTIVE DRUG VS. INACTIVE DRUG

Active Drug:

metabolism

Works in your body Ready to be removed from your body

Prodrug (Inactive Drug): metabolism metabolism

No effect in your body Works in your Ready to be removed body from your body

DRUG METABOLISM:

When you metabolize the 2 different versions of a drug (active form or inactive form) there are 2 different consequences:1.) Active Form: Your body changes the active

form of a drug into a form that makes it easier to remove from your body- generally an inactive form

2.) Inactive Form: Your body changes the inactive form into a form that works in your body

INTERPRETING YOUR RESULTS

You are now ready to interpret the results of your genetic test:

YOUR RESULTS

There are 4 possibilities for each gene that is tested: 1.) Poor Metabolizer of CYP2D6, CYP2C9,

CYP2C19 2.) Intermediate Metabolizer of CYP2D6, CYP2C9,

CYP2C19 3.) Extensive Metabolizer (Normal metabolizer) of

CYP2D6, CYP2C9, CYP2C19 4.) Ultra-rapid Metabolizer of CYP2D6

*Click on the metabolizer status that applies to you

WHAT ALLELES MAKE A POOR METABOLIZER

*1 is an allele with normal activity*2 is an allele with diminished activityYou inherit one allele from each of your

parentsIf you inherit *1/*1 you are a Normal

MetabolizerIf you inherit *2/*2  you are an Poor

Metabolizer

POOR METABOLIZER

Your cytochrome genes control the amount of cytochrome protein

If you are a poor metabolizer, your cytochromes have no or little cytochrome protein

POOR METABOLIZER

Poor Metabolizer:

Your body changes the drug to a different form very slowly or not at all (rate: 0-25% compared to normal)

How your body will react to:

1. Active Drug:

2. Prodrug (Inactive Drug):

POOR METABOLIZER + ACTIVE DRUG

Your body will not be able to, or will change the active drug to a form that is ready to be removed from your body very slowly: Result: The drug will stay in your body for a longer

period of time or you will have more drug reaching your system in a shorter period of time and levels of the active drug may be increased

Drug Effect: You will experience symptoms similar to overdosing on a drug

Go to next slide for example:

POOR METABOLIZER + ACTIVE DRUG: Example: Fictional drug “caffeinolam”

If you are taking a drug called “caffeinolam” and you are a poor metabolizer:

1.) You will experience the effects of caffeinolam for a longer period of time or your levels of caffeinolam will be higher than someone who is a normal metabolizer

2.) You may experience exaggerated effects of caffeinolam: such as a really rapid heart beat, extreme wakefulness, anxiety, sweating, etc.

ACTION:

Do not change your current therapy without talking to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy.

Your healthcare provider may tell you to decrease dose of drug Increase the time between doses (eg: take the

drug every other day instead of every day) Avoid the drug altogether

Back to Poor Metabolizer

Back to Results

POOR METABOLIZER + PRODRUG (INACTIVE DRUG)

Your body will not be able to, or will not change the inactive form of the drug to the active form of the drug at an extremely slow rate

Levels of the prodrug (inactive form) will be increased and the active form decreased Result: You will not experience the effects or the

benefits of the drug you are taking

Go to next slide for example:

POOR METABOLIZER + PRODRUG (INACTIVE DRUG): Example: Fictional Drug “teaolam”

If you are taking “teaolam” and you are a poor metabolizer, the active form of the drug is “teaozide”

Levels of “teaolam” will increase and levels of “teaozide” will be decreased or absent

You will not experience the effects of teaozide such as wakefulness and alertness

ACTION:

Do not change your current therapy without talking to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy

Back to Poor MetabolizerBack to Results

INTERMEDIATE METABOLIZER

Intermediate Metabolizer

Your body changes the drug to a different form at a slower rate than normal (~50% of that of normal metabolizers)

How your body will react to:

1. ) Active Drug:

2.) Prodrug (Inactive Drug):

WHAT ALLELES MAKE AN INTERMEDIATE METABOLIZER

*1 is an allele with normal activity*2 is an allele with diminished activityYou inherit one allele from each of your

parentsIf you inherit *1/*1 you are a Normal

MetabolizerIf you inherit *1/*2  you are an

Intermediate Metabolizer

INTERMEDIATE METABOLIZER + ACTIVE DRUG:

Your body will change the active drug to a form that is ready to be removed from your body at a rate that is half of that of a normal metabolizer: Result: The drug will stay in your body for an

extended period of time or you will have more drug reaching your system in a shorter period of time

Drug Effect: You may experience symptoms similar to a minor overdosage

Go to next slide for example:

INTERMEDIATE METABOLIZER + ACTIVE DRUG: Example Fictional Drug “caffeinolam”

If you are taking caffeinolam and you are an intermediate metabolizer:

1.) You will experience the effect of caffeinolam for a longer period of time: 4 hours vs. 2 hour if you metabolized caffeinolam normally

2.) You may experience toxic effects of caffeinolam: such as a really rapid heart beat, extreme wakefulness, anxiety, sweating, etc.

