Pharmacology - Pharmacogenomics (Exam 1) Flashcards
N-acetyltransferase 2 catalyzes the ___________ of numerous aromatic amine and hydrazine drugs
N-acetylation
In N-acetylation polymorphism (N-acetyltransferase 2), what are slow acetylators predisposed to?
-peripheral neuropathy
-drug induced SLE
-urinary bladder cancer
In N-acetylation polymorphism (N-acetyltransferase 2), what are rapid acetylators predisposed to?
-myelosuppression
-colorectal cancer
What can help infer treatment outcomes?
ethnicity
Thiopurine-S-Methyltransferase (TMPT) catalyzes the __________ of anticancer and anti-inflammatory drugs
deactivation
What does a defect in Thiopurine-S-Methyltransferase (TMPT) cause after following standard doses of these drugs?
severe hematapoietic toxicity
Uridine Diphosphate Glucuronosyltransferase (UGT) catalyzes the _________ of bilirubin, various drugs, and xenobiotics
glucuronidation
What does a deficiency in UGT1A1-catalyzed bilirubin glucuronidation associated with 7 TA repeats in the promoter result in?
Gilbert’s syndrome
What is Uridine Diphosphate Glucuronosyltransferase (UGT) polymorphism associated with?
increased toxicity (myelosuppression and diarrhea)
CYP2D6 is a form of cytochrome P450 and it is important in the ________ of a wide variety of drugs
oxidation
In CYP2D6 oxidation polymorphism, poor metabolizers yield an _________ of the parent drug for a wide variety of drugs like beta blockers, antiarrhythmics, antidepressants, and neuroleptics
accumulation
In CYP2D6 oxidation polymorphism, the __________ and ________ of drugs metabolized to CYP2D6 substrates may also be affected
efficacy; toxicity
In CYP2D6 oxidation polymorphism, poor metabolizers may be less sensitive to drugs that depend upon CYP2D6 to produce pharmacologically active metabolites, leading to ________ __________
therapeutic failure
In CYP2D6 oxidation polymorphism, ultrarapid metabolizers may be _________ sensitive to toxic effects of metabolites produced via CYP2D6
more
CYP2C9 catalyzes the oxidation of the anticoagulant ________, as well as other drugs including phenytoin, tolbutamide, and losartan
warfarin
People who are homozygous for certain variant CYP2C9 alleles exhibit _______ reduction in Warfarin clearance, resulting in _________ complications
90%; bleeding
CYP2C19 catalyzes the oxidation of __________, ____________, and ____________
clopidogrel; proton pump inhibitors; SSRIs
In CYP2C19 oxidation polymorphism, poor metabolizers are at a high risk of __________ ________ due to insufficient levels of active metabolite. Therefore, they are at increased risk of heart attack, stroke, death, etc. due to Clopidogrel not working properly.
treatment failure
Genetic trait defined by DNA sequences inherited from Mom and Dad (can be homozygous or heterozygous)
genotype
A biologic or measurable expression of the genetic trait that is dependent upon the level of penetrance of the gene, the accuracy and selectivity of the method used to measure it, and the influence of environmental factors in the expression of the trait
phenotype
Single letter is changed to a different letter
single nucleotide polymorphisms (SNPs)
Sometimes, the function of a gene is not affected unless there are multiple changes all present within the gene. Scientists can group these changes together and give it a specific name or number
haplotype
Beta-1 and beta-2 receptor polymorphisms have been shown to affect therapeutic response to beta-2 receptor ________ and _______.
This is the basis for treatment failure of beta-2 receptor therapy in patients with heart failure
agonists; antagonists
What is another example of drug target (receptor) polymorphisms?
antipsychotic drugs
(not widely studied, but different patients have different responses)
What do transport proteins influence?
absorption
distribution
excretion
Hepatic uptake and elimination of statin drugs are facilitated by the solute carrier transporter family _______
1B1
Changes in function of SLCO1B1 transporter can increase _________ concentration of statins and severity of statin-related muscle damage
plasma
A polymorphism in SLCO1B1 increases systemic
muscle toxicity
