Pharmacogenetics Flashcards
Drug Response Phenotypes
Differences in:
- Metabolism
- Transport
- Drug Target
Type of genetic variation
- Copy number variation
- Indel
- Single nucleotide polymorphism (SNP)
Genetic variations in metabolism lead to
- Changes in bioavailability and/or clearance
- Can result in differences in response and/or toxicity
Genetic variations in transport lead to
- Changes in bioavailability, biliary or renal elimination
- Changes in drug distribution and tissue uptake
- changes in response and/or toxicity
Genetic variations in drug target lead to
Changes in concentration-response relationship
Types of genetic variation
- Duplications/copy number variations (CNV)
- Indels
- Single nucleotide substitutions (SNPs)
Duplications/copy number variations (CNV)
increase or decrease in function
Indels
- usually decreased function, often frameshift
insertions and deletions
genetic mutations that involve the insertion or deletion of one or more nucleotides (the building blocks of DNA) in a DNA sequence. These mutations can have significant effects on genes and their functions.
Single nucleotide substitutions (SNPs)
usually decreased function (if any); most common variation
Missense mutation
SNP causes amino acid substitution
Nonsense mutation
SNP causes a premature stop codon, leading to a shortened, and likely nonfunctional, protein
Silent mutation
SNP has no effect on amino acid
Pharmacogenomics
you’re looking at the genetic material as a whole and how it affects drug’s response
Pharmacogenetics
you’re taking into consideration only one gene and how it effects the response to drugs
Deletion of an entire gene which encodes for CYP2D6
- Metabolism
- CNV
A change which results in a premature stop codon, leading to a nonfunctional OATP1B1
- transport
- SNP
A duplication of a gene which results in a high-functioning beta-adrenergic receptor
- drug target
- CNV
An insertion which results in a frameshift of the gene that encodes for CYP2C9
- metabolism
- indel
A mutation in a gene for OCT1 which results in one amino acid change from pro → lys
- transport
- SNP
Deletion of an entire gene which
encodes for CYP3A4
CL, F, Efficacy, Toxicity
- Decrease clearance
- Increase Bioavailability
- Increase Efficacy
- Increase Toxicity
Duplication of a gene which leads to an increased expression of the P-gp transporter
- Increase Clearance
- Decrease Bioavailability
- Decrease Efficacy
- Decrease Toxicity
A mutation which renders the insulin receptor inactive
- No effect on Clearance
- No effect on Bioavailability
- Decrease Efficacy
- No effect on Toxicity
Why are Pgx data important for pharmacists?
We need to consider ancestral genetic variations in drug dosing recommendations
Explain to a health professional how CPIC guidelines could be applied to drug therapy decisions
- Clinicians would receive a patient’s genetic variability report whenever a drug needs to be ordered in order to be made aware and get ahead of efficacy/toxicity issues.
- The guidelines try to have clinicians understand HOW available genetic test results should be used to optimize drug therapy, NOT WHETHER tests should be ordered.
- The goal is to teach clinicians how to use a patient’s genotype to optimize drug therapy.
