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- QUESTION
Pharmacokinetic actions are mediated through the hepatic and gut drug-metabolizing system known as the cytochrome P540 (CYP) enzyme system. Select medications that you would likely prescribe or encounter frequently in your practice (ideally psychopharmaceutical agents).
Please answer the following questions, assigned by the first letter of your last name. Include at least two references other than Stahl in your answers. Also, please write two test questions covering the information in your initial post.
QUESTION: – Please state what the CYP 2D6 enzyme is, why it is important, and what it does in the body. List common medications, foods, herbs, and/or substances that inhibit this enzyme, including any substrates, and any important medication restrictions regarding this enzyme.
Don't forget to make up two simple test questions based from the question you wrote about. They do not need to be complicated with a simple answer is in maybe multiple choice form
| Subject | Nursing | Pages | 3 | Style | APA |
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Answer
Cytochrome P450 System
Pharmacokinetic actions are mediated through the hepatic and gut drug-metabolizing system known as the cytochrome P540 (CYP) enzyme system. This system produces enzymes that are involved in the synthesis as well as metabolism of different chemicals and molecules within the cells. The enzymes metabolize various external substances, for instance ingested medications, and those formed within the cells, for instance toxins. There are numerous Cytochromes P450 (CYP), each of which is influenced by a wide range of factors and mechanisms ranging from genetic polymorphism, hormonal regulation, cytokinetic regulation, age, and sex to xenobiotic induction just to mention but a few (Zanger & Schwab, 2013). This piece offers an overview of CYP 2D6.
CYP 2D6
CYP 2D6 is a noninducible protein-coding gene of the CYP2D subfamily. One of the most studied members of the CYP2 family and CYP2D subfamily, it is responsible for the metabolism of the second highest number of drugs that are metabolized by the P450 enzyme system (Herbet, 2013). According to Zanger and Schwab (2013),
“the number of drugs metabolized primarily by CYP2D6 is very large in comparison to its relatively minor expression in liver and includes ~15–25% of all clinically used drugs from virtually all therapeutic classes, like antiarrhythmics (e.g. propafenone, mexiletine, flecainide),tricyclic and second generation antidepressants (e.g. amitriptyline,paroxetine, venlafaxin), antipsychotics (aripiprazole, risperidone), βblockers (bufuralol, metroprolol), as well as anti-cancer drugs, in particular the selective estrogen receptor modifier (SERM) tamoxifen, several opioid analgesics including codeine and tramadol, and many others”(p.124).
While CYP2D6 represents only about 3% of hepatic CYP content, it accounts for the metabolism of about 20% of ingested drugs (Tirona et al.,2017). Some typical CYP2D6 substrates include beta-blockers, antiarrhythmics, opioid analgesics, and antidepressants. This enzyme stands out from others in the P450 system for the manner it remains uninduced by xenobiotic exposure. Significant clinical inhibition of this enzyme (hence decreased substrate drug metabolism) occurs in cases of cotreatment with cinacalcet and quinidine as well as serotonin reuptake inhibitors (like fluoxetine and paroxetine). Terbinafine and celecoxib also inhibit this enzyme. Notably, the compounds inhibiting this enzyme need not be substrates, so long as they can bind to it with high affinity, a good example being methadone. Another point worth noting is that while CYP2D6 is noninducible, it is said to be highly polymorphic with numerous gene duplications for nonfunctional and functional alleles. An ultrarapid metabolizer phenotype, which has been noted to be more prevalent among Africans than in Caucasians, is conferred by the said gene duplications.
This enzyme’s polymorphism is clinically significant, particularly in terms of ADRs and/or responses to the agents that the enzyme activates or inactivates. For example, CYP2D6 metabolically inactivates many antiarrhythmic drugs like timolo and metaprolol, leading to an increased risk of ADRs for IMs/PMs.
Test Questions
- List at least 10 therapeutic drugs that are metabolized by CYP2D6.
- State and explain at least two features of CYP2D6 that set it aside from other enzymes in its family/sub-family.
References
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Herbert, M.F. (2013). Clinical Pharmacology During Pregnancy. London: Academic Press. Tirona, R.G., & Kim, R.B. (2017). Clinical and Translational Science (Second Edition). London, Academic Press. Zanger,U.M., & Schwab, M.(2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138, 103-141.
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