| BackgroundPharmacodynamics tramaclol is a centrally acting synthetic non-opioid analgesic compound, structurally related to morphine or codeine.It, reprents a centrally acting opioid agonist with some selectivity for -receptor(1/6000 compared with morphine) and also binds weakly to K - and6- receptors (1/25 compared with - receptor). Tramadol also acts on the monoamine system by inhibiting primarily the reuptake of noradrenaline(NA) and serotonin(5-HT). Tramadol is a racemic mixture, consisting of 50% (+)- and 50% (-)-enantiomers. ( + ) -enantiomer primarily is responsible for acting on -receptor and inhibiting the reuptake of 5-HT, (-)-enantiomer primarily is responsible for inhibiting the reuptake of NA.Tramadol is biotransformed mainly through CYP2D6 to the metabolite, M1 and M2: (+)-0-demethyl-tramadol (-)-O-clemethy 1-tramadol. Only the one metabolite (mono-0-desmethyltramaclol denoted Ml) is pharmacologically active that is dependent on liver 0-demethylation byCYP2D6 isoenzyme of cytochrome P-450. Ml has higher affinity binding Lo -opioid receptors than tramadol. The amount of Ml depends on liver CYP2D6. Cytochrome P450 2D6 (CYP2D6) is the primary part of the multiplefunctional oxidative enzyme system depending on cytochrome P450. Cytochrome P450 lies in many body organs , such as liver , kidney, brain , etc, but the cytochrome P450 in liver cell has more significance in metabolizing drugs. Genetic polymorphisms wi thin the P4BO family are one of the most important causes resulting in the di (Terence of metabolizing ability among different races or individuals. CYP2D6 may metabolize about 30% of the whole drugs that are metabolized by cytochrome P450. Tramadol is a typical substrate of CYP2D6. There are few genetic polymorphisms within the CYP2D6 gene, the mutation frequence of genetic polymorphism diverse among Caucasians and Chinese, about 7%-10% of Caucasians and 1 % of Chinese are poor metaholizers (PMs) of CYP2D6 metabolized drugs. These individuals have reduced activity in this pathway resulting in higher AUCs, higher peak plasma concentrations, and slower elimination (higher plasma half-life) of many drugs compared with people with normal activity (EMs, extensive metabolizers). Jerling suggests that the clearence rate of BZ of KMs is 3 times longer than that of PMs. The polymorphism results in marked difference in the effection and action duration of drug clinically and sometimes cause cumulation and poisoning. The genetic polymorphisms of CYP2D6 may be associated with the decrease of tranadol metabolizating action, so do Ml and the analfesic action of tramadol. It was suggested that the plasma concentration of tramadol has great difference between individuals during postoperativeanalgesia .If we get the genotype before using tramado] as analgesia , we may use tramadol safely and decrease the incidence of side effect.ObjectiveTo investigate the individual response to tramadol , the plasma concentration of tramadol in posteroperative intravenous analgesia and correlation with the genotype of CYP2D6, to guide the individual prevention and treatment of acute and chronic pain. Methods86ASAI-II patients (Male:42, Female:44 ) undergoing abdominal surgery were enrolled. Premedication included midazolam 5mg and atropine 0.5 mg i.m .Anesthesia was induced with propofol 2mg/kg, fenfanyl 5-6 g/kg and vecuronium 0.08-0.12 mg/kg. matintained with isoflurane inhalation of 0.8%-2.0% isoflurane , intermittent iv boluses of vecuronium and fentanyl if necessary. At the end of operation a loading dose of tramadol 1.5mg/kg was givien intravenously over 1 min .followed by continuous intravenous infusion of tramadol for 48 hours. All patients received tramadol infusion at the rate of 18 mg/h .Venous blood samples were taken from all the patients at 8, 24, 44h during postoperative tramadol infusion for determination of plasma concentration of tramadol by high performance liquid chromatography(HPLC). The patients were also genotyped. Efficacy of analgesia was assessed by VAS score. The patients...
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