■急性间非他明毒性的特征是兴奋剂作用和神经精神障碍,这是由γ-氨基丁酸A型受体激动剂,包括苯二氮卓。我们利用临床注册数据来检查在非法药物病例中共同暴露于γ-氨基丁酸B型受体激动剂(γ-羟基丁酸酯)的影响,并经分析证实暴露于metamfetamine。
■澳大利亚维多利亚州的新兴药物网络是一个伦理委员会批准的前瞻性注册表,收集急诊科非法药物介绍的临床和分析数据(利用血液样本)。比较组通过分析证实的暴露来定义:单独的氨非他明,间苯丙胺加γ-羟基丁酸酯,间非他明加苯二氮卓,间非他明+γ-羟基丁酸酯+苯二氮卓。排除同时接触其他兴奋剂或镇静剂的病例。
■间非他明血药浓度中位数在间非他明+γ-羟基丁酸酯中显著更大(n=153,中位数=0.20mg/L,四分位数间距:0.10-0.32mg/L,95%置信区间:0.20-0.23mg/L)和间非他明+γ-羟基丁酸酯+苯二氮卓(n=160,中位数=0.20mg/L,四分位数间距:0.10-0.30mg/L,95%置信区间:0.20-0.30mg/L)阳性组与γ-羟基丁酸酯阴性组(n=81,中位数=0.10mg/L,四分位数间距:0.05-0.21mg/L,95%的置信区间:0.09-0.18mg/L)和metamfetamine+苯二氮卓(n=73,中位数=0.10mg/L,四分位数间距:0.06-0.20mg/L,95%置信区间:0.09-0.20mg/L)组(P<0.0004)。在异氨非他明加γ-羟丁酸的情况下呈现心率(n=153,中位数=72次/分钟,四分位间距:每分钟63-86次,95%的置信区间:每分钟70-78次跳动)显着低于metamfetamine加苯二氮卓类药物的情况(n=73,中位数=每分钟84次跳动,四分位间距:每分钟73-98次,95%的置信区间:每分钟80-90次,P<0.0001),和单独的氨非他明病例(n=81,中位数=每分钟110次,四分位间距:每分钟87-131次,95%置信区间:每分钟93-120次,P<0.0001)。甲氨氟胺加γ-羟基丁酸酯病例的温度(中位数=35.8°C,四分位数间距:35.0-36.2°C,95%置信区间35.6-35.9°C)显着低于metamfetamine加苯二氮卓类药物(中位数36.2°C,四分位数间距35.7-36.6°C,95%置信区间,36.0-36.4°C,P=0.017),和单独的间非他明病例(中位数=36.5°C,四分位数间距:35.8-37.1°C,95%置信区间:36.2-36.7°C,P<0.0001)。苯二氮卓阳性组的收缩压中位数显着降低(P≤0.001)(metamfetamine+苯二氮卓中位数=120mmHg,四分位数间距:109-132mmHg,95%置信区间:116-124mmHg和metamfetamine+苯二氮卓+γ-羟基丁酸中位数=124mmHg,四分位数间距:110-137mmHg,95%置信区间:120-129mmHg)。安非他明加γ-羟基丁酸酯的镇静发生率(格拉斯哥昏迷评分小于9分)(63%)明显高于安非他明加苯二氮卓类药物的发生率(27%,P<0.0001)和单独的氨非他明病例(15%,P<0.0001)。间非他明+γ-羟基丁酸酯+苯二氮卓类药物的躁动发生率显著较低(17%,P<0.0001)和氨非他明加γ-羟基丁酸酯病例(34%,P=0.0004)与单独的间非他明病例(58%)相比。
■γ-氨基丁酸A型和B型受体生理学的差异可能提供γ-氨基丁酸B型激动剂促进的替代药效学机制,能够减弱metamfetamine兴奋剂和神经精神毒性。
■分析证实与γ-羟基丁酸共同接触的Metamfetamine中毒患者的心率显着降低,与单独使用间非他明的患者相比,体温和躁动的发生率。与单独暴露于苯二氮杂卓的患者相比,分析证实的苯二氮杂卓共同暴露于苯二氮杂卓的中毒患者的收缩压显着降低。我们假设γ-氨基丁酸B型受体激动剂可能对急性间非他明毒性的治疗有益。
UNASSIGNED: Acute metamfetamine toxicity is characterized by stimulant effects and neuropsychiatric disturbance, which is attenuated by gamma-aminobutyric acid type A receptor agonists including benzodiazepines. We utilized clinical registry data to examine the effect of co-exposure to a gamma-aminobutyric acid type B receptor agonist (gamma-hydroxybutyrate) in illicit drug cases with analytically confirmed exposure to metamfetamine.
