Many medicines must be given at the same time to manage critically ill patients. Patients with comorbidities and drug-drug interactions may experience reduced drug efficacy or increased risk of adverse effects as a result. Children may be of specific concern since they could be more susceptible to negative drug reactions. Most current practices employ a one-size-fits-all approach to medication dosing. Alternatively, precision medicine examines an individual’s genetic profile and adjusts individual therapeutic doses based on the results. Testing for pharmacogenetic variations is not generally used, but it was employed to solve an established problem rather than being used proactively to enhance clinical care. To incorporate pharmacogenetics into medical practice, a deeper understanding of the frequency of clinically significant genetic variants in drug pathways is required and the identification of drugs most frequently impacted by a patient’s genetics. According to researchers, several patients may have one or more genetic variants in drug-metabolizing pathways used by one or more medications taken during hospitalization. Abnormal genetic variants in the primary drug pathways will be investigated, as well as what medications may be affected. To determine which drug-metabolizing pathways were involved in this adverse reaction, genetic data from 30 pediatric burn and surgery patients were collected. The investigators also studied drugs that were given to patients throughout their hospitalization and those potentially influenced by these variants. Analysis of 11 whole genome sequencing and 9 whole-exome sequencing data sets for haplotypes in cytochrome P450 (CYP) metabolizing enzymes was done with Aldy allelic decomposition software. The study also uncovered 15 additional patients with abnormal function in one or more of the following CYP genes: 2C9, 2C19, 2D6, 3A4 and 3A5. Most had reduced function, with the exception of several patients with CYP2C19 variants that had fast or ultrarapid phenotypes. Hydrocodone, oxycodone, methadone, ibuprofen, ketorolac, Celebrex, diazepam, famotidine, diphenhydramine and glycopyrrolate are just a few examples of drugs that use these pathways for primary metabolism when given during hospitalization. The study found that about 1/4 to 1/3 of people have functional genotypes in the primary drug metabolizing pathways. Study group need great future clinical research to validate the clinical significance of these haplotypes and the additional influence of drug-drug interactions and other clinical confounders on drug efficacy.
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