CYP2D6
- metabolizes about 20% of all drugs: codeine - 2D6 metabolizes to morphine, antidepressants like most SSRIs, TCAs, buproprion, tamoxifen, antipsychotics - haldol, risperidone, chlorpromazine, beta blocker, opiates
- can ask "Does codeine/tylenol 3 work for you" - if no, then they are likely CYP 2D6 mutants.
- problematic because there are lots of polymorphisms, duplicate copies, pseudogenes
- CYP2D6 can be mutated to the point where people are "ultrarapid metabolizers" - common in middle east
- "Generally, for European Caucasians and their descendants, the functional group of alleles are predominant, with a frequency of 71%. Non-functional alleles represent 26% of the variability, mainly CYP2D6*4. In Asians and their close descendants, functional alleles represent only ~ 50% of the frequency of CYP2D6 alleles. Asians and Pacific Islanders have a high frequency (median = 41%) of a reduced function allele, CYP2D6*10, contributing to the population shift to the right of metabolic rates indicating slower metabolism. Information concerning Amerindians from North (Canada), Central and South America indicate comparatively low frequencies of CYP2D6*10, perhaps a ”founders“effect. The frequency of functional alleles in Africans and African Americans is also about 50%. Both Africans and African Americans have reduced function alleles representing 35% of allele variation, mainly CYP2D6*17. African Americans, however, have more than twice the median frequency of nonfunctional alleles compared with Africans (14.5% vs. 6.3%)."{pharmacogenomics}

CYP3A4 
- metabolize about 25-50% of all drugs.
- notable drugs metabolized by CYP3A4 that lead to toxicities when combined with cyp inhibitors:
Steroids (budesonide, dexamethasone, fluticasone) - cushing's syndrome
PDE5 inhibitors (sildenafil, tadalfil) - hypotension, syncope
Vinblastine - bone marrow suppression
Vincristine - peripheral neuropathy, ileus
Pimozide - torsades
simvastatin - rhabdo
Benzos - excessive CNS depression
Carbamazepine - HA, vomiting, dizziness
Antiarrhythmics (disopyrimide, quinidine) - arrhythmias
Ergots - ergotism (peripheral ischemia, cyanosis, hypertension)