GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.
GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.
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DOI：
10.2174/1570159x13666141210215423
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Jones AW
中科院分区：
文献类型：
--
作者：
Busardò FP;Jones AW
滥用的非法娱乐性药物γ-羟基丁酸酯（GHB）是一种强效中枢神经系统兴奋剂，在对活人和死人进行法医调查时经常遇到。伽马--羟丁酸钠盐注册为治疗剂（Xyrem®），在一些国家被批准用于治疗发作性睡病相关的昏厥，（Alcover®）是酗酒者解毒和戒断的辅助药物。在包括大脑在内的各种组织中，可内源性产生微量的伽马--羟丁酸（0.5-1.0毫克/升），伽马--羟丁酸在大脑中既是主要抑制性神经递质γ-氨基丁酸的前体，也是其代谢物。现有资料表明，伽马-羟丁酸在γ-氨基丁酸能系统中起神经递质或神经调质的作用，特别是通过与γ-氨基丁酸-B受体亚型结合。虽然伽马--羟丁酸在许多国家被列为受管制物质，但由于前体药物γ-丁内酯和1，4-丁二醇的供应，滥用现象仍在继续，这些药物不受管制。摄入后，GBL和BD均迅速转化为GHB（t1/2 ~1分钟）。20-40分钟后达到最大值，然后GHB从血浆中消除，半衰期为30-50分钟。只有约1-5%的GHB剂量可从尿液中回收，检测窗口相对较短（3-10小时）。这就要求在法医个案工作中需要药物使用和/或滥用证据时迅速取样。伽马-羟丁酸的娱乐剂量不容易估计，血浆中浓度约为100毫克/升时会产生欣快感和解除抑制，而500毫克/升则可能因心肺抑制而导致死亡。目前还没有有效的解毒剂来逆转伽马-羟丁酸的镇静和中毒作用。中毒患者需要支持性护理，应监测生命体征，并保持呼吸道通畅，以防呕吐。长期经常使用伽马--羟丁酸后，产生耐受性和依赖性，突然停止使用药物会导致令人不快的戒断症状。除了服用苯二氮卓类药物外，没有循证方案处理伽马--羟丁酸戒断问题。
The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from administering benzodiazepines.