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Replies Reply Posts-Enzymes View your peers' presentation posts and respond to at least two classmates. In your reply post, answer the following questions: What did you find interesting about the presentation? What did you learn from this that you may not have during the reading? Are there any aspects of this topic that are still unclear? What do you plan to do to fill in these gaps in knowledge? Reply separately to two of your classmates’ post (see attached classmates, post#1 and post#2) Your response should include evidence-based research to support your statements using proper citations and APA format. Please, send me the two documents separately, for example one is the reply to my peers Post#1, and the second one is the reply to my other peer Post#2. -Minimum of 300 words per peer reply. -Turnitin Assignment. Background: I live in South Florida; I am currently enrolled in the Psych Mental Health Practitioner Program. I am a Family Nurse Practitioner working in psychiatric area. 1 CYP1A2 ENZYME 6 CYP 1A2 enzyme What is the CYP1A2 enzyme? The CYP1A2 enzyme is one of the major and essential enzymes of the CYP 450 (cytochrome P450) group or family (Guo et al., 2021). The CYP 450 family consists of various enzymes such as the CYP1A2 that are involved in the metabolism of various drugs (Guo et al., 2021). As such, the CYP1A2 is an essential detox enzyme that assists in breaking down the toxic chemicals, hormones, drugs, and other products leading to their elimination from the body (Saiz-Rodríguez et al., 2019). This enzyme occurs mainly in the liver, and it comprises about thirteen percent of the CYP enzymes (Guo et al., 2021). However, it is also found at lower levels in the lungs, intestines, brain, and pancreas (Guo et al., 2021). As such, this enzyme is inducible in various parts of the body that include; the liver, gastrointestinal tract, pancreas, brain, and lungs. Importance of the CYP1A2 The CYP1A2 is one of the major and essential drug-metabolizing enzymes in the liver that assists in breaking down the toxic chemicals, hormones, drugs, and other products in the body, which helps in their elimination from the body (Saiz-Rodríguez et al., 2019). For instance, it contributes to a significant percentage of the oxidative metabolism of several clinically relevant drugs (Saiz-Rodríguez et al., 2019). This enzyme is involved in the metabolism of various clinically relevant drugs that include Imipramine, Clozapine, Mexiletine, Cyclobenzaprine, and Theophylline. As such, the CYP1A2 usually helps in the breakdown and elimination of these drugs from the body. Additionally, it is recognized as the major metabolizing enzyme for caffeine (Koonrungsesomboon et al., 2018). This enzyme is also involved in the metabolism of various hormones like estrogens and Melatonin (Guo et al., 2021). It also helps in the breakdown of various toxic substances like aflatoxin B1 and polycyclic aromatic hydrocarbons. Overall, this enzyme is essential for the processing of various products and hormones and the elimination of toxic substances from the body. According to Koonrungsesomboon et al. (2018), the CYP1A2 enzyme is essential for dosing of various antipsychotics and evaluation of their efficacy as well as adverse drug reactions. What does it do in the human body? This enzyme plays a significant role in the metabolism of various medications like Ropinirole, Theophylline, Olanzapine, Haloperidol, and Clozapine (Guo et al., 2021). Additionally, it helps in the biotransformation of various endogenous compounds such as melatonin, aflatoxin B1, estrogens, heterocyclic/aromatic amines, bilirubin, and procarcinogens (Guo et al., 2021). As such, this enzyme helps in the breakdown of various toxic substances, hormones, drugs as well as other products, which helps in their elimination from the body (Guo et al., 2021). However, the CYP1A2 enzyme may activate some of the cancer-causing agents like aflatoxin B1 and heterocyclic/aromatic amines leading to the development of cancer. As such, decreased or increased activity of this enzyme is associated with an increased risk for cancer. What are the common medications that inhibit the enzyme, including any substrates? The medications that usually minimize or