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DiMaria S, Mangano N, Bruzzese A, Bartula B, Parikh S, Costa A. Genetic Variation and Sex-Based Differences: Current Considerations for Anesthetic Management. Curr Issues Mol Biol 2025; 47:202. [PMID: 40136457 PMCID: PMC11941548 DOI: 10.3390/cimb47030202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 02/27/2025] [Accepted: 03/05/2025] [Indexed: 03/27/2025] Open
Abstract
Biomedical sciences have made immense progress and numerous discoveries aimed at improving the quality of life and life expectancy in modern times. Anesthesiology is typically tailored to individual patients as its clinical effects depend on multiple factors, including a patient's physiological and pathological states, age, environmental exposures, and genetic variations. Sex differences are also paramount for a complete understanding of the effects of specific anesthetic medications on men and women. However, women-specific research and the inclusion of women in clinical trials, specifically during child-bearing years, remain disproportionately low compared to the general population at large. This review describes and summarizes genetic variations, including sex differences, that affect responses to common anesthetic medications such as volatile anesthetics, induction agents, neuromuscular blocking drugs, opioids, and local anesthetics. It also discusses the influence of genetic variations on anesthesia outcomes, such as postoperative nausea and vomiting, allergic reactions, pain, depth of anesthesia, awareness under anesthesia and recall, and postoperative delirium.
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Affiliation(s)
- Stephen DiMaria
- Department of Anesthesiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA; (S.D.); (N.M.); (S.P.)
| | - Nicholas Mangano
- Department of Anesthesiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA; (S.D.); (N.M.); (S.P.)
| | - Adam Bruzzese
- Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.B.); (B.B.)
| | - Benjamin Bartula
- Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (A.B.); (B.B.)
| | - Shruti Parikh
- Department of Anesthesiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA; (S.D.); (N.M.); (S.P.)
| | - Ana Costa
- Department of Anesthesiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, USA; (S.D.); (N.M.); (S.P.)
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Zeng S, Qing Q, Xu W, Yu S, Zheng M, Tan H, Peng J, Huang J. Personalized anesthesia and precision medicine: a comprehensive review of genetic factors, artificial intelligence, and patient-specific factors. Front Med (Lausanne) 2024; 11:1365524. [PMID: 38784235 PMCID: PMC11111965 DOI: 10.3389/fmed.2024.1365524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Precision medicine, characterized by the personalized integration of a patient's genetic blueprint and clinical history, represents a dynamic paradigm in healthcare evolution. The emerging field of personalized anesthesia is at the intersection of genetics and anesthesiology, where anesthetic care will be tailored to an individual's genetic make-up, comorbidities and patient-specific factors. Genomics and biomarkers can provide more accurate anesthetic protocols, while artificial intelligence can simplify anesthetic procedures and reduce anesthetic risks, and real-time monitoring tools can improve perioperative safety and efficacy. The aim of this paper is to present and summarize the applications of these related fields in anesthesiology by reviewing them, exploring the potential of advanced technologies in the implementation and development of personalized anesthesia, realizing the future integration of new technologies into clinical practice, and promoting multidisciplinary collaboration between anesthesiology and disciplines such as genomics and artificial intelligence.
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Affiliation(s)
- Shiyue Zeng
- Zhuzhou Clinical College, Jishou University, Jishou, China
| | - Qi Qing
- Zhuzhou Clinical College, Jishou University, Jishou, China
| | - Wei Xu
- Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, China
| | - Simeng Yu
- Zhuzhou Clinical College, Jishou University, Jishou, China
| | - Mingzhi Zheng
- Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, China
| | - Hongpei Tan
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, China
| | - Junmin Peng
- Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, China
| | - Jing Huang
- Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, China
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Peter JU, Dieudonné P, Zolk O. Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example. Pharmaceuticals (Basel) 2024; 17:473. [PMID: 38675433 PMCID: PMC11054797 DOI: 10.3390/ph17040473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 03/27/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
Midazolam, a short-acting benzodiazepine, is widely used to alleviate patient anxiety, enhance compliance, and aid in anesthesia. While its side effects are typically dose-dependent and manageable with vigilant perioperative monitoring, serious cardiorespiratory complications, including fatalities and permanent neurological impairment, have been documented. Prolonged exposure to benzodiazepines, such as midazolam, has been associated with neurological changes in infants. Despite attempts to employ therapeutic drug monitoring for optimal sedation dosing, its efficacy has been limited. Consequently, efforts are underway to identify alternative predictive markers to guide individualized dosing and mitigate adverse effects. Understanding these factors is crucial for determining midazolam's suitability for future administration, particularly after a severe adverse reaction. This article aims to elucidate the factors influencing midazolam's pharmacokinetics and pharmacodynamics, potentially leading to adverse events. Finally, a case study is presented to exemplify the complex investigation into the causative factors of midazolam-related adverse events.
