CYP2D6
Cytochrome P450 2D6 is an enzyme that in humans is encoded by the CYP2D6 gene and a member of the cytochrome P450 mixed-function oxidase system.It's one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, in a process referred to as O-demethylation.
CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism.
There are 4 types:
poor metabolizer – little or no CYP2D6 function (those people won't feel much from codeine, as codeine is a prodrug and needs to be metabolized into morphine)
intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
extensive metabolizer – normal CYP2D6 function
ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function
Warnings:
poor metabolizer -> Don't take Dextromethorphan, as even normal therapeutical doses can make you trip for hours or even days, because you don't metabolize DXM well. This could potentially be lethal
ultrarapid metabolizer -> Don't take codeine, as you will metabolise codeine rapidly into morphine, thus increasing the risk of an overdose
Drugs that are metabilized by CYP2D6:
All tricyclic antidepressants, e.g.
imipramine, amitriptyline
Most SSRIs , e.g.
fluoxetine, paroxetine, fluvoxamine
venlafaxine
duloxetine
mianserin
mirtazapine
opioids
codeine
tramadol
O-desmethyltramadol
N-desmethyltramadol
oxycodone
hydrocodone
tapentadol
antipsychotics, e.g.
haloperidol
risperidone
perphenazine
thioridazine
zuclopenthixol
iloperidone
aripiprazole
chlorpromazine
levomepromazine
remoxipride
minaprine
tamoxifen
beta-blockers
metoprolol
timolol
alprenolol
carvedilol
bufuralol
nebivolol
propranolol
debrisoquine
Class I antiarrhythmics
flecainide
propafenone
encainide
mexiletine
lidocaine
sparteine
ondansetron
donepezil
phenformin
tropisetron
stimulants
amphetamine
methoxyamphetamine
dextromethamphetamine
atomoxetine
chlorphenamine
dexfenfluramine
dextromethorphan
metoclopramide
perhexiline
phenacetin
promethazine
Drugs that inhibit CYP2D6 (this will result in higher and longer blood concentration of the drugs mentioned above, this could lead to increased side effects and could even be lethal or to no effects at all):
White grapefruit juice
Strong
Certain SSRIs
fluoxetine
paroxetine
bupropion
quinidine
cinacalcet
ritonavir
Moderate
sertraline
duloxetine
terbinafine
Weak
amiodarone
buprenorphine
cimetidine
citalopram
escitalopram
Unspecified potency
antipsychotics
haloperidol
perphenazine
thioridazine
zuclopenthixol
risperidone
chlorpromazine
hyperforin (St. Johns Wort)
antihistamines
promethazine
chlorphenamine
diphenhydramine
hydroxyzine
tripelennamine
clemastine
celecoxib
clomipramine
cocaine
doxorubicin
metoclopramide
methadone
moclobemide
doxepin
halofantrine
levomepromazine
mibefradil
midodrine
ticlopidine
cannabidiol
Inducers of CYP2D6:
Strong
glutethimide
Unspecified potency
dexamethasone
rifampicin
From Wikipedia