decrease the activity of this enzyme are referred to as the CYP1A2 inhibitors (Hakkola et al., 2020). Among the common medications that inhibit this enzyme include Atazanavir, Zileuton, Ciprofloxacin, Tacrine, Enoxacin, Cimetidine, and Artemisinin (Hakkola et al., 2020). For instance, Enoxacin, Ciprofloxacin, and Fluvoxamine are classified as some of the strong inhibitors of this enzyme (Hakkola et al., 2020). The moderate inhibitors of this enzyme include Mexiletine and Methoxsalen while the weak inhibitors include Cimetidine and Acyclovir (Hakkola et al., 2020). On the other hand, the medications that are usually metabolized by this enzyme are referred to as the CYP1A2 substrates (Hakkola et al., 2020). Some of the common CYP1A2 substrates include Olanzapine, Ropinirole, Clozapine, Alosetron, Flutamide, Theophylline, Mirtazapine, and Rasagiline (Hakkola et al., 2020). For instance, some of the sensitive substrates include Duloxetine, Alosetron, and Tizanidine while some of the medications or substrates that are moderately sensitive include Theophylline and Clozapine (Hakkola et al., 2020). What are the important medication restrictions regarding this enzyme? The CYP1A2 inhibitors usually minimize the metabolism as well as the efficacy or effectiveness of the substrate medications (Hakkola et al., 2020). The medications that inhibit this enzyme are associated with a high likelihood of increasing the concentrations of the substrate medications in the plasma that may lead to the occurrence of adverse outcomes (Hakkola et al., 2020). Thus, it is necessary to avoid the prescription and use of substrate medications alongside the associated inhibitors to prevent the occurrence of drug-drug interactions or adverse outcomes. For instance, it is necessary to avoid the prescription and use of clozapine or theophylline alongside the CYP1A2 inhibitors like fluvoxamine and ciprofloxacin. Additionally, the use of tizanidine and fluvoxamine usually leads to increased concentrations of Tizanidine in the plasma that results in the occurrence of adverse outcomes (Hakkola et al., 2020). Therefore, it is necessary to avoid the concurrent use of these medications to prevent the occurrence of adverse outcomes. Overall, the increased involvement of this enzyme in drug interactions underscores the need to promote appropriate use of the medications that are metabolized by this enzyme. Thus, it is necessary to avoid the concurrent use of substrates like Tizanidine, Theophylline, Olanzapine, and Clozapine together with potent inhibitors like Enoxacin, Ciprofloxacin, and Fluvoxamine to minimize the occurrence of adverse outcomes (Hakkola et al., 2020). References Guo, J., Zhu, X., Badawy, S., Ihsan, A., Liu, Z., Xie, C., & Wang, X. (2021). Metabolism and Mechanism of Human Cytochrome P450 Enzyme 1A2. Current Drug Metabolism, 22(1), 40-49. Hakkola, J., Hukkanen, J., Turpeinen, M., & Pelkonen, O. (2020). Inhibition and induction of CYP enzymes in humans: an update. Archives of toxicology, 1-52. Koonrungsesomboon, N., Khatsri, R., Wongchompoo, P., & Teekachunhatean, S. (2018). The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. The pharmacogenomics journal, 18(6), 760-768. Saiz-Rodríguez, M., Ochoa, D., Belmonte, C., Román, M., Vieira de Lara, D., Zubiaur, P., ... & Abad-Santos, F. (2019). Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. Journal of Psychopharmacology, 33(4), 522-531. CYP1A2 Enzyme by Edina Boros The following discussion will examine the enzyme CYP1A2, one of the five most significant enzymes in the cytochrome P450 (CYP) system (Stahl, 2013). This discussion post will detail the significance of this enzyme, the interaction with medications, and the impact on clinical practice. The Cytochrome P450 enzymes have an essential role in metabolizing drugs. Genetic variability can be a factor that influences the enzyme’s function. Each enzyme has a specific gene responsible for the function of that enzyme. The inherited alleles determine how a person responds to certain drugs. Specific medications can affect the operation of CYP 1A2 differently, leading to adverse reactions and therapeutic failure (Lynch&Neff, 2007). The enzyme CYP1A2 is expressed mainly in the liver but can be found in the small intestine, the lungs, the kidneys, and