I'm going to pull selections from this website: Oxford British Journal of Anaesthesia
1) There are opoids regularly used that do not have central nervous system (CNS) effects.
"Thus, P-glycoprotein may limit morphine entry into the brain. Loperamide, a widely used anti-diarrhoeal agent, although a potent opioid in vitro, produces only gastrointestinal opioid effects and lacks CNS effects. This apparent tissue selectivity is probably a result of loperamide being a P-glycoprotein substrate, so that P-glycoprotein in the CNS effectively prevents access of loperamide to the CNS. Supportive of this hypothesis is the finding that in mice with MDR1 gene disruption, brain loperamide concentrations were 8-fold higher than those observed in normal mice, and lethal opioid effects were produced."
2) There is widespread variation between individuals, although there tends to be ethnic differences seen in genetic response to drugs. While I haven't yet found info about arab's responses to codeine, 6-7% of white people don't metabolize it either.
"The effects and side-effects of any drug will significantly depend on the genetic impact on its pharmacokinetics and pharmacodynamics. An active drug which is metabolized slowly by a person with increased receptor sensitivity may cause toxic effects, while an active drug which is metabolized extensively by a person with reduced receptor sensitivity, may have a reduced effect."
"As new drugs are introduced into clinical practice, it will be important to assess whether they are P-glycoprotein substrates or inhibitors to assess their potential for drug interaction. Inter-individual variability in P-glycoprotein activity is now recognized, which may at least partially depend on genetic polymorphism. Homozygosity for an allele associated with deficient P-glycoprotein activity occurs in 24% of white people"
Codeine is ineffective as an analgesic in 6–7% of a Caucasian population as a result of homozygosity for non-functional CYP2D6 mutant alleles. CYP2D6 deficient patients will not convert codeine to morphine. Postoperative pain treatment with codeine-containing drugs will therefore have limited effect in patients with this trait, whose request for larger doses of codeine could easily be misinterpreted as drug addiction. This genetic variation makes it not surprising that a standardized prescription of codeine for pain relief will result in remarkable variation in the adequacy of pain relief.
I'm going to keep looking, but ask the pharmacists on the board to speak up if they know anything about this. (Kim?)