These would mimic the symptoms of an overdosage: having too much caffeinolam in a short period of time

ACTION:

Do not change your current therapy without talking to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy

They may tell you to: 1. Decrease dose of drug 2. Increase the time between doses (eg: take the

drug every other day instead of every day) 3. Avoid the drug altogether

Back to Intermediate MetabolizerBack to Results

INTERMEDIATE METABOLIZER + PRODRUG (INACTIVE DRUG):

Your body will change the inactive form of the drug to the active form of the drug at a slower rate than normal ~50%

Result: You will experience some of the benefits of drug therapy, but perhaps not maximally

Go to next slide for example:

INTERMEDIATE METABOLIZER + PRODRUG (INACTIVE DRUG): Fictional drug “teaolam”

If you are taking teaolam and you are an intermediate metabolizer:

Less of the active agent teaoside will be be available You will experience only some of the effects of

Teaolam such as alertness and wakefulness

ACTION:

To seek the benefits of drug therapy:Do not change your current therapy without talking

to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy They may tell you to: 1.) Increase the dose of the drug may be an option 2.) An alternative drug may be chosen that would

have an increased likelihood of workingBack to Intermediate MetabolizerBack to Results

EXTENSIVE METABOLIZER

Extensive Metabolizer

Your body metabolizes drug at a normal rate (not too fast and not to slow: just right)

WHAT ALLELES MAKE AN EXTENSIVE OR NORMAL METABOLIZER

*1 is an allele with normal activity*2 is an allele with diminished activityYou inherit one allele from each of your

parentsIf you inherit *1/*1 you are a Normal

Metabolizer

ACTION:

No changes to your drug regimen are warranted at this time

You represent the population that responds to drug therapy at the recommended doses

Back to Results

WHAT ALLELES MAKE AN ULTRARAPID METABOLIZER

*1 is an allele with normal activityYou inherit one allele from one parent

and more than one allele from another parent

If you inherit *1/*1 you are a Normal Metabolizer

If you inherit *1/*1 duplication you are an Ultrarapid Metabolizer

ULTRA RAPID METABOLIZER

Ultra Rapid Metabolizer

Your body changes the drug to the inactive form at a very rapid rate

How your body will react to:

1. Active Drug:

2. Prodrug (Inactive Drug):

ULTRA RAPID METABOLIZER + ACTIVE DRUG:

Your body will change the active drug to a form that is ready to be removed from your body at a very quick rate: Result: The drug will be removed from your body

very quickly and will have only a short time to exert its effects

Drug Effect: You may have a decreased response to your drug and its benefits

ULTRARAPID METABOLIZER + ACTIVE DRUG: Example Fictional Drug “caffeinolam”

If you are taking “caffeinolam” and you are an Ultrarapid metabolizer: 1.) You will experience the effect of Caffeinolam for

a shorter period of time: 1 hour vs. 3 hours if you metabolized coffee normally

2.) You will not experience the maximum effect of caffeinolam:

ACTION:

To seek benefits of drug therapy: Do not change your current therapy without talking

to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy Your provider may tell you to 1.) Increase the dose of the drug 2.) Decrease the dosing interval may be an option

(take the drug twice a day vs. once a day) 3.) An alternative drug may be chosen that would

have an increased likelihood of working

Back to Ultra Rapid MetabolizerBack to Results

ULTRA RAPID METABOLIZER + PRODRUG (INACTIVE DRUG):

Your body will change the inactive form of the drug to the active form at a very rapid rate

Result: There will be a greater amount of active drug in your body in a shorter period of time

Drug Effect: You will experience symptoms similar to overdosing on a drug

Go to next slide for example:

ULTRA RAPID METABOLIZER + PRODRUG (INACTIVE DRUG): Example Fictional Drug “caffeinolam”

If you are taking caffeinolam and you are an ultrarapid metabolizer:

1.) You will experience the effect of caffeinolam in a shorter period of time: 5 min. vs. 30 min if you metabolized caffeinolam normally

2.) You may experience toxic effects of caffeinolam: such as a really rapid heart beat, extreme wakefulness, anxiety, sweating, etc.

These would mimic the symptoms of an overdosage: having too much caffeinolam in a short period of time

ACTION:

Do not change your current therapy without talking to your healthcare provider first. They may have already taken your results into account as well as many other factors integral to your therapy 1. Decrease dose of drug 2. Increase the time between doses (eg: take the

drug every other day instead of every day) 3. Avoid the drug altogether

Back to Ultra Rapid MetabolizerBack to Results