pgx exam one cumulative Questions With Complete
Solutions
Define allele. Correct Answers Different variants of a gene
(e.g., CYP2C191 vs CYP2C192); wild-type is the most common
allele in a population.
Define haplotype. Correct Answers A set of alleles in a gene
that are usually inherited together (e.g., VKORC1 variants).
Define phenotype. Correct Answers An observable
characteristic (trait) in an organism or population (e.g., drug
response such as normal vs poor metabolizer).
Define polymorphism. Correct Answers Occurrence of different
variants of genes in the population. ≥1% frequency =
polymorphism (e.g., ABO blood types); <1% = mutation (often
disease-causing, e.g., sickle cell anemia).
How are CYP enzymes named? Correct Answers Root: CYP;
family number (>40% homology); subfamily letter (>55%
homology); gene number. Example: CYP2D6 = family 2,
subfamily D, gene 6.
How can SNPs affect proteins? Correct Answers Depending on
location, SNPs can alter protein structure/function (coding
region) or affect expression levels (promoter region).
How do CYP alterations affect non-prodrugs? Correct Answers
Gain-of-function → higher risk of therapeutic failure, lower
, toxicity risk. Loss-of-function → lower risk of therapeutic
failure, higher toxicity risk.
How do CYP alterations affect prodrugs? Correct Answers
Gain-of-function → lower risk of therapeutic failure, higher
toxicity risk. Loss-of-function → higher risk of therapeutic
failure, lower toxicity risk.
How do CYP polymorphisms affect active drugs vs prodrugs?
Correct Answers Active drugs: loss-of-function → ↑ drug levels
→ toxicity; gain-of-function → ↓ drug levels → reduced
efficacy. Prodrugs: loss-of-function → ↓ active metabolite →
therapeutic failure; gain-of-function → ↑ active metabolite →
toxicity.
How do CYP2B6 poor metabolizers impact efavirenz? Correct
Answers Genotypes like *6/*6 or *18/*18 cause high efavirenz
exposure, high risk of CNS toxicity.
How do CYP2C9 polymorphisms affect warfarin? Correct
Answers *2 and *3 alleles reduce metabolism of S-warfarin,
leading to higher plasma concentrations. PMs (*2/*2, *3/*3)
require lower doses.
How do reduced function CYP2C9 alleles impact drug
metabolism? Correct Answers Impaired clearance, increased
plasma concentration, higher risk of toxicity. Ethnic distribution:
*2, *3 common in Europeans; *8, *9, *11 in African descent.
How do VKORC1, CYP2C9, and CYP4F2 impact warfarin?
Correct Answers VKORC1: pharmacodynamics (target
Solutions
Define allele. Correct Answers Different variants of a gene
(e.g., CYP2C191 vs CYP2C192); wild-type is the most common
allele in a population.
Define haplotype. Correct Answers A set of alleles in a gene
that are usually inherited together (e.g., VKORC1 variants).
Define phenotype. Correct Answers An observable
characteristic (trait) in an organism or population (e.g., drug
response such as normal vs poor metabolizer).
Define polymorphism. Correct Answers Occurrence of different
variants of genes in the population. ≥1% frequency =
polymorphism (e.g., ABO blood types); <1% = mutation (often
disease-causing, e.g., sickle cell anemia).
How are CYP enzymes named? Correct Answers Root: CYP;
family number (>40% homology); subfamily letter (>55%
homology); gene number. Example: CYP2D6 = family 2,
subfamily D, gene 6.
How can SNPs affect proteins? Correct Answers Depending on
location, SNPs can alter protein structure/function (coding
region) or affect expression levels (promoter region).
How do CYP alterations affect non-prodrugs? Correct Answers
Gain-of-function → higher risk of therapeutic failure, lower
, toxicity risk. Loss-of-function → lower risk of therapeutic
failure, higher toxicity risk.
How do CYP alterations affect prodrugs? Correct Answers
Gain-of-function → lower risk of therapeutic failure, higher
toxicity risk. Loss-of-function → higher risk of therapeutic
failure, lower toxicity risk.
How do CYP polymorphisms affect active drugs vs prodrugs?
Correct Answers Active drugs: loss-of-function → ↑ drug levels
→ toxicity; gain-of-function → ↓ drug levels → reduced
efficacy. Prodrugs: loss-of-function → ↓ active metabolite →
therapeutic failure; gain-of-function → ↑ active metabolite →
toxicity.
How do CYP2B6 poor metabolizers impact efavirenz? Correct
Answers Genotypes like *6/*6 or *18/*18 cause high efavirenz
exposure, high risk of CNS toxicity.
How do CYP2C9 polymorphisms affect warfarin? Correct
Answers *2 and *3 alleles reduce metabolism of S-warfarin,
leading to higher plasma concentrations. PMs (*2/*2, *3/*3)
require lower doses.
How do reduced function CYP2C9 alleles impact drug
metabolism? Correct Answers Impaired clearance, increased
plasma concentration, higher risk of toxicity. Ethnic distribution:
*2, *3 common in Europeans; *8, *9, *11 in African descent.
How do VKORC1, CYP2C9, and CYP4F2 impact warfarin?
Correct Answers VKORC1: pharmacodynamics (target