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Affiliation(s)
- Jens-Uwe Peter
- Institute of Clinical Pharmacology, Immanuel Klinik Rüdersdorf, Brandenburg Medical School, 15562 Rüdersdorf, Germany;
| | - Peter Dieudonné
- Department of Anesthesiology, University Hospital Ulm, 89081 Ulm, Germany
| | - Oliver Zolk
- Institute of Clinical Pharmacology, Immanuel Klinik Rüdersdorf, Brandenburg Medical School, 15562 Rüdersdorf, Germany;
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Ding Y, Liu A, Wang Y, Zhao S, Huang S, Zhu H, Ma L, Han L, Shu S, Zheng L, Chen X. Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine. Front Genet 2023; 14:1187415. [PMID: 37693312 PMCID: PMC10483403 DOI: 10.3389/fgene.2023.1187415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 08/09/2023] [Indexed: 09/12/2023] Open
Abstract
Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences. Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype. Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation. Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.
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Affiliation(s)
- Yuanyuan Ding
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Aiqing Liu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yafeng Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuai Zhao
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiqian Huang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyu Zhu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lulin Ma
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linlin Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaofang Shu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lidong Zheng
- Department of Anesthesiology, Lu’an Hospital Affiliated to Anhui Medical University, Lu’an, China
| | - Xiangdong Chen
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Affiliation(s)
- Stephanie Pan
- From the Department of Anesthesiology, Perioperative and Pain Medicine Stanford University School of Medicine, Stanford, California
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Mi SC, Wu LY, Xu ZJ, Zheng LY, Luo JW. Effect of modified ShengYangYiwei decoction on painless gastroscopy and gastrointestinal and immune function in gastric cancer patients. World J Gastrointest Endosc 2023; 15:376-385. [PMID: 37274559 PMCID: PMC10236977 DOI: 10.4253/wjge.v15.i5.376] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/28/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Painless gastroenteroscopy is a widely developed diagnostic and treatment technology in clinical practice. It is of great significance in the clinical diagnosis, treatment, follow-up review and other aspects of gastric cancer patients. The application of anesthesia techniques during manipulation can be effective in reducing patient fear and discomfort. In clinical work, the adverse drug reactions of anesthesia regimens and the risk of serious adverse drug reactions are increased with the increase in propofol application dose application dose; the application of opioid drugs often causes gastrointestinal reactions, such as nausea, vomiting and delayed gastrointestinal function recovery, after examination. These adverse effects can seriously affect the quality of life of patients.
AIM To observe the effect of modified ShengYangYiwei decoction on gastrointestinal function, related complications and immune function in patients with gastric cancer during and after painless gastroscopy.
METHODS A total of 106 patients with gastric cancer, who were selected from January 2022 to September 2022 in Xiamen Traditional Chinese Medicine Hospital for painless gastroscopy, were randomly divided into a treatment group (n = 56) and a control group (n = 50). Before the examination, all patients fasted for 8 h, provided their health education, and confirmed if there were contraindications to anesthesia and gastroscopy. During the examination, the patients were placed in the left decubitus position, the patients were given oxygen through a nasal catheter (6 L/min), the welling needle was opened for the venous channel, and a multifunction detector was connected for monitoring electrocardiogram, oxygen saturation, blood pressure, etc. Naporphl and propofol propofol protocols were used for routine anesthesia. Before anesthesia administration, the patients underwent several deep breathing exercises, received intravenous nalbuphine [0.nalbuphine (0.025 mg/kg)], followed by intravenous propofol [1.propofol (1.5 mg/kg)] until the palpebral reflex disappeared, and after no response, gastroscopy was performed. If palpebral reflex disappeared, and after no response, gastroscopy was performed. If any patient developed movement, frowning, or hemodynamic changes during the operation (heart rate changes during the operation (heart rate increased to > 20 beats/min, systolic blood pressure increased to > 20% of the base value), additional propofol [0.propofol (0.5 mg/kg)] was added until the patient was sedated again. The patients in the treatment group began to take the preventive intervention of Modified ShengYangYiwei decoction one week before the examination, while the patients in the control group received routine gastrointestinal endoscopy. The patients in the two groups were examined by conventional painless gastroscopy, and the characteristics of the painless gastroscopies of the patients in the two groups were recorded and compared. These characteristics included the total dosage of propofol during the examination, the incidence of complications during the operation, the time of patients' awakening, the time of independent activities, and the gastrointestinal function of the patients after examination, such as the incidence of reactions such as malignant vomiting, abdominal distension and abdominal pain, as well as the differences in the levels of various immunological indicators and inflammatory factors before anesthesia induction (T0), after conscious extubation (T1) and 24 h after surgery (T2).
