PharmGKB summary

Alvarellos, Maria L.; McDonagh, Ellen M.; Patel, Sephalie Y.; McLeod, Howard L.; Altman, Russ B.; Klein, Teri E.

doi:10.1097/fpc.0000000000000170

Cited by 26 publications

(12 citation statements)

References 66 publications

(94 reference statements)

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“…We found 20 anesthetic drugs composed of 7.75% of pharmacogenes. Inhaled anesthetic and intravenous opioid analgesic agents were the most common anesthetic medications that might induce a drug–gene interaction and potentially a subsequent intraoperative adverse event [ 12 , 17 , 18 ]. Genes that were mostly interacting with anesthetic drugs were CYP2D6 , RYR1 , CYP3A4 , BChE , and G6PD [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

Zarei

Costas

Orozco

et al. 2020

JPM

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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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Section: Resultsmentioning

confidence: 99%

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

Zarei

Costas

Orozco

et al. 2020

JPM

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“…Among the four missense variants (A, F 1 , F 2 , and K), the A and F variants are considered “qualitative” variants because they impair catalytic properties of the enzyme, while the K variant is “quantitative” because it affects the plasma BChE concentration and does not qualitatively change the encoded enzyme. 15 , 16 The K variant is in LD with variants in noncoding regions of the gene, which may cause reduced BChE expression. 14 , 17 , 18…”

Section: Resultsmentioning

confidence: 99%

Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine

Zhu

Dawson

Huskey

et al. 2020

PGPM

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Background: Genetic variants in the BCHE (butyrylcholinesterase) gene are associated with reduced BChE enzyme activity and prolonged post-succinylcholine neuromuscular blockade, which can lead to postanesthetic apnea and respiratory depression. Testing for BChE deficiency is usually performed by biochemical methods and is generally only offered to patients who have a personal or family history of prolonged post-succinylcholine neuromuscular blockade. Purpose: Using a clinical test, we investigated the frequencies of BCHE genotypes that are associated with increased risk for prolonged post-succinylcholine neuromuscular blockade. Materials and Methods: Five BCHE variants, including the A (atypical, rs1799807), K (Kalow, rs1803274), F 1 (fluoride-1, rs28933389), F 2 (fluoride-2, rs28933390), and S 1 (silent-1, rs398124632), were genotyped in a large (n = 13,301), multi-ethnic cohort in the United States. Subjects were recipients of pharmacogenetic testing ordered by their physicians as part of routine care. Results: The minor allele frequencies of A, K, F 1 , F 2 , and S 1 were 1.60%, 19.93%, 0.08%, 0.47%, and 0.04%, respectively, in this cohort. Based on a review of biochemical and clinical data of these variants, we grouped BCHE genotypes into four phenotypic categories to stratify the risk for prolonged post-succinylcholine neuromuscular blockade. Approximately 0.06% of patients were predicted to have severe BChE deficiency, 8% were predicted to have moderate BChE deficiency, and 29% were predicted to have mild BChE deficiency. Compared to other ethnic groups, Caucasians were predicted to have the highest frequency of BChE deficiency. Conclusion: While severe BChE deficiency is rare in the United States, approximately 8% of Americans are at moderate risk of prolonged post-succinylcholine neuromuscular blockade, suggesting that a sizable percentage of patients may benefit from preoperative genetic testing of BCHE.

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“…From a pharmacogenomics standpoint, genetic polymorphism of the butyrylcholinesterase (BCHE) enzyme is one of the most common examples of discrepancies in patients’ drug response in the perioperative settings.72 BCHE is responsible for metabolizing succinylcholine in the plasma and liver.73 Patients having mutant alleles (BCHE*FS126, BCHE*I3E4-14C, and BCHE*328D) have been shown to experience longer duration of muscle relaxation than patients with wild-type alleles.74 Specifically, patients with homozygous mutant alleles are susceptible to more prolonged relaxation than patients with heterozygous alleles.75 Thus, variability of genetic expression of this enzyme affects patients’ outcomes and could result in longer hospital stay with higher incidence of postoperative morbidity and mortality.76…”

Section: Neuromuscular Blockadementioning

confidence: 99%

Potential role of pharmacogenomics testing in the setting of enhanced recovery pathways after surgery

Awad¹,

Ahmed²,

Urman³

et al. 2019

PGPM

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In 2001, a group of European academic surgeons created the Enhanced Recovery After Surgery (ERAS) study group and established the first official ERAS protocol. One of the most significant challenges during ERAS implementation is variability of drugs used throughout the perioperative period. Pharmacogenomic testing (blood or saliva) results (obtained within approximately 48 hrs) provide guidelines on how to prescribe the optimal drug with the optimal dosage to each patient based on an individual’s unique genetic profile. Pharmacogenomic testing of various methods of multimodal analgesia is an essential element of ERAS protocols spanning the entire perioperative period to ultimately optimize postoperative pain control. The key goal for anesthetic management in ERAS protocols is to facilitate rapid emergence by using the shortest acting agents available, thus accelerating recovery and reducing length of stay, hospital expenses, and postoperative complications. Postoperative nausea and vomiting (PONV) is an additional challenge that should be overcome to ensure an enhanced recovery and shorter length of stay with the use of antiemetics. Postoperative ileus (POI) can result in longer hospital stay with increasing susceptibility to associated morbidities along with an increase in associated hospitalization costs. Genetics-guided pharmacotherapy and its impact on clinical outcomes should be thoroughly studied for better understanding and managing drug administration in the settings of ERAS.

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PharmGKB summary

Cited by 26 publications

References 66 publications

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

<p>Genetic Testing for <em>BCHE</em> Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine</p>

<p>Potential role of pharmacogenomics testing in the setting of enhanced recovery pathways after surgery</p>

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