Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

Zhou, Shuqin; Skaar, Debra J.; Jacobson, Pamala A.; Huang, R. Stephanie

doi:10.3389/fphar.2018.01436

Cited by 16 publications

(11 citation statements)

References 135 publications

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“…This finding raises a critical question of identification of the factors determining which patients are more likely to respond to treatment. Genetic factors have been shown to impact the efficacy of many therapies for various diseases [Berinstein and Levy, 2017, Matera et al, 2017, Politi et al, 2018, Yamamoto and Yano, 2018], and provide the basis for the development of “personalized medicine” [Di Paolo et al, 2017, Kent et al, 2018, Zhou et al, 2018]. Our results support the necessity of further research into the possibility of introducing personalized medicine into pain management.…”

Section: Discussionsupporting

confidence: 68%

Efficacy of acetaminophen versus ibuprofen for the management of rotator cuff-related shoulder pain: Randomized open-label study

AlRuthia

Alghadeer

Balkhi

et al. 2019

Saudi Pharmaceutical Journal

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BackgroundShoulder pain related to the rotator cuff (RC) is one of the most common and bothersome musculoskeletal complaints. Pharmacologic treatment most often includes acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However, data allowing comparison of the efficacy of these two drugs are very limited. We compared the therapeutic outcomes of acetaminophen and ibuprofen in the management of RC-related pain.MethodsThis was an open-label, two-center, active-control, prospective randomized clinical trial. Participants were assigned randomly to acetaminophen or ibuprofen treatment groups. The acetaminophen dose was 500 mg every 6–8 h, and it was 400–800 mg every 6–8 h for ibuprofen. The impact of the treatment was measured by Shoulder Pain and Disability Index (SPADI), Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) and World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires at baseline and after 6 weeks of therapy.ResultsThirty-three patients completed the study; 20 treated with ibuprofen and 13 with acetaminophen. Patients in both groups were comparable at baseline with regard to SPADI, Quick-DASH, and WHOQOL-BREF scores. After 6 weeks of treatment, patients receiving ibuprofen, but not acetaminophen, reported an improvement in pain severity and functional activity (as measured by SPADI and Quick-DASH). Patients taking acetaminophen, but not ibuprofen, reported improvement in the physical and environmental domains of WHOQOL-BREF scores.ConclusionsIbuprofen and acetaminophen provide benefits to patients suffering from RC-related pain. However, the type of improvement perceived by patients differed between these two medications.

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Section: Discussionsupporting

confidence: 68%

Efficacy of acetaminophen versus ibuprofen for the management of rotator cuff-related shoulder pain: Randomized open-label study

AlRuthia

Alghadeer

Balkhi

et al. 2019

Saudi Pharmaceutical Journal

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“…al heralded the potential for the utilization of pharmacogenetics in the ICU setting but noted numerous difficulties with its practical application. 22 Our current techniques provide a practical solution to many of these issues and allow us to receive pharmacogenetic data within 72 hours of ICU admission. Our enrollment of 20.5% of screened patients provides evidence for the feasibility of our approach and exceeds the enrollment rate of 5.7% from a recent large ICU delirium trial.…”

Section: Discussionmentioning

confidence: 99%

The Pharmacogenetics of Opiates and Its Impact on Delirium in Mechanically Ventilated Adults: A Pilot Study

Austin

Szeto

Gupta

et al. 2022

Journal of Pharmacy Technology

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Background: Pharmacogenetics may explain a substantial proportion of the variation seen in the efficacy and risk profile of analgesosedative drugs and the incidence of delirium in critically ill adults. Objectives: Conduct a feasibility study to demonstrate the reliability of collecting and analyzing pharmacogenetic information from critically ill patients and to assess the impact of pharmacogenetics on intensive care unit (ICU) outcomes. Methods: We prospectively enrolled subjects from the Medical ICU at the University of North Carolina (UNC). DNA was obtained via a buccal swab and evaluated using the DNA2Rx assay. We collected data on demographics, daily cumulative psychoactive medication exposure, and severity of illness. We performed daily delirium assessments via the CAM-ICU. We analyzed associations between select single nucleotide polymorphisms (SNPs) and delirium. Results: From June, 2018 through January, 2019, we screened 244 patients and enrolled 50. The median age was 62.0 years old (range: 28-82 years old), and 27 (54%) of the subjects were female. In all, 49 (98%) samples were both high quality and sufficient quantity. In secondary analyses, we found that 80% (12/15) of patients with two 2 copies of a G allele at rs4680 on COMT experienced delirium, whereas 44% (4/9) of patients with 2 copies of an A allele at this location had delirium. In all, 44% (4/9) of patients with 2 T allele copies at rs7439366 on UGT2B7 experienced delirium compared to 73% (11/15) of patients with 2 C allele copies at this location. Conclusions: We can feasibly collect genetic information from critically ill adults. We were able to efficiently collect high quality DNA of sufficient quantity to conduct pharmacogenetic analysis in this critically ill population. Although the sample size of our current study is too small to conduct robust inferential analyses, it suggests potential SNP targets for a future larger study.

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“…Pharmacogenetics (PGx) is a relatively young research field; it aims to translate laboratory genetic test information into clinical practice to help to understand inter-individual differences among patients and develop more accurate drug dosing [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Between July 2017 and 2019 we performed a prospective observational study to evaluate the effect of ACT on the sublingual microcirculation of pyrexial septic patients (NCT02750163, first registration 25/04/2016). We aimed to investigate, as secondary outcome of the study, what was the prevalence in our sample of CYP3A5 rs776746 and UGT1A1 rs8330 polymorphisms, and if a correlation existed between the presence of any of the two polymorphisms and ACT plasmatic concentration and body temperature reduction [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…CYP3A5 is the gene that encode for cytochromeP450 (CYP) 3A5 that is a protein responsible for converting ACT to N-acetylparaquinoneimine (NAPQI, an hepatotoxic metabolite) that is then detoxified by conjugation with glutathione. Rs776746 identify the genetic variant (A/G, at the genomic position 22,893 on chromosome 7) of CYP3A5 that is responsible for aberrant splicing of CYP3A5 mRNA, that results in a nonfunctional protein [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock

Scorcella¹,

Domizi²,

Amoroso

et al. 2023

BMC Anesthesiol

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Background Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. Methods Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. Results 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. Conclusions Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. Trial registration NCT02750163.

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Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

Cited by 16 publications

References 135 publications

Efficacy of acetaminophen versus ibuprofen for the management of rotator cuff-related shoulder pain: Randomized open-label study

Efficacy of acetaminophen versus ibuprofen for the management of rotator cuff-related shoulder pain: Randomized open-label study

The Pharmacogenetics of Opiates and Its Impact on Delirium in Mechanically Ventilated Adults: A Pilot Study

Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock

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