Pharmacogenetics: implications for obstetric anesthesia.

Service d'Anesthésiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
International Journal of Obstetric Anesthesia (Impact Factor: 1.83). 11/2005; 14(4):316-23. DOI: 10.1016/j.ijoa.2005.03.005
Source: PubMed
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    ABSTRACT: Abstract In recent years, exceptional progress has been observed in pharmacogenetics, i.e. investigations of inherited conditioning of the organism's response to drugs or xenobiotics. On the other hand, modern molecular biology techniques have been implemented, making it possible to perform studies determining the involvement of genetic factors in differing responses to agents employed in general anaesthesia. Unexpected and incorrect response of the organism to the administration of specific anaesthetics is most commonly associated with a genetic defect of the metabolic pathway of a given agent or its receptor. The majority of agents used in anaesthesia are metabolised in the liver by the cytochrome P450 superfamily enzymes (CYPs) and phase II drug-metabolising enzymes: glutathione S-transferases (GSTs), sulphotransferases (SULTs), UDPglucuronosyltransferases (UGTs) and NAD(P)H:quinone oxidoreductase (NQO1). Propofol is presently widely used for gastrointestinal (GI) and several other procedures. Among genes associated with metabolism of the most commonly applied anaesthetics such as propofol and sevoflurane, the following ones can be mentioned: CYP2E1, CYP2B6, CYP2C9, GSTP1, UGT1A9, SULT1A1 and NQO1. Moreover, the basic mechanism of propofol action involves its interaction with an ionotropic receptor GABAA inhibiting transfer of nerve impulses. Molecular studies have shown that polymorphic changes in GABRG2 receptor gene turn out to be important in the propofol anaesthesia. Planning of optimal anaesthesia can be considerably assisted by the determination of genetic factors of prognostic value taking advantage of genotyping and making it possible to select anaesthetics and reduce risk of side effects as well as undesirable actions.
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    ABSTRACT: Recent literature on the anaesthetist's role in the management of the patient with severe pre-eclampsia is reviewed, with particular emphasis on the role of regional anaesthesia. Laboratory findings in pre-eclamptic women include increased levels of markers of oxidative stress and circulating tyrosine kinase 1, and inflammatory activation of leucocytes. Magnesium sulphate is the most effective agent for seizure prophylaxis. The optimal pharmacological agents for acute control of blood pressure remain controversial. The benefits of epidural analgesia in labour are well established. Single-shot spinal anaesthesia for caesarean section is safe in the absence of contraindications. Successful use of combined spinal-epidural anaesthesia has been described. Most studies on maternal haemodynamics have employed heart rate and blood pressure data as surrogate measures of cardiac output. Noninvasive cardiac output studies provide further insight into the haemodynamic response during neuraxial techniques for caesarean section. The value of regional anaesthesia cannot be over-emphasized. Recent research into spinal anaesthesia for caesarean section suggests a lower susceptibility to hypotension and probably less impairment of cardiac output than in healthy parturients. Noninvasive cardiac output measurement may also have advantages in critical care management.
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