UNASSIGNED: The Emerging Drugs Network of Australia Victoria is an ethics board-approved prospective registry collecting clinical and analytical data (utilising blood samples) on emergency department illicit drug presentations. Comparison groups were defined by analytically confirmed exposure: lone metamfetamine, metamfetamine plus gamma-hydroxybutyrate, metamfetamine plus benzodiazepine, metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine. Cases with co-exposure to other stimulants or sedatives were excluded.
UNASSIGNED: Median metamfetamine blood concentrations were significantly greater in metamfetamine plus gamma-hydroxybutyrate (n = 153, median = 0.20 mg/L, interquartile range: 0.10-0.32 mg/L, 95 per cent confidence interval: 0.20-0.23 mg/L) and metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine (n = 160, median = 0.20 mg/L, interquartile range: 0.10-0.30 mg/L, 95 per cent confidence interval: 0.20-0.30 mg/L) positive groups compared to gamma-hydroxybutyrate negative groups including metamfetamine (n = 81, median = 0.10 mg/L, interquartile range: 0.05-0.21 mg/L, 95 per cent confidence interval: 0.09-0.18 mg/L) and metamfetamine plus benzodiazepine (n = 73, median = 0.10 mg/L, interquartile range: 0.06-0.20 mg/L, 95 per cent confidence interval: 0.09-0.20 mg/L) groups (P < 0.0004). Presenting heart rate in metamfetamine plus gamma-hydroxybutyrate cases (n = 153, median = 72 beats per minute, interquartile range: 63-86 beats per minute, 95 per cent confidence interval: 70-78 beats per minute) was significantly lower than metamfetamine plus benzodiazepine cases (n = 73, median = 84 beats per minute, interquartile range: 73-98 beats per minute, 95 per cent confidence interval: 80-90 beats per minute, P < 0.0001), and lone metamfetamine cases (n = 81, median = 110 beats per minute, interquartile range: 87-131 beats per minute, 95 per cent confidence interval: 93-120 beats per minute, P < 0.0001). Presenting temperature in metamfetamine plus gamma-hydroxybutyrate cases (median = 35.8 °C, interquartile range: 35.0-36.2 °C, 95 per cent confidence interval 35.6-35.9 °C) was significantly lower than metamfetamine plus benzodiazepine cases (median 36.2 °C, interquartile range 35.7-36.6 °C, 95 per cent confidence interval, 36.0-36.4 °C, P = 0.017), and lone metamfetamine cases (median = 36.5 °C, interquartile range: 35.8-37.1 °C, 95 per cent confidence interval: 36.2-36.7 °C, P < 0.0001). Median presenting systolic blood pressure was significantly (P ≤ 0.001) lower in benzodiazepine positive groups (metamfetamine plus benzodiazepine median = 120 mmHg, interquartile range: 109-132 mmHg, 95 per cent confidence interval: 116-124 mmHg and metamfetamine plus benzodiazepine plus gamma-hydroxybutyrate median = 124 mmHg, interquartile range: 110-137 mmHg, 95 per cent confidence interval: 120-129 mmHg). Incidence of sedation (Glasgow Coma Scale less than 9) was significantly greater in metamfetamine plus gamma-hydroxybutyrate cases (63 per cent) compared to metamfetamine plus benzodiazepine cases (27 per cent, P < 0.0001) and lone metamfetamine cases (15 per cent, P < 0.0001). Incidence of agitation was significantly lower in metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine cases (17 per cent, P < 0.0001) and metamfetamine plus gamma-hydroxybutyrate cases (34 per cent, P = 0.0004) compared to lone metamfetamine cases (58 per cent).
UNASSIGNED: Differences in gamma-aminobutyric acid type A and B receptor physiology may offer a gamma-aminobutyric acid type B agonist-facilitated alternative pharmacodynamic mechanism able to attenuate metamfetamine stimulant and neuropsychiatric toxicity.
UNASSIGNED: Metamfetamine intoxicated patients with analytically confirmed co-exposure to gamma-hydroxybutyrate had significantly reduced heart rate, body temperature and incidence of agitation compared to patients with lone metamfetamine exposure. Metamfetamine intoxicated patients with analytically confirmed co-exposure to a benzodiazepine had significantly reduced systolic blood pressure compared to patients with lone metamfetamine exposure. We hypothesize that gamma-aminobutyric acid type B receptor agonists may be beneficial in the management of acute metamfetamine toxicity.