Genomic Medicine and Personalized Treatment

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Questions and Answers

What is primarily responsible for phase I drug metabolism?

Thiopurine S methyl transferase

CYP450 enzymes (correct)

Glutathione S methyl transferase

Vitamin K epoxide reductase

What happens when a patient is a slow metabolizer of a drug?

Higher doses are needed to achieve therapeutic effects.

Drug detoxification occurs over a longer duration. (correct)

Drug detoxification occurs rapidly.

Side effects are less likely to occur.

Which drug requires a dose adjustment in patients with TPMT*3 variant?

Warfarin

Allopurinol

Citalopram

Thiopurines (correct)

Citalopram is metabolized by which enzyme?

CYP2D6 Signup and view all the answers

What increased risk does an individual face if their warfarin dose is too low?

Thrombosis Signup and view all the answers

Why is genetic testing important before prescribing warfarin?

To evaluate enzyme activity variants Signup and view all the answers

What effect does the VKORCI variant have on warfarin metabolism?

Reduces vitamin K synthesis Signup and view all the answers

What serious outcome is associated with allopurinol in individuals with HLA-B variant?

Steven-Johnson syndrome Signup and view all the answers

What does polymorphism in the gene encoding an enzyme affect in drug metabolism?

The rate of drug detoxification Signup and view all the answers

How does a diet rich in vitamin K affect warfarin treatment?

It may necessitate a dose reduction. Signup and view all the answers

What is the primary focus of pharmacogenetics?

Studying genomic variations affecting drug metabolism Signup and view all the answers

What term describes the application of pharmacogenetics in clinical management?

Personalized medicine Signup and view all the answers

Which of the following describes targeted therapy?

Utilizing monoclonal antibody therapy to target specific mutations Signup and view all the answers

Which gene is identified as a proto-oncogene that encodes a receptor tyrosine kinase?

KIT Signup and view all the answers

Imatinib is effective for treating which of the following conditions?

Gastrointestinal stromal tumors with c-KIT driver mutations Signup and view all the answers

What two main groups of genes are tested in personalized medicine?

Genes for drug absorption and drug action Signup and view all the answers

Where are most enzymatic reactions related to drug metabolism primarily found?

Liver Signup and view all the answers

Which inheritance pattern is most common for the genes encoding enzymes used in drug metabolism?

Autosomal recessive inheritance Signup and view all the answers

Signup and view all the answers

Study Notes

Genomic Medicine and Personalized Treatment

Genomic medicine studies how gene variations affect drug metabolism, predicting responses, minimizing side effects, enhancing treatment efficiency.
Pharmacogenetics analyzes specific gene variants, while pharmacogenomics examines entire genome SNPs.
Personalized/precision medicine applies pharmacogenetic findings to individual treatment plans.
Lifestyle, diet, and environmental factors influence treatment effectiveness.

Targeted Therapy

Targeted therapy uses monoclonal antibodies to target specific molecules in altered signal pathways of cancers.
Trastuzumab (Herceptin) targets HER2neu gene amplification in breast cancer.
Imatinib (Gleevec) targets receptor tyrosine kinases (e.g., c-KIT) for treatment of gastrointestinal stromal tumors (GIST) with c-KIT driver mutations and Philadelphia positive chronic myeloid leukemia.

Pharmacogenetic Testing

Personalized medicine tests for genes impacting drug absorption, distribution, metabolism, and excretion (pharmacokinetics) and those related to drug action (pharmacodynamics).
Genetic information controls all individual traits and affects both endogenous and exogenous (drug) metabolism.
Most enzymatic reactions occur in the liver and genes for these enzymes are usually inherited in an autosomal recessive pattern.

Drug Metabolism and Pharmacokinetics

Drugs undergo phase I metabolism (minor structural changes like removing functional groups, mainly cytochrome enzymes like CYP450) and phase II metabolism (complex enzymatic reactions, e.g., glutathione S-methyltransferase).
Slow metabolizers have enzymes that detoxify drugs slower (reduced dosage needed), while rapid metabolizers have faster detoxification (increased dosage needed). Gene variations (SNPs) cause these differences.

Examples of Pharmacogenetics in Clinical Practice

Thiopurines: Used to treat leukemia, metabolized by thiopurine S-methyltransferase (TPMT). TPMT*3 variant significantly reduces enzyme activity (lower dose needed; reduced dosage to 1/10).
Citalopram: Antidepressant metabolized by CYP2D6. Variants like CYP2D6*9, #10, and #41 affect enzyme activity (adjust dose accordingly for reduced or increased function).
Warfarin: Used for hypercoagulability, metabolized by CYP2C9. Certain CYP2C9 variants (e.g., *3, *2) severely reduce enzyme activity (warfarin levels carefully monitored). Warfarin inhibits vitamin K epoxide reductase (VKORCI); variants in this enzyme also influence treatment dosage to prevent bleeding. Vitamin K rich diet is a consideration for patients on Warfarin therapy.
Allopurinol: Used for gout. HLA-B variants increase risk of severe Stevens-Johnson syndrome (genetic testing recommended).

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Description

Explore the cutting-edge field of genomic medicine and how it tailors treatments based on individual genetic profiles. This quiz covers topics such as pharmacogenetics, targeted therapy, and the influence of lifestyle on treatment efficacy. Test your understanding of how personalized medicine can revolutionize patient care.