RESULTS There was no difference in the patients’ general information, American Society of Anesthesiologist classification or operation time between the two groups before treatment. In terms of painless gastroscopy, the total dosage of propofol in the treatment group was lower than that in the control group (P < 0.05), and the time of awakening and autonomous activity was significantly faster than that in the control group (P < 0.05). During the examination, the incidence of hypoxemia, hypotension and hiccups in the treatment group was significantly lower than that in the control group (P < 0.01). In terms of gastrointestinal function, the incidences of nausea, vomiting, abdominal distension and abdominal pain in the treatment group after examination were significantly lower than those in the control group (P < 0.01). In terms of immune function, in both groups, the number of CD4+ and CD8+ cells decreased significantly (P < 0.05), and the number of natural killer cells increased significantly (P < 0.05) at T1 and T2, compared with T0. The number of CD4+ and CD8+ cells in the treatment group at the T1 and T2 time points was higher than that in the control group (P < 0.05), while the number of natural killer cells was lower than that in the control group (P < 0.05). In terms of inflammatory factors, compared with T0, the levels of interleukin (IL) -6 and tumor necrosis factor-alpha in patients in the two groups at T1 and T2 increased significantly and then decreased (P < 0.05). The level of IL-6 at T1 and T2 in the treatment group was lower than that in the control group (P < 0.05).
CONCLUSION The preoperative use of modified ShengYangYiwei decoction can optimize the anesthesia program during painless gastroscopy, improve the gastrointestinal function of patients after the operation, reduce the occurrence of examination-related complications.
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Affiliation(s)
- Sui-Cai Mi
- Department of Oncology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361000, Fujian Province, China
| | - Ling-Yan Wu
- Department of Nephropathy, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361000, Fujian Province, China
| | - Zheng-Jin Xu
- Department of Nephropathy, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361000, Fujian Province, China
| | - Li-Yan Zheng
- Department of Anesthesiology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361000, Fujian Province, China
| | - Jian-Wen Luo
- Department of Oncology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361000, Fujian Province, China
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Zhao S, Huang S, Zhong Q, Han L, Wang Y, Xu F, Ma L, Ding Y, Xia L, Chen X. Study of the Association of Single Nucleotide Polymorphisms in Candidate Genes With Sevoflurane. J Clin Pharmacol 2023; 63:91-104. [PMID: 35943164 DOI: 10.1002/jcph.2138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/03/2022] [Indexed: 01/07/2023]
Abstract
The susceptibility of different individuals to anesthetics varies widely, and sevoflurane is no exception. We hypothesized that polymorphisms in genes involved in pharmacokinetics and pharmacodynamics may explain this variation. A total of 151 individuals undergoing otorhinolaryngology surgery were included. The influence of genetic polymorphisms on sevoflurane sensitivity were investigated through SNaPshot technology. Individuals carrying KCNK2 rs6686529 G > C, MTRR rs3733784 TT, rs2307116 GG, or rs1801394 AA polymorphisms had a higher sensitivity to the sedative effect of sevoflurane than those without those polymorphisms. The univariate linear regression analysis indicated that MTRR rs3733784 TT, rs2307116 GG, and rs1801394 AA were potentially significant predictors of higher sensitivity to the sedative effect of sevoflurane. Moreover, CYP2E1 rs3813867 G > C and rs2031920 C > T, GABRG1 rs279858 T > C, KCNK3 rs1275988 CC, GRIN2B rs1806201 GG, MTRR rs2307116 G > A, and rs1801394 A > G were associated with a higher sensitivity to the cardiovascular effect of sevoflurane. Our results suggested that 9 single nucleotide polymorphisms in genes involved in metabolizing enzymes, transport proteins, target proteins of sevoflurane and folate metabolism may help to explain individual differences in the susceptibility to the sedative or cardiovascular effect of sevoflurane.
