Savvy Psychopharmacology

Making sense of CYP2D6 and CYP1A2 genotype vs phenotype

Current Psychiatry. 2018 July;17(7):41-45

References

1. Pharmacogene Variation Consoritum. CYP2D6 allele nomenclature. https://www.pharmvar.org/gene/CYP2D6. Updated May 22, 2018. Accessed June 11, 2018.
2. Mrazek D. Psychiatric pharmacogenomics. New York, NY: Oxford University Press; 2010:33,42,44,45,85.
3. Spina E, de Leon J. Clinical applications of CYP genotyping in psychiatry. J Neural Transm (Vienna). 2015;122(1):5-28.
4. Adedoyin A, Frye RF, Mauro K, et al. Chloroquine modulation of specific metabolizing enzymes activities: investigation with selective five drug cocktail. Br J Clin Pharmacol. 1998;46(3):215-219.
5. Filppula AM, Laitila J, Neuvonen PJ, et al. Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012;165(8):2787-2798.
6. U.S. National Library of Medicine. DailyMed. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed April 26, 2018.
7. Monte AA, Heard KJ, Campbell J, et al. The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness. Acad Emerg Med. 2014;21(8):879-885.
8. Preskorn SH, Kane CP, Lobello K, et al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine. J Clin Psychiatry. 2013;74(6):614-621.
9. de Leon, J, Susce, MT, Johnson, M, et al. DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping. CNS Spectr. 2009;14(1):19-34.
10. Lampe JW, King IB, Li S, et al. Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets. Carcinogenesis. 2000;21(6):1157-1162.
11. Zevin S, Benowitz NL. Drug interaction with tobacco smoking. An update. Clin Pharmacokinet. 1999;36(3):425-438.

CYP1A2 induction

A variety of medications and environmental factors may induce CYP1A2.

Medications. Certain medications may induce CYP1A2, including carbamazepine, phenytoin, rifampin, and primidone.

Cigarette smoking. A significant increase in smoking after 1 to 3 weeks may decrease drug levels, whereas a significant decrease in smoking after 1 to 3 weeks may result in elevated drug levels.³ Nicotine is not the causative agent of induction, but rather hydrocarbons found in cigarette smoke.¹¹

Diet. An increase in daily dietary intake of certain vegetables for 6 days has been shown to result in induction.³ Brassica (Cruciferae) vegetables such as broccoli (2 cups), cauliflower (1 cup), cabbage (1 cup), and radish sprouts (1/2 cup) have been found to increase CYP1A2 activity by 18% to 37%.¹⁰ Grilled meat also plays a role in induction.¹⁰

Related Resource

Ellingrod VL, Ward KM. Using pharmacogenetics guidelines when prescribing: What's available. Current Psychiatry. 2018;17(1):43-46.

Drug Brand Names

Amiodarone • Cordarone, Pacerone
Amitriptyline • Elavil, Endep
Aripiprazole • Abilify
Asenapine • Saphris
Atazanavir • Reyataz
Brexpiprazole • Rexulti
Bupropion • Wellbutrin, Zyban
Carbamazepine • Carbatrol, Tegretol
Chlorpromazine • Thorazine
Chloroquine • Aralen
Cinacalcet • Sensipar
Ciprofloxacin • Cipro
Citalopram • Celexa
Clozapine • Clozaril
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Diphenhydramine • Benadryl
Doxepin • Silenor
Duloxetine • Cymbalta
Escitalopram • Lexapro
Ethinyl estradiol • Estinyl
Fluoxetine • Prozac
Fluvoxamine • Luvox
Haloperidol • Haldol
Iloperidone • Fanapt
Imatinib • Gleevec
Imipramine • Tofranil
Mirtazapine • Remeron
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Paliperidone • Invega
Paroxetine • Paxil
Perphenazine • Trilafon
Phenytoin • Dilantin
Pimavanserin • Nuplazid
Primidone • Mysoline
Quetiapine • Seroquel
Quinidine • Cardioquin
Rifampin • Rifadin
Risperidone • Risperdal
Sertraline • Zoloft
Terbinafine • Lamisil
Thioridazine • Mellaril
Trazodone • Desyrel, Oleptro
Venlafaxine • Effexor
Vilazodone • Viibryd
Vortioxetine • Trintellix
Ziprasidone • Geodon

Making sense of CYP2D6 and CYP1A2 genotype vs phenotype

References

CYP1A2 induction

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