Pharmacogenetics Flashcards
What is one of the leading causes of hospitalization and death in the US?
Adverse drug reactions
What term can be used to describe current pharmacologic practice?
“One size fits all” > based on the “average” patient
What is the role of G6PD in the body?
Supplies NADPH and glutathione in RBC’s
What is the nature of a G6PD deficiency mutation and what are the most common types?
Mutation is sex-linked and carried on X chromosome; SNPs
What is the main difference between pharmacogenetics and pharmacogenomics?
Pharmacogenetics focuses on a single gene and pharmacogenomics focuses on a multi gene approach
What are most drugs metabolized by?
A Cyp450 subtype
What are SNPs?
Small nucleotide changes, most common polymorphism
What are chromosomal insertions or deletions and what do they cause?
That are large sequence changes and can cause frameshift mutations
What is a frameshift mutation?
Insertion or deletion that alters the reading frame of a gene
What is a missense mutation?
Substitution that results in a different amino acid
What is a nonsense mutation?
Substitution that results in a stop codon
What is a silent mutation?
Substitution that results in no significant effects
What is an in-frame deletion or insertion?
Deletion or insertion of 3 nucleotides that introduces or removes an amino acid into the protein, but does not alter the reading frame
What is a neutral mutation?
Changes in amino acid sequence of a protein without altering its ability to function
What is a loss of function mutation?
Causes a complete or partial loss of a function of the protein
What is a gain of function mutation?
Causes over-activity of the protein or the appearance of a new trait or function
What causes over 90% of human genetic variation?
SNPs
What is personalized medicine?
Identifying all the SNPs in patients before prescribing them drugs.
-Allows researches to study all alleles to see if there will be adverse effects
What are the important proteins and genes involved in drug metabolism
G6PD, 2D6, and NAT2
Most mutations can be categorized in two areas. What are they?
1) Changes in gene copy number
2) changes in function of protein
What does a change in gene copy number result in?
Gene duplications, nonsense mutations, and gene deletion (Loss of function mutations)
What enzyme is associated with metabolism of the drugs Debrisoquin, Codeine, and Nortripyline?
Cyp2D6
What drugs does NAT2 metabolize?
Hydralazine, Isoniazid, and pracainamide (HIP drugs)
How does NAT2 change protein function?
Transfers and acetyl group from acetyl CoA to the acceptor amine, resulting in formation of an amide on the drug