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Affiliation(s)
- Shuai Zhao
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shiqian Huang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Zhong
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Linlin Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yafeng Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Xu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lulin Ma
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuanyuan Ding
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Leiming Xia
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiangdong Chen
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Zeng Y, Cao S, Chen M, Fang C, Ouyang W. GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility. Pharmgenomics Pers Med 2022; 15:105-117. [PMID: 35173461 PMCID: PMC8841664 DOI: 10.2147/pgpm.s348170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 01/24/2022] [Indexed: 12/22/2022] Open
Affiliation(s)
- Youjie Zeng
- Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China
| | - Si Cao
- Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China
| | - Minghua Chen
- Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China
| | - Chao Fang
- Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China
- Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of China
| | - Wen Ouyang
- Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China
- Correspondence: Wen Ouyang, Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China, Email
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Montejano J, Jevtovic-Todorovic V. Anesthesia and Cancer, Friend or Foe? A Narrative Review. Front Oncol 2022; 11:803266. [PMID: 35004329 PMCID: PMC8735748 DOI: 10.3389/fonc.2021.803266] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/08/2021] [Indexed: 12/26/2022] Open
Abstract
Cancer remains the leading cause of death worldwide with close to 10 million deaths reported annually. Due to growth of the advanced age cohort in our population, it is predicted that the number of new cancer cases diagnosed between now until 2035 is to reach potentially 24 million individuals, a staggering increase in a relatively short time period. For many solid tumors, surgical resection along with chemotherapy is the best available approach to a potential cure which leads to almost 80% of cancer patients undergoing at least one surgical procedure during the course of their disease. During surgical intervention, the exposure to general anesthesia can be lengthy, complex and often involves various modalities resulting in an important question as to the role, if any, anesthesia may play in primary recurrence or metastatic conversion. Many components of the stress and inflammatory responses exhibited in the perioperative period can contribute to cancer growth and invasion. The agents used to induce and maintain general anesthesia have variable interactions with the immune and neuroendocrine systems and can influence the stress response during surgery. Thus, debating the best type of anesthesia that would help to attenuate sympathetic and/or pro-inflammatory responses while modulating cytokine release and transcription factors/oncogenes remains at the forefront. This may affect inducible cancer cell survival and migratory abilities not only intra-operatively, but also during the immediate post-operative phase of recovery. The ultimate question becomes how and whether the choice of anesthesia may influence the outcomes of cancer surgery with two major approaches being considered, i.e., regional and general anesthesia as well as the various hypnotics, analgesics and sympatholytics commonly used. In this review, we will address the latest information as to the role that anesthesia may play during cancer surgery with specific focus on primary recurrence and metastasis.
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Affiliation(s)
- Julio Montejano
- School of Medicine, University of Colorado, Aurora, CO, United States
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Bach-Rojecky L, Čutura T, Lozić M, Kliškinjić IH, Matišić V, Primorac D. Personalized Anesthetic Pharmacology. PERSONALIZED MEDICINE IN ANESTHESIA, PAIN AND PERIOPERATIVE MEDICINE 2021:65-92. [DOI: 10.1007/978-3-030-53525-4_3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care. J Pers Med 2020; 10:jpm10030065. [PMID: 32708157 PMCID: PMC7564657 DOI: 10.3390/jpm10030065] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 07/05/2020] [Accepted: 07/17/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Precision medicine represents an evolving approach to improve treatment efficacy by modifying it to individual patient's gene variation. Pharmacogenetics, an applicable branch of precision medicine, identifies patient's predisposing genotypes that alter the clinical outcome of the drug, hence preventing serious adverse drug reactions. Pharmacogenetics has been extensively applied to various fields of medicine, but in the field of anesthesiology and preoperative medicine, it has been unexploited. Although the US Food and Drug Administration (FDA) has a table of pharmacogenomics biomarkers and pharmacogenetics, this table only includes general side effects of the included drugs. Thus, the existing FDA table offers limited information on genetic variations that may increase drug side effects. Aims: The purpose of this paper is to provide a web-based pharmacogenomics search tool composed of a comprehensive list of medications that have pharmacogenetic relevance to perioperative medicine that might also have application in other fields of medicine. Method: For this investigation, the FDA table of pharmacogenomics biomarkers in drug labeling was utilized as an in-depth of drugs to construct our pharmacogenetics drug table. We performed a literature search for drug-gene interactions using the unique list of drugs in the FDA table. Publications containing the drug-gene interactions were identified and reviewed. Additional drugs and extracted gene-interactions in the identified publications were added to the constructed drug table. Result: Our tool provides a comprehensive pharmacogenetic drug table including 258 drugs with a total of 461 drug-gene interactions and their corresponding gene variations that might cause modifications in drug efficacy, pharmacokinetics, pharmacodynamics and adverse reactions. This tool is freely accessible online and can be applied as a web-based search instrument for drug-gene interactions in different fields of medicine, including perioperative medicine. Conclusion: In this research, we collected drug-gene interactions in a web-based searchable tool that could be used by physicians to expand their field knowledge in pharmacogenetics and facilitate their clinical decision making. This precision medicine tool could further serve in establishing a comprehensive perioperative pharmacogenomics database that also includes different fields of medicine that could influence the outcome of perioperative medicine.
