Pharmacogenetics and anaesthesia: the value of genetic profiling

Landau, Ruth; Bollag, Laurent; Kraft, John C.

doi:10.1111/j.1365-2044.2011.06918.x

Cited by 124 publications

(14 citation statements)

References 161 publications

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“…Propofol was not used in this patient group, because it can only be administered (at least at our institution) with full anesthesiology coverage, which was not available, but midazolam and meperidine were utilized in all patients. Presumably, the fact that some patients had recall of their colonoscopy indicates a variation in response to the drugs based on difference in the interactions of clinical evaluation, pharmacogemonic [11; 33], or sex differences. As noted above, individuals may therefore require different doses of drugs to achieve a level of effective sedation.…”

Section: Discussionmentioning

confidence: 99%

Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy

Becerra

Aasted

Boas

et al. 2016

Pain

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Colonoscopy is an invaluable tool for screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of the current study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8±9.1; 6 female) undergoing routine colonoscopy (i.e., no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. NIRS data captured during the procedure was analyzed offline to evaluate the brains’ responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients’ facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. While some patients report recollection of procedural pain following the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia.

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Section: Discussionmentioning

confidence: 99%

Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy

Becerra

Aasted

Boas

et al. 2016

Pain

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“…This variability is mostly assigned to the genetic polymorphism of genes coding for enzymes participating in the biotransformation pathway of propofol (Kübler 2005; Mikstacki et al 2013). The need for gene profiling in anaesthesia has been suggested many times recently (Landau et al 2012). …”

Section: Introductionmentioning

confidence: 99%

The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia

Mikstacki¹,

Zakerska-Banaszak

Skrzypczak-Zielińska

et al. 2016

J Appl Genetics

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Propofol (2,6-diisopropylphenol) is one of the safest and most commonly used anaesthetic agents for intravenous general anaesthesia. However, in clinical practice, a large inter-individual variability in response to propofol is observed. To limit the risk of adverse effects, pharmacogenetic investigations are recommended. The aim of our study was to verify the impact of genetic changes c.516G>T in the CYP2B6, c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes on the individual propofol pharmacokinetic profile in the Polish patients undergoing general anaesthesia. Eighty-five patients from the Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poland, anaesthetised with propofol for surgery, were enrolled in the study. We have genotyped CYP2B6, UGT1A9 and CYP2C9 polymorphisms with the use of pyrosequencing. HPLC measurements of propofol plasma concentration were applied for a pharmacokinetic analysis of the anaesthetic. We identified poor (20), intermediate (42) and rapid (23) metabolisers of propofol, which constituted 24%, 49% and 27% of the group, respectively. Homozygotes c.516 T/T in the CYP2B6 gene were statistically more often found in the rapid metabolisers group (p < 0.05). However, polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol. The mean propofol retention time (MRT) correlated with the patient’s body mass index (BMI) (p < 0.05). From all the analysed changes, only polymorphism c.516G>T in the CYP2B6 gene and BMI affect the metabolism rate of propofol and may play an important role in the optimisation of propofol anaesthesia.

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“…However, after the death of breastfed neonate through morphine overdose by his mother taking codeine, the safety profile of codeine was reevaluated and FDA published a warning on codeine use in nursing mothers [152]. It is suggested that codeine should be avoided in breastfeeding mothers, who are extensive metabolizers (EMs) or UMs of CYP2D6 [153, 154]. The European Medicines Agency started a review of codeine-containing medicines on October 3, 2012, as well [155].…”

Section: Drug Metabolismmentioning

confidence: 99%

Pharmacogenetics of Chronic Pain and Its Treatment

Světlík

Hronová

Bakhouche

et al. 2013

Mediators of Inflammation

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This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of analgesics and other drugs used for chronic pain treatment. Several candidate genes have been identified in the literature, while there is usually only limited clinical evidence substantiating for the penetration of the testing for these candidate biomarkers into the clinical practice. Further, the pain-perception regulation and modulation are still not fully understood, and thus more complex knowledge of genetic and epigenetic background for analgesia will be needed prior to the clinical use of the candidate genetic biomarkers.

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Pharmacogenetics and anaesthesia: the value of genetic profiling

Cited by 124 publications

References 161 publications

Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy

Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy

The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia

Pharmacogenetics of Chronic Pain and Its Treatment

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