the placenta (Lynch &Neff, 2007). One or more CYP 450 enzymes can metabolize medications. CYP1A2 has a role in processing clozapine, olanzapine, fluvoxamine, haloperidol, theophylline, melatonin, bilirubin, estrogens, procarcinogens, and caffeine. Caffeine is almost entirely metabolized by CYP1A2. Caffeine consumption and cigarette smoking induce CYP1A2 activity, which should be considered when prescribing medications. Known methods of estimating enzyme activity are testing caffeine clearance or determining the concentration ratio of paraxanthine, the primary caffeine metabolite, to caffeine in a saliva sample (Urry et al., 2016). Some medications such as Amiodarone, cimetidine, ciprofloxacin, and fluvoxamine are potent inhibitors. Inhibition of the enzyme means that drug levels in the blood can reach higher than expected levels, which can be a potential safety issue (Alsanosi & Padmanabhan, 2014). Known inducers of CYP1A2 are Carbamazepine, phenobarbital, rifampin, tobacco. These substances can lower the desired serum level of certain medications. Although it happens with some delay, it has to be considered when added to medicines metabolized by the same enzyme. There are available substitute medications or increasing or decreasing the dosages of the target medication to avoid therapeutic failure or adverse effects. Substrates affecting the CYP1A2 enzymes are caffeine, clozapine, and theophylline (Lynch Neff, 2007). References Alsanosi, S. M. M., Padmanabhan, S. (2014). Enzyme inhibition. Enzyme Inhibition - an overview | ScienceDirect Topics. Retrieved September 17, 2021, from https://www.sciencedirect.com/topics/neuroscience/enzyme-inhibition. Ghodke-Puranik, Y. A., & Lamba, J. K. (2017). CYP1A2 - an overview | ScienceDirect Topics. Retrieved September 17, 2021, from https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp1a2. Lynch, T.,&Neff, A. P. (2007, August 1). The effect of Cytochrome P450 metabolism on Drug Response, interactions, and adverse effects. American Family Physician. Retrieved September 17, 2021, from https://www.aafp.org/afp/2007/0801/p391.html. Stahl, S. (2013). Essentials of Psychopharmacology, (4th edition). United Kingdom: Cambridge University Press. Urry, E., Jetter, A., & Landolt, H. P. (2016). Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual caffeine intake. Nutrition & metabolism, 13(1), 1-9. CYP1A2 Enzyme by Kourtnee Fitzgerald Cytochrome P450 is a family of enzymes that influence drug metabolism (Stahl, 2013; Woo & Robinson, 2020). Patients may have genetic mutations or polymorphisms of these enzymes which can impact their ability to metabolize certain drugs, and the extent of adverse reactions they may experience (McDonnell & Dang, 2013). CYP1A2 is part of this family of enzymes and comprises around 13% of CYP in the liver (Thorn et al., 2012). It contains several haplotypes including CYP1A2 *1A, 1F, 1C, and 1K (Thorn et al., 2012). This enzyme has a large role in activation of toxic xenobiotics, so has been studied not only for its role in drug metabolism, but also for its role in cancer risk and metabolism of carcinogens (Thorn et al., 2012). Smoking is an inducer of this enzyme, which can cause patients to require increased doses of medications that are substrates of CYP1A2 (Stahl, 2013). Medications that are substrates of this enzyme include olanzapine, duloxetine, and even ondansetron (McDonnell & Dang, 2013). CYP1A2 is essential to clozapine metabolism, and patients who are ultra-rapid metabolizers receive improved outcomes with increased dosing or co-administration of a CYP1A2 inhibitor such as fluvoxamine (Thorn et al., 2012). References: McDonnell, A. M., & Dang, C. H. (2013). Basic review of the cytochrome p450 system. Journal of the Advanced Practitioner in Oncology, 4(4), 263–268. https://doi.org/10.6004/jadpro.2013.4.4.7 Stahl, S. (2013). Essentials of psychopharmacology, (4th edition). United Kingdom, Cambridge University Thorn, C. F., Aklillu, E., Klein, T. E., & Altman, R. B. (2012). PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenetics and Genomics, 22(1), 73–77. https://doi.org/10.1097/FPC.0b013e32834c6efd Woo, T. M., & Robinson, M. V. (2020). Pharmacotherapeutics for advanced practice nurse prescribers (5th ed.). Philadelphia, PA: F.A. Davis Company.