The impact of genetic factors on response to anaesthetics

Mikstacki, Adam; Skrzypczak-Zielińska, Marzena; Tamowicz, Barbara; Zakerska-Banaszak, Oliwia; Szalata, Marlena; Słomski, Ryszard

doi:10.2478/v10039-012-0065-z

Cited by 29 publications

(18 citation statements)

References 40 publications

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“…10,25,26 Because propofol is metabolized by CYP2C9 and UGT1A9, 27 it was expected that valproic acid would be an independent predictor of delayed emergence. On the other hand, clobazam is a weak inducer of CYP3A4 and has the potential to induce UGT1A1, but it does not have a significant induction or inhibition effect on CYPs at clinically meaningful concentrations in vitro.…”

Section: Discussionmentioning

confidence: 99%

Independent Predictors of Delay in Emergence From General Anesthesia

Miyagawa¹,

Higuchi²,

Ishii-Maruhama³

et al. 2015

Anesthesia Progress

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Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.

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Section: Discussionmentioning

confidence: 99%

Independent Predictors of Delay in Emergence From General Anesthesia

Miyagawa¹,

Higuchi²,

Ishii-Maruhama³

et al. 2015

Anesthesia Progress

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“…Changes between individuals in the pharmacokinetics of propofol result in differences in the required dose of anaesthetic needed for efficient general anaesthesia (Karwacki et al 2014). 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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“…There are several factors that may cause variations in postoperative recovery, i.e. co-morbidity 1 age, gender 2,3 , type and length of surgery and anaesthesia 1,4 , pain 5 , nausea 6 , genetics 7,8 .…”

Section: Introductionmentioning

confidence: 99%