GN 1.5.2 Flashcards
Define pharmacogenomics.
Development of NEW DRUGS based on INCREASING KNOWLEDGE of all genes in the human genome
What was the lesson the three patients treated with the same drug dosage (antileukemia, antihypertensive, oral anticoagulant)?
The three levels of effect (hyperactive, desired response, and hypoactive)
What the four major cytochromes involved in drug metabolism?
CYP3A4, CYP2D6, CYP2C19, CYP2C9
For a drug to be effective, a drug or toxicant must: (4 pharmacokinetic principles)
1) Reach target
2) Be in active form
3) Sufficient Concentration
4) Sufficient period of time
In pharmacology, what are the three desires for the clinical decision?
Right drug, right dose, right patient
In regards to metabolism of debrisoquine, most humans are? Less are? The least are?
Most: Extensive metabolizers
Less: Poor metabolizers (hint: LOF mutations more prevalent)
Least: Hyperactive metabolizers (GOF mutations rare)
What are the two main studies of pharmacology?
Pharmacokinetics and pharmacodynamics
What is significant about primiquine?
In the 1940s, AA soldiers had a different response to the drug than white soldiers (1st observed racial inheritance of drug-related metabolism)
What is the process by which an environmental influence can increase/decrease the expression of drug metabolizing enzymes?
Induction
In the FDA table of pharmacogenomic biomarkers of drug labels, there are 160 issues listed w/ 74 coming from drug metabolizing enzymes. Many of the drug metabolizing polymorphisms occur in what family of enzymes?
CYP
Where are the CYPs most active?
Liver
Increasing expression of drug metabolizing enzymes leads to what result on concentration of the drug?
Decrease concentration, faster elimination
What is pharmacokinetics?
What patient does to the drug (dose leading to amount of drug at active site)
What is a haplotype?
A haplotype is a group of genes within an organism that was inherited together from a single parent
Why in Brazil (and increasingly more places around the world) is ethnicity no longer a good predictor of genetic predispositions?
Lack of Population Isolation
The antihypertensive medication, debrisoquine, is metabolized by what CYP?
CYP2D6
What is pharmacodynamics
What the drug does to the patient (the effects/mechanism of the drug)
Define pharmacogenetics.
Study of heritability in drug responses
In the case of the patient taking erythromycin in addition to terfenidine, why is the metabolism of terfenidine effected?
In this specific case, erythromycin inhibits CYP3A4 that is used to metabolize terfenidine.
Drugs can compete for/inhibit drug metabolizing enzymes
What super family of membrane bound proteins plays a key role in drug metabolism?
CYP family
Getting the right form to the right place in right amount. Requires the balance of what 4 biological mechanisms.
A - Absorption
D - Distribution
M - Metabolism
E - Excretion
What is the expression of most variants of CYP2D6?
Diminished or no activity
