MedGen

Nortriptyline is a tricyclic that can be identified by the secondary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in cytochrome P450 2D6 (CYP2D6) may affect treatment success of nortriptyline or other tricyclics with the secondary amine functional group. Patients with poor metabolizer variants of CYP2D6 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for nortriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Codeine, an opioid analgesic, is used for the treatment of pain. It is metabolized by cytochrome P450-2D6 (CYP2D6) to morphine, an active metabolite with pain-relief action. The CYP2D6 gene has many polymorphisms that result in different enzyme activities. An individual can be an ultrarapid, normal, intermediate, or poor metabolizer of codeine, based on their CYP2D6 genotype. The CYP2D6 ultrarapid phenotype is associated with a higher risk of severe toxicity when treated with codeine, due to increased metabolism of codeine and thus enhanced morphine formation. Conversely, the CYP2D6 poor metabolizer phenotype is associated with ineffective pain relief from codeine treatment due to reduced formation of morphine. Accordingly, therapeutic recommendations for codeine based on an individual’s CYP2D6 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in Clinical Pharmacology and Therapeutics and are available on the PharmGKB website. [from PharmGKB]