What medications inhibit 2D6?

Amitriptyline, clozapine, desipramine, flecainide, haloperidol, nortriptyline, risperidone, and valbenazine are examples of drugs that are eliminated by CYP2D6 metabolism. The presence of CYP2D6 inhibitors can increase levels of these drugs.

What is CYP2D6 inhibition?

CYP2D6 Inhibitors Drugs that inhibit CYP2D6 activity are likely to increase the plasma concentrations of certain medications, and, in some cases, adverse outcomes will occur (see Table 3 below right for a list of known inhibitors).

Are all SSRIs CYP2D6 inhibitors?

Most SSRIs are deactivated by CYP2D6; thus, CYP2D6 PMs are at elevated risk for SSRI overdose, which can result in drowsiness, tremor, nausea, vomiting, seizures, and coma. Therefore, administration of SSRIs in PMs and IMs should be approached with caution.

What is the importance of CYP2D6?

CYP2D6 is responsible for the metabolism of the second highest number of drugs metabolized by P450 enzymes. Substrates for CYP2D6 can be found in Table 3.1. CYP2D6 is a particularly challenging enzyme to understand and study because of its genetic polymorphism.

What foods inhibit CYP2D6?

Considerable evidence from both in vitro and animal studies suggests that CYP2D6 activity can be inhibited by goldenseal [59, 60], milk thistle [61, 62], kava kava [59, 63-65], Echinacea [59], and St. John’s wort [59, 66-68].

Does sertraline inhibit CYP2D6?

Sertraline, a selective serotonin reuptake inhibitor used to treat depression, inhibits CYP2D6 in vitro (Ki = 1.2 microM) less potently than fluoxetine (Ki = 0.15 microM).

Does atomoxetine inhibit CYP2D6?

Background: Atomoxetine, a selective norepinephrine reuptake inhibitor effective in the treatment of attention-deficit/hyperactivity disorder (ADHD), is metabolized through the cytochrome P-450 2D6 (CYP2D6) enzyme pathway, which is genetically polymorphic in humans.

Does alcohol inhibit CYP2D6?

Neither smoking nor alcohol affects CYP2D6 metabolizer status [96] . The CYP2D cluster of genes is contained on the long arm of chromosome 22 [8]. The enzymes in the cytochrome p450 monooxygenase system (CYP) are the major enzymes responsible for metabolizing medications.

Does paroxetine inhibit CYP2D6?

Paroxetine, a selective serotonin reuptake inhibitor, is a potent inhibitor of cytochrome P450 2D6 (CYP2D6) activity, but the mechanism of inhibition is not established.

What antidepressants are metabolized by CYP2D6?

CYP2D6 is involved in the metabolism of most antidepressants, and is primarily responsible for breakdown of amitriptyline, venlafaxine, fluoxetine and paroxetine among others. This enzyme also contributes to the metabolism of other antidepressants such as citalopram, duloxetine and mirtazapine.

Which of the following beta blockers is not metabolized by CYP2D6?

Carvedilol: advantage: elimination does not depend on the kidney function; disadvantage: is metabolised (to a lesser extent than metoprolol) by CYP2D6. Other indications: atenolol or bisoprolol. Neither is metabolised by CYP2D6.

Are there any drugs that are dependent on CYP2D6?

It has been reported that a drug dose, response, and toxicity risk of beta-blockers and antidepressants is highly dependent on CYP2D6 pharmacogenetics ( Hicks et al., 2013 ). Moreover, the bioactivation of codeine to morphine requires CYP2D6 leading to reports of genetic influence of drug safety ( Koren et al., 2006 ).

What makes CYP2D6 different from other CYP450 enzymes?

An attribute specific to CYP2D6 in comparison to other CYP450 enzymes is the presence of gene duplications that may confer an ultrarapid metabolizer phenotype. These polymorphisms are designated CYP2D6* (gene variant)XN, where XN refers to the number of gene copies. For example, CYP2D6*1X2 represents two copies of CYP2D6*1.

Which is the defective allele of the CYP2D6 gene?

The CYP2D6 ∗ 4 allele was the first defective CYP2D6 variant allele to be identified (in 1990) and constitutes the main explanation for the poor metabolizer (PM) phenotype among Caucasians [49]. CYP2D6 variants have been shown to affect mRNA transcripts and alter proteins and catalytic activity, all affecting drug metabolism [50].

How many CYP2D6 genotypes are there in the world?

A number of polymorphisms have been identified and the frequency of these alleles differ with the specific population examined.37 The majority of poor metabolizers have the CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6 genotypes, whereas ultrarapid metabolizers have multiple copies of CYP2D6*1, CYP2D6*2, or CYP2D6*35 genotypes. 38