Pharmacogenetics-guided analgesics in major abdominal surgery: Further benefits within an enhanced recovery protocol

Senagore, Anthony J.; Champagne, Bradley J.; Dosokey, Eslam; Brady, Justin T.; Steele, Scott R.; Reynolds, Harry L.; Stein, Sharon L.; Delaney, Conor P.

doi:10.1016/j.amjsurg.2016.11.008

Cited by 38 publications

(37 citation statements)

References 40 publications

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“…Side effects introduced by use of these agents may be detrimental to enhanced recovery practice and must be carefully monitored and managed as appropriate. However, as new agents emerge into clinical practice there are exciting prospects of more specifically tailoring analgesia for the individual patient, informed in the future by predictive pharmaco‐genetic information . Given the ageing population and associated co‐morbidities of patients presenting for surgery, other pain related issues such as post‐operative cognitive dysfunction and chronic pain must be considered, and accommodated, in pain management plans within the enhanced recovery program.…”

Section: Discussionmentioning

confidence: 99%

Enhanced recovery after surgery: Pain management

Nimmo

Foo

Paterson

2017

Journal of Surgical Oncology

129

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Effective pain management is fundamental to enhanced recovery after surgery. Selection of strategies should be tailored to patient and operation. As well as improving the quality of recovery, effective analgesia reduces the host stress response, facilitates mobilization and allows resumption of oral intake. Multi-modal regimens combining paracetamol, non-steroidal anti-inflammatory agents where indicated, a potent opioid and a local anaesthetic technique achieve effective analgesia while limiting the dose and thereby side effects of any one agent.

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Section: Discussionmentioning

confidence: 99%

Enhanced recovery after surgery: Pain management

Nimmo

Foo

Paterson

2017

Journal of Surgical Oncology

129

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“…The OPRM1 gene encodes for the μ‐opioid receptor, thus having a direct implication on the analgesic effect that fentanyl produces. Specifically, the A118G substitution is considered to underlie discrepancies in the analgesic requirements and sensitivity to opioids as it has been related with a reduced signal transduction, reduced expression of OPRM1 and reduced binding affinity for opioids such as morphine . This explains the higher dose requirements in people carrying the G allele.…”

Section: Discussionmentioning

confidence: 99%

“…It has shown reduced signal transduction and OPRM1 expression . Therefore, patients with the A/A genotype required lower morphine doses for effective analgesia …”

Section: Introductionmentioning

confidence: 99%

Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects

Saiz‐Rodríguez

Ochoa

Herrador

et al. 2018

Basic Clin Pharma Tox

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Fentanyl is an agonist of the μ‐opioid receptor commonly used in the treatment of moderate‐severe pain. In order to study whether pharmacogenetics explains some of the variability in the response to fentanyl, several genes related to fentanyl receptors, transporters and metabolic enzymes have been analysed. Thirty‐five healthy volunteers (19 men and 16 women) receiving a single 300 μg oral dose of fentanyl were genotyped for 9 polymorphisms in cytochrome P450 (CYP) enzymes (CYP3A4 and CYP3A5), ATP‐binding cassette subfamily B member 1 (ABCB1), opioid receptor mu 1 (OPRM1), catechol‐O‐methyltransferase (COMT) and adrenoceptor beta 2 (ADRB2) by real‐time PCR. Fentanyl concentrations were measured by ultra‐performance liquid chromatography combined with tandem mass spectrometry (UPLC‐MS/MS). Fentanyl pharmacokinetics is affected by sex. Carriers of the CYP3A4*22 allele, which is known to reduce the mRNA expression, showed higher area under the concentration‐time curve (AUC) and lower clearance (Cl) values. Although this finding might be of importance, its validity needs to be confirmed in other similar settings. Furthermore, carriers of the ABCB1 C1236T T/T genotype presented a lower AUC and higher Cl, as well as lower half‐life (T1/2). As volunteers were blocked with naltrexone, the effect of fentanyl on pharmacodynamics might be biased; however, we could observe that fentanyl had a hypotensive effect. Moreover, ADRB2 C523A A allele carriers showed a tendency towards reducing systolic blood pressure. Likewise, OPRM1 and COMT minor allele variants were risk factors for the development of somnolence. CYP3A5*3, ABCB1 C3435T and ABCB1 G2677T/A were not associated with fentanyl's pharmacokinetics, pharmacodynamics and safety profile.

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“…The vast majority of articles are related to pharmacokinetics, metabolism and adverse reactions of NSAIDs, such as gastrointestinal bleeding,2–6,10,12,13,28 but not the clinical control of inflammatory signs after surgical procedures. Some articles have shown pharmacogenetic impacts on large surgeries, such as the need for prior genetic analysis of patients before bariatric surgeries, regarding the lower use of opioids and lower rates of postoperative pain;29 The study of Murto et al30 shows the impact of CYP2C9*3 on lower postoperative pain rates after adenotonsillectomy surgeries in children taking celecoxib.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with <em>CYP2C8*3</em> and <em>CYP2C9</em>

Calvo

Zupelari-Gonçalves

Dionísio

et al. 2017

JPR

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ObjectiveNonsteroidal anti-inflammatory drugs (NSAIDs) are metabolized by the cytochrome P450 enzymes (CYPs), predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days) after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer’s overall satisfaction.Materials and methodsFor this purpose, 102 volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic DNA was isolated from saliva collected from volunteers subjected to invasive lower third molar surgeries, and the preoperative, intraoperative and postoperative parameters were collected and analyzed.ResultsAn equal amount of piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with visual analog pain scores typically <40 mm for all genotypes investigated. Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and CYP2C9*3 reported adverse side effects.ConclusionIn general, slow metabolizers of piroxicam, who were volunteers with mutant alleles, were indifferent from normal metabolizers with the wild-type alleles and therefore did not require specialized piroxicam doses to manage postoperative pain and inflammation.

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Pharmacogenetics-guided analgesics in major abdominal surgery: Further benefits within an enhanced recovery protocol

Cited by 38 publications

References 40 publications

Enhanced recovery after surgery: Pain management

Enhanced recovery after surgery: Pain management

Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects

Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with <em>CYP2C8*3</em> and <em>CYP2C9</em>

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