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Bach-Rojecky L, Vađunec D, Lozić M, Žunić K, Špoljar GG, Čutura T, Erceg D, Primorac D. Challenges in anesthesia personalization: resolving the pharmacogenomic puzzle. Per Med 2019; 16:511-525. [DOI: 10.2217/pme-2019-0056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Clinicians are witnessing differences in the doses required for induction and maintenance of anesthesia, as well as prolonged recovery in some patients. Predictable factors like patient characteristics, factors related to the procedure, pharmacological characteristics of anesthetics and adjunctive drugs, might explain some of the observed differences. However, the role of various polymorphisms of genes encoding for drugs’ molecular targets, transporters and metabolic enzymes can have a significant impact on anesthesia outcome, too. In the present paper, we critically discuss pharmacological characteristics of the most common drugs used in anesthesia, with a focus on the possible genetic background of unpredictable diversities in anesthesia outcomes.
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Affiliation(s)
- Lidija Bach-Rojecky
- Department of Pharmacology, University of Zagreb Faculty of Pharmacy & Biochemistry, Zagreb 10000, Croatia
| | - Dalia Vađunec
- Department of Pharmacology, University of Zagreb Faculty of Pharmacy & Biochemistry, Zagreb 10000, Croatia
| | - Marin Lozić
- Department of Anesthesia & ICU Care of Neurosurgical Patients, Clinic for Anesthesia & Intensive Care, University Clinical Hospital Zagreb, Zagreb 10000, Croatia
| | | | | | - Tomislav Čutura
- St. Catherine Specialty Hospital, Zagreb 10000 & Zabok 49210, Croatia
| | - Damir Erceg
- St. Catherine Specialty Hospital, Zagreb 10000 & Zabok 49210, Croatia
- Croatian Catholic University, Zagreb 10000, Croatia
- Srebrnjak Children's Hospital, Zagreb 10000, Croatia
- University Josip Juraj Strossmayer Faculty of Dental Medicine & Health, School of Medicine, Osijek 31000, Croatia
- University Josip Juraj Strossmayer School of Medicine, Osijek 31000, Croatia
| | - Dragan Primorac
- St. Catherine Specialty Hospital, Zagreb 10000 & Zabok 49210, Croatia
- University Josip Juraj Strossmayer Faculty of Dental Medicine & Health, School of Medicine, Osijek 31000, Croatia
- University Josip Juraj Strossmayer School of Medicine, Osijek 31000, Croatia
- Eberly College of Science, State College, Penn State University, PA 16802, USA
- The Henry C. Lee College of Criminal Justice & Forensic Sciences, University of New Haven, West Haven, CT 06516, USA
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What we can learn from Big Data about factors influencing perioperative outcome. Curr Opin Anaesthesiol 2019; 31:723-731. [PMID: 30169341 DOI: 10.1097/aco.0000000000000659] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
PURPOSE OF REVIEW This narrative review will discuss what value Big Data has to offer anesthesiology and aims to highlight recently published articles of large databases exploring factors influencing perioperative outcome. Additionally, the future perspectives of Big Data and its major pitfalls will be discussed. RECENT FINDINGS The potential of Big Data has given an incentive to create nationwide and anesthesia-initiated registries like the MPOG and NACOR. These large databases have contributed in elucidating some of the rare perioperative complications, such as declined cognition after exposure to general anesthesia and epidural hematomas in parturients. Additionally, they are useful in finding patterns such as similar outcome in subtypes of beta-blockers and lower incidence of pneumonia in preoperative influenza vaccinations in the elderly. SUMMARY Big Data is becoming increasingly popular with the collaborative collection of registries offering anesthesia a way to explore rare perioperative complications and outcome to encourage further hypotheses testing. Although Big Data has its flaws in security, lack of expertise and methodological concerns, the future potential of analytics combined with genomics, machine learning and real-time decision support looks promising.
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Perioperative Assessment and Intraoperative Core Concepts in the Complex Kidney Patient. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0204-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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