Week 5

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Questions and Answers

What do genetic polymorphisms in Phase I enzymes result in?

Altered drug efficacy and safety

Patients who biotransform many drugs at different rates (correct)

Increased enzyme activity for all drugs

Universal drug response among all patients

What drug does the CYP 2D6 enzyme convert codeine into?

Heroin

Morphine (correct)

Oxycodone

Fentanyl

What is codeine?

An opioid analgesic

A stimulant

An anti-inflammatory drug

A prodrug (correct)

What is the most common form of genetic polymorphism?

Wild type Signup and view all the answers

Which polymorphisms receive the least benefit from codeine?

PMs and IMs Signup and view all the answers

Is Thiopurine-S-methyltransferase (TPMT) a Phase I or Phase II enzyme?

Phase II Signup and view all the answers

What drugs does Thiopurine-S-methyltransferase (TPMT) deactivate?

Thiopurine drugs Signup and view all the answers

Which of the following is a thiopurine drug used to suppress the immune system that may result in bone marrow suppression and loss of blood cell production?

Azathioprine Signup and view all the answers

What percentage of Europeans are intermediate metabolizers (IMs) for TPMT?

10-15% Signup and view all the answers

What percentage of Europeans have low to no TPMT activity?

0.3-1% Signup and view all the answers

What should be done when someone is an intermediate metabolizer (IM) for thiopurine methyltransferase (TPMT)?

Lower the dose Signup and view all the answers

What can happen to patients who have low or no TPMT activity?

They cannot deactivate thiopurine drugs and can die Signup and view all the answers

Match each enzyme/ system to its associated drug

Glucose-6-Phosphate Dehydrogenase (G6PD) = Sulfamethoxazole Acetylcholinesterase (AchE) = Succinylcholine HLA Histocompability Complex = Abacavir Vitamin K Expoxidase Reductase = Warfarin Signup and view all the answers

What can sulfamethoxazole cause in people who have decreased G6P?

Hemolysis Signup and view all the answers

Why can succinylcholine be problematic?

When a patient has a genetic polymorphism in their AchE Signup and view all the answers

Why does abacavir cause adverse drug reactions in HIV patients?

Polymorphisms in the human HLA histocompatibility complex Signup and view all the answers

For which drug were ADRs considered idiosyncratic before further discoveries?

Abacavir Signup and view all the answers

What is the role of Vitamin K Epoxidase reductase (VKORC1)?

The clotting system is retarded and the ability to form a clot is reduced. Signup and view all the answers

What happens with a polymorphism in Vitamin K Epoxidase reductase (VKORC1)?

Makes the patient supersensitive to the inhibition by warfarin. Much lower doses, or alternative anticoagulants, required to prevent harmful bleeding Signup and view all the answers

Study Notes

Genetic Polymorphisms in Phase I Enzymes

Genetic polymorphisms in Phase I enzymes can result in altered drug metabolism, leading to variations in drug efficacy and adverse drug reactions (ADRs).

CYP 2D6 Enzyme

The CYP 2D6 enzyme converts codeine into morphine.
Codeine is an opioid analgesic often used for pain relief.

Common Forms of Genetic Polymorphism

The most common form of genetic polymorphism is single nucleotide polymorphisms (SNPs).

Polymorphisms and Codeine Benefit

Individuals with certain polymorphisms in CYP2D6 may receive less benefit from codeine.

Thiopurine-S-methyltransferase (TPMT)

Thiopurine-S-methyltransferase (TPMT) is a Phase II enzyme involved in the detoxification of thiopurine drugs.
TPMT deactivates thiopurine drugs like azathioprine and 6-mercaptopurine.

Thiopurine Drugs

Azathioprine is a thiopurine drug used to suppress the immune system.
Azathioprine may cause bone marrow suppression and loss of blood cell production.

Intermediate Metabolizers (IMs) for TPMT

Approximately 10% of Europeans are intermediate metabolizers (IMs) for TPMT.
About 0.3% of Europeans have low to no TPMT activity.

TPMT Intermediate Metabolizer Recommendations

Individuals who are intermediate metabolizers (IMs) for thiopurine methyltransferase (TPMT) require reduced doses of thiopurine drugs to prevent toxicity.

TPMT Deficiency

Individuals with low or no TPMT activity may experience severe toxicity from thiopurine drugs.

Enzyme/System and Associated Drug Matches

CYP2D6 - codeine
TPMT - azathioprine
Glucose-6-Phosphate Dehydrogenase (G6PD) - sulfamethoxazole
Butyrylcholinesterase - succinylcholine
HLA-B*5701 - abacavir
Vitamin K Epoxidase Reductase (VKORC1) - warfarin

Adverse Drug Reactions (ADRs)

Sulfamethoxazole can cause hemolytic anemia in individuals with decreased G6PD activity.
Succinylcholine can cause prolonged muscle paralysis in individuals with genetic variations in butyrylcholinesterase.
Abacavir causes adverse drug reactions in HIV patients with the HLA-B*5701 gene.
ADRs associated with abacavir were initially considered idiosyncratic before further discoveries.

Vitamin K Epoxidase Reductase (VKORC1)

Vitamin K Epoxidase reductase (VKORC1) plays a key role in the metabolism of warfarin.
Polymorphisms in VKORC1 can lead to variations in warfarin responsiveness, necessitating precise dose adjustments.

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Description

Explore the implications of genetic polymorphisms in Phase I enzymes and how they affect drug metabolism, efficacy, and toxicity. This quiz delves into the influence of these genetic variations on individual responses to pharmacotherapy. Test your knowledge on this critical aspect of pharmacogenomics.