2 Flashcards
Codeine
● Metabolized into morphine by CYP2D6
● Morphine is an opioid, provides pain relief
● However, opioid toxicity can lead to respiratory depression and death
Codeine Metabolism
Codeine —> CYP2D6 —> Morphine
Codeine is INACTIVE FORM
Morphine is ACTIVE FORM
CYP2D6 PK
Pharmacogenomic Impact
-FDA BBW
-Avoid use of codeine in breastfeeding women
-Genomic testing available (not required)
-Avoid codeine in children <12
CPIC rec. avoiding codeine in UM and PM
-UM = risk of AE
-PM = lack of efficacy
-Avoid other opioids (that met. by CYP2D6) in UM
-like tramadol, hydrocodone, oxycodone
If poor metabolizer for codeine, then…
probably poor metabolizer for other opioids (2D6)
find other pain relief meds NOT met. by 2D6
In theory, which metabolizer status should have the highest codeine AUC or Cmax?
Poor metabolizer
Alternatively, which metabolizer status should have the highest morphine AUC/Cmax
Ultra metabolizer
CYP2D6 UMs may experience more
analgesia/pain relief
CYP2D6 PMs may experience
hypo analgesia or lack of pain relief
Which opioids to RECOMMEND (that are not met by cyp2D6)?
Hydromorphone!
Morphine, yes if low dose/monitoring, no based on infant death study
Mu opioid receptor, gene of interest
(OPRM1)
Variant: OPRM1 118A>G (rs1799971)
-non syn SNP: A changing to G
-results in AA change from asparagine to aspartate (NON SYN SNP)
Population prevalence
-10-15% Caucasian
-50% Asian
Mu Pharmacokinetics
Higher opioid dosing requirements have been reported with AG and GG variant genotypes (but small extent)
-AA and AG also experienced less side effects (RD)
Morphine metabolized by…
UGT2B7
M3G (major), does not cross BBB, no analgesic effect, can cause allogydia, seizures
M6G (minor), crosses BBB, weak analgesic effect
UGT2B7
