Calculations, EBP & Pharmacogenomics Flashcards
1 inch
2.54 cm
1 tsp –> ml
5 ml
1000 mcg –> mg
1 mg
1:20
1 g of solute in 20 ml of solution
0.02%
0.02g in 100 ml
1 kg
2.2 lbs
1 lb –> oz
16 oz
1 tbsp –> tsp
3 tsp
1 oz –> ml
30 ml
3 principles of EBM
make decisions from the best available evidence
not all evidence is equal
evidence alone is never enough
3 components of EBP decision making
evidence
circumstances
values
within context
evidence-based approach to medication questions
- define the question (PICO)
- systematically search for relevant info
- critically evaluate the literature
- apply findings to patient/case/question
pharmacogenetics
study of how genetic differences in a SINGLE gene influence variability in drug response (ex efficacy and toxicity
ex. B1-adrenergic receptors on carvedilol
pharmacogenomics
study of how genetic differences in MULTIPLE genes influence variability in drug response (ex efficacy and toxicity)
ex B1 and B2 a2-adrenergic receptors and CYP2D6 on carvedilol
gene
series of codons that forms a protein
allele
sequence of nucleic acid bases at a given gene chromosomal locus
homozygous genotype
two identical alleles
heterozygous genotype
two different alleles
phenotype
outward expression of genotype
mutation
alteration in DNA code occuring <1% of time in the population
polymorphisms
alterations in the DNA code occuring >1% of the time in the population
single-nucleotide polymorphism (SNP)
single base pair difference in DNA occurring on every chromosome
what phase of metabolism is CYP 450?
phase I
examples of drugs metabolized by CYP2D6
codeine
nortriptyline
tamoxifen
codeine w CYP2D6 metabolism
codeine is a prodrug!
poor metabolism - no pain relief but AEs
ultrarapid metabolism - pain control with AEs
nortriptylene w CYP2D6 metabolism
nortriptylene is an active drug!
poor metabolism - depression relief w/ adverse effects
ultrarapid - no depression relief, no AEs
tamoxifen w CYP2D6 metabolism
poor metabolism - deceased efficacy, increased risk of cancer recurrence
CYP2D6 inhibitors
SSRIs prozac, paxil, zoloft - these should all be avoided w tamoxifen due to risk of recurrence!!!
examples of drugs metabolized by CPY2D19
omeprazole - & all PPIs
clopidogrel
omeprazole w CPY2C19 metabolism
rapid and intermediate metabolizers have decreased ulcer cure rates
clopidogrel w CYP2C19 metabolism
clopidogrel is a prodrug!
poor or intermediate metabolizers have poor efficacy –> recommend other platelet inhibitors (ticagrelor or prasugrel)
CYP2C19 inhibitors
proton pump inhibitors
decreased efficacy of clopidogrel -> not converted to active drug -> risk for clotting
avoid omeprazole and clopidogrel! prefer H2 antagonists/antacids (famotidine)
examples of drugs metabolized by DPD
5-FU
cepecitabine
tegafur
(chemotherapy drugs)
DPD deficiency results in
decreased efficacy of chemotherapy agents & risk for toxicities
severe AEs! ex. myelosuppression, mucositis, neurotoxicity, hand-and-foot syndrome, diarrhea
example of drug metabolized by UGT 1A1
ironetecan - tx for colon cancer
AEs with irenotecan UGT1A1 metabolism
diarrhea
neutropenia
examples of drugs metabolized by thiopurine S-Methyltransferase (TPMT)
azathioprine
6-MP
6- thioguanine
anticancer/immunologics
G6PD deficiency causes
excessive hemolysis of RBCs
example of drugs metabolized by G6PD
carbamazepine
ribavirin
carbamazepine w G6PD deficiency
risk of stevens johnsons syndrome and TEN
why do we need to be cautious with warfarin?
narrow therapeutic range due to CYP2C9 and VKORC1
what resource provides authoritative info regarding drugs for breastfeeding?
lactmed
what resource provides comprehensive information regarding drug use during pregnancy and lactation?
Brigg’s
what is an authoritative reference for antibiotic prescribing and dosing?
john hopkins abx guide
