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Questions and Answers
What is the primary goal of pharmacogenetics in personalized medicine?
What is the primary goal of pharmacogenetics in personalized medicine?
- To analyze the biochemical pathways of disease progression
- To screen asymptomatic individuals for disease susceptibility
- To predict disease outcomes based on environmental factors
- To determine drug therapy based on genetic variations (correct)
Which of the following best describes the absorption phase of pharmacokinetics?
Which of the following best describes the absorption phase of pharmacokinetics?
- The drug is metabolized into active or inactive metabolites
- The drug is distributed to the target tissues after entering the bloodstream
- The drug enters the bloodstream typically through intestinal absorption (correct)
- The drug and its metabolites are eliminated from the body
In which phase of xenobiotic metabolism are lipophilic compounds converted to water-soluble products?
In which phase of xenobiotic metabolism are lipophilic compounds converted to water-soluble products?
- Excretion phase
- Phase I metabolism (correct)
- Distribution phase
- Phase II metabolism
What role does the Cytochrome P450 system play in liver function?
What role does the Cytochrome P450 system play in liver function?
Which statement accurately describes personalized medicine's approach to predicting disease severity?
Which statement accurately describes personalized medicine's approach to predicting disease severity?
Which enzyme is primarily responsible for the hydroxylation process during Phase I of drug metabolism?
Which enzyme is primarily responsible for the hydroxylation process during Phase I of drug metabolism?
What is the main consequence of having the CYP2C19 poor metabolizer allele in individuals of Asian or Pacific Islander descent?
What is the main consequence of having the CYP2C19 poor metabolizer allele in individuals of Asian or Pacific Islander descent?
In Phase II of drug metabolism, what is the primary role of the addition of a sugar or acetyl group to a hydroxyl group?
In Phase II of drug metabolism, what is the primary role of the addition of a sugar or acetyl group to a hydroxyl group?
What defines a polymorphism in the context of drug metabolism?
What defines a polymorphism in the context of drug metabolism?
How does the glucuronidation process function within drug metabolism?
How does the glucuronidation process function within drug metabolism?
What impact does being a slow acetylator have on drug metabolism?
What impact does being a slow acetylator have on drug metabolism?
Which of the following variants affects the metabolism of the anticoagulant warfarin?
Which of the following variants affects the metabolism of the anticoagulant warfarin?
What does the term 'ultrafast metabolizers' indicate in drug metabolism phenotypes?
What does the term 'ultrafast metabolizers' indicate in drug metabolism phenotypes?
What is the consequence of G6PD deficiency when exposed to oxidant drugs?
What is the consequence of G6PD deficiency when exposed to oxidant drugs?
Which enzyme is involved in the metabolic pathway for bilirubin excretion?
Which enzyme is involved in the metabolic pathway for bilirubin excretion?
Which of the following is NOT a way personalized medicine is used?
Which of the following is NOT a way personalized medicine is used?
Pharmacokinetics includes the processes of absorption, distribution, metabolism, and excretion.
Pharmacokinetics includes the processes of absorption, distribution, metabolism, and excretion.
What does the acronym ADME stand for in pharmacokinetics?
What does the acronym ADME stand for in pharmacokinetics?
The liver's role in metabolizing xenobiotics primarily involves the __________ system.
The liver's role in metabolizing xenobiotics primarily involves the __________ system.
Match the following liver functions with their descriptions:
Match the following liver functions with their descriptions:
What is the primary function of the enzyme cytochrome P450?
What is the primary function of the enzyme cytochrome P450?
Poor metabolizers are at risk for having toxic levels of drugs accumulate in their system.
Poor metabolizers are at risk for having toxic levels of drugs accumulate in their system.
What is the role of glucuronate transferase in drug metabolism?
What is the role of glucuronate transferase in drug metabolism?
Phase II drug metabolism involves the addition of a ______ group to the hydroxyl group from Phase I.
Phase II drug metabolism involves the addition of a ______ group to the hydroxyl group from Phase I.
Match the following cytochrome P450 variants with their effects on drug response:
Match the following cytochrome P450 variants with their effects on drug response:
What is a common result of being a slow acetylator?
What is a common result of being a slow acetylator?
The addition of glucuronic acid during Phase II does not aid in excreting substances.
The addition of glucuronic acid during Phase II does not aid in excreting substances.
What genetic variation affects the metabolism efficiency of warfarin in individuals?
What genetic variation affects the metabolism efficiency of warfarin in individuals?
G6PD deficiency can lead to ______ after exposure to oxidant drugs.
G6PD deficiency can lead to ______ after exposure to oxidant drugs.
The primary function of pharmacodynamics in pharmacogenetics involves:
The primary function of pharmacodynamics in pharmacogenetics involves:
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Study Notes
Personalized Medicine
- Definition: Tailors healthcare to individual patients based on genetic factors.
- Screening: Tests asymptomatic individuals for disease susceptibility.
- Pharmacogenetics: Matches drug therapy to individual genetic variations affecting drug metabolism and response.
- Disease Severity Prediction: Uses genetic polymorphisms to predict disease severity.
Pharmacokinetics
- Definition: Study of how the body absorbs, distributes, metabolizes, and excretes drugs (ADME).
- Absorption: Involves entry of the drug into the bloodstream, primarily through intestines.
- Distribution: Refers to the transport of the drug to the site of action.
- Metabolism: Breakdown of compounds into active or inactive metabolites.
- Excretion: Elimination of the drug and metabolites from the body.
Liver Function
- Key Roles:
- Intermediary metabolism and synthesis of plasma proteins.
