Flashcards in Unit 1 - Pharmacogenetics and Pharmacogenomics Deck (14):
difference between pharmacogenetics and pharmacogenomics
genetics: study of genes and their alleles in relationship to drug response in a given patient
genomics: study of genes related to drug metabolism, and use of knowledge to develop new, targeting drugs
some facts on adverse drug reactions?
ADR; toxic reactions to rugs are well known
-ADRs are 4th/5th leading cause of death among adults
-overall incidence in US hospitals is 6.7%, fatalities 0.3%
--over 2 million serious ADRs to FDA approved drugs each year
-50% of all ADRs are due to genetic anomalies
pharmacokinetics VS pharmacodynamics
kinetics: study of time course of drug metabolism, absorption, transport, excretion
dynamics: how drug affects body
-relationship between drug, target, and related receptors/enzymes
what are the 6 major cytochrome p450 enzymes that metabolize 90% of drugs?
CYP1A1, 1A2, 2D9, 2D6, 2C19, and 3A4
what are the data on CYP2D6? what happens to activity if this gene is spliced, framshifted, missense, or copy number variant?
-involved in metabolism of ~100 drugs
--antidepressants, neuroleptics, beta-blockers, analgesics
-spliced or frameshift: no activity
-missense: decreased activity
-copy number variant: increased activity
what happens if poor or ultra metabolizers are given codeine?
codeine is a prodrug that is converted to active morphine by CYP2D6
-poor metabolizers cannot convert drug, and have limited therapeutic effect
-ultra metabolizers may become intoxicated with even low doses of codeine
what does TPMT do?
thiopurine methyltransferase gene that catalyzes s-methylation and inactivates 6-MP and 6-thioguanine
X-linked disease that is susceptible to drug-induced hemolysis
-rare in Caucasians, but 10% of Africans and common in Mediterranean
-oxidant drugs deplete cell of reduced glutathione, resulting in oxidative damage and hemolysis
can G6PD deficient people still take oxidant drugs?
can take them for a short time, but longer exposure causes jaundice, hemolysis, and possibly death
hemolytic anemia caused by ingesting fava beans
-extreme form of G6PD, but not all people with G6PD are affected by fava beans
explain malignant hyperthermia
AD disease with mutations in 6 loci (RYR1, CACNL 1A3, 4 more)
-negative response to inhalation anesthetics (high fever, dustained contractions, hypercatabolism) due to elevation of ionized Ca in the muscle
--easy to undo if caught early enough
-can be diagnosed by muscle biopsy and muscle contracture testing
how does coumadin work?
inhibits the enzyme epoxide reductase (Vit K reductase, VKOR)
-this inhibits reduced vit K formation, which is essential for clotting
explain the pharmacokinetics of warfarin?
there are 2 alleles that are important
1. VKORC1 allele of VKOR gene
-30% of variation
-low dose (more sensitive to drug; Asians)
-high dose (more resistant to drug; Africans)
2. CYP2C9 allele of cytochrome p450
-common in Caucasians, rare in others