- Metabolism of heme and bilirubin as well as purines and pyrimidines.
- Ethanol metabolism and production of VLDL, cholesterol, and bile.
- Involvement in xenobiotic metabolism via Cytochrome P450 enzymes.
Xenobiotics and Cytochrome P450
- Definition: Toxic compounds that the body can't efficiently degrade.
- Metabolism: Phase I converts lipophilic compounds to water-soluble forms; Phase II attaches functional groups for detoxification.
- Phase I Enzymes: Cytochrome P450 performs hydroxylation to increase water solubility.
Cytochrome P450 Family
- Characteristics: Large enzyme family with 56 genes; crucial for drug metabolism.
- Key Enzymes for Pharmacogenetics: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4.
Polymorphisms vs Mutations
- Polymorphism: Common population variations in DNA sequences.
- Mutation: Any deviation from normal DNA sequences.
Phase I Drug Metabolism Phenotypes
- Normal Metabolizers: Typical response to medications.
- Poor Metabolizers: Risk of drug toxicity due to accumulation.
- Ultrafast Metabolizers: Possible ineffectiveness of standard drug doses.
Ethnic Variations in Drug Response
- Example: Asian or Pacific Islanders may carry CYP2C19 poor metabolizer alleles, increasing toxicity risk when using specific antidepressants.
Phase II Drug Metabolism
- Glucuronidation: Addition of glucuronic acid to drugs for enhanced solubility; primarily mediated by glucuronate transferase in the liver.
N-Acetyltransferase Polymorphisms
- Impact on Drug Response:
- Slow Acetylators: Increased risk of drug toxicity.
- Fast Acetylators: May require higher doses for effective therapy.
Thiopurine Methyltransferase Polymorphisms
- Impact on Metabolism: Partial deficiency can improve drug effectiveness or increase toxicity based on dosage.
Pharmacodynamics
- Definition: Study of genetic influences on drug response through allelic variation in drug targets.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- Significance: Most common enzyme defect can lead to oxidative damage in red blood cells if exposed to oxidant drugs.
Case Study: Warfarin
- Purpose: Anticoagulant for thromboembolism prevention.
- Mechanism: Inhibits VKORC1 enzyme.
- Genetic Impact: CYP2C9 and VKORC1 polymorphisms influence drug metabolism and efficacy, affecting VKORC1 protein production.
Personalized Medicine
- Definition: Tailors healthcare to individual patients based on genetic factors.
- Screening: Tests asymptomatic individuals for disease susceptibility.
- Pharmacogenetics: Matches drug therapy to individual genetic variations affecting drug metabolism and response.
- Disease Severity Prediction: Uses genetic polymorphisms to predict disease severity.
Pharmacokinetics
- Definition: Study of how the body absorbs, distributes, metabolizes, and excretes drugs (ADME).
- Absorption: Involves entry of the drug into the bloodstream, primarily through intestines.
- Distribution: Refers to the transport of the drug to the site of action.
- Metabolism: Breakdown of compounds into active or inactive metabolites.
- Excretion: Elimination of the drug and metabolites from the body.
Liver Function
- Key Roles:
- Intermediary metabolism and synthesis of plasma proteins.
- Metabolism of heme and bilirubin as well as purines and pyrimidines.
- Ethanol metabolism and production of VLDL, cholesterol, and bile.
- Involvement in xenobiotic metabolism via Cytochrome P450 enzymes.
Xenobiotics and Cytochrome P450
- Definition: Toxic compounds that the body can't efficiently degrade.
- Metabolism: Phase I converts lipophilic compounds to water-soluble forms; Phase II attaches functional groups for detoxification.
- Phase I Enzymes: Cytochrome P450 performs hydroxylation to increase water solubility.
Cytochrome P450 Family
- Characteristics: Large enzyme family with 56 genes; crucial for drug metabolism.
- Key Enzymes for Pharmacogenetics: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4.
Polymorphisms vs Mutations
- Polymorphism: Common population variations in DNA sequences.
- Mutation: Any deviation from normal DNA sequences.
Phase I Drug Metabolism Phenotypes
- Normal Metabolizers: Typical response to medications.
- Poor Metabolizers: Risk of drug toxicity due to accumulation.
- Ultrafast Metabolizers: Possible ineffectiveness of standard drug doses.
Ethnic Variations in Drug Response
- Example: Asian or Pacific Islanders may carry CYP2C19 poor metabolizer alleles, increasing toxicity risk when using specific antidepressants.
Phase II Drug Metabolism
- Glucuronidation: Addition of glucuronic acid to drugs for enhanced solubility; primarily mediated by glucuronate transferase in the liver.
N-Acetyltransferase Polymorphisms
- Impact on Drug Response:
- Slow Acetylators: Increased risk of drug toxicity.
- Fast Acetylators: May require higher doses for effective therapy.
Thiopurine Methyltransferase Polymorphisms
- Impact on Metabolism: Partial deficiency can improve drug effectiveness or increase toxicity based on dosage.
Pharmacodynamics
- Definition: Study of genetic influences on drug response through allelic variation in drug targets.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- Significance: Most common enzyme defect can lead to oxidative damage in red blood cells if exposed to oxidant drugs.
Case Study: Warfarin
- Purpose: Anticoagulant for thromboembolism prevention.
- Mechanism: Inhibits VKORC1 enzyme.
- Genetic Impact: CYP2C9 and VKORC1 polymorphisms influence drug metabolism and efficacy, affecting VKORC1 protein production.
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