Risk to heroin users of polydrug use of pregabalin or gabapentin
Risk to heroin users of polydrug use of pregabalin or gabapentin
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DOI：
10.1111/add.13843
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发表时间：
2017-09-01
期刊：
影响因子：
6
通讯作者：
Henderson, Graeme
中科院分区：
文献类型：
--
作者：
Lyndon, Abigail;Audrey, Suzanne;Henderson, Graeme
目的研究海洛因使用者同时使用加巴喷丁或普瑞巴林（加巴喷妥类药物）的风险。设计多学科研究：我们（a）检查了英格兰和威尔士药物相关死亡和加巴喷丁处方数据的趋势，以检验是否有证据表明，提及加巴喷丁或普瑞巴林的死亡增加与加巴喷丁处方的趋势有关，并与阿片类药物的使用有关;（B）采访了有海洛因使用史的人，了解他们使用加巴喷丁和普瑞巴林的多种药物;和（c）研究在小鼠中不存在和存在吗啡的情况下普瑞巴林的呼吸抑制作用，以确定伴随暴露是否增加观察到的呼吸抑制程度。设置英格兰和威尔士。对30名参与者（19名男性，11名女性）进行了访谈。测量：（a）国家统计局2004年1月1日至2015年12月31日期间涉及阿片类药物和普瑞巴林或加巴喷丁的药物相关死亡;（B）对普瑞巴林和加巴喷丁多药使用的可用性、使用、相互作用和影响的主观看法;（c）呼吸速率和深度。普瑞巴林和加巴喷丁处方每年增加约24%，从2004年的100万增加到2015年的1050万。涉及加巴喷妥的死亡人数从2009年之前的每年不到1人增加到2015年的137人;其中79%的死亡也涉及阿片类药物。死亡人数的增加与处方量的增加高度相关（相关系数0.94;每增加10万张处方，死亡人数增加5%）。海洛因使用者描述普瑞巴林很容易获得。他们认为，海洛因和普瑞巴林的组合加强了海洛因的作用，但担心它会引起“停电”，并增加过量的风险。在小鼠中，本身不抑制呼吸的低剂量S-普瑞巴林（20 mg/kg）逆转了对吗啡抑制呼吸的耐受性（导致35%的呼吸抑制，P < 0.05），而高剂量S-普瑞巴林（200 mg/kg）单独抑制呼吸，这种作用与吗啡的作用相叠加。结论：对于海洛因使用者，阿片类药物与加巴喷丁或普瑞巴林的组合可能会增加急性过量死亡的风险，通过逆转耐受性或药物抑制呼吸的累加效应。
Aim To examine the risk to heroin users of also using gabapentin or pregabalin (gabapentoids). Design Multidisciplinary study: we (a) examined trends in drug-related deaths and gabapentoid prescription data in England and Wales to test for evidence that any increase in deaths mentioning gabapentin or pregabalin is associated with trends in gabapentoid prescribing and is concomitant with opioid use; (b) interviewed people with a history of heroin use about their polydrug use involving gabapentin and pregabalin; and (c) studied the respiratory depressant effects of pregabalin in the absence and presence of morphine in mice to determine whether concomitant exposure increased the degree of respiratory depression observed. Setting England and Wales. Participants Interviews were conducted with 30 participants (19 males, 11 female). Measurements (a) Office of National Statistics drug-related deaths from 1 January 2004 to 31 December 2015 that mention both an opioid and pregabalin or gabapentin; (b) subjective views on the availability, use, interactions and effects of polydrug use involving pregabalin and gabapentin; and (c) rate and depth of respiration. Results Pregabalin and gabapentin prescriptions increased approximately 24% per year from 1 million in 2004 to 10.5 million in 2015. The number of deaths involving gabapentoids increased from fewer than one per year prior to 2009 to 137 in 2015; 79% of these deaths also involved opioids. The increase in deaths was correlated highly with the increase in prescribing (correlation coefficient 0.94; 5% increase in deaths per 100 000 increase in prescriptions). Heroin users described pregabalin as easy to obtain. They suggested that the combination of heroin and pregabalin reinforced the effects of heroin but were concerned it induced 'blackouts' and increased the risk of overdose. In mice, a low dose of S-pregabalin (20 mg/kg) that did not itself depress respiration reversed tolerance to morphine depression of respiration (resulting in 35% depression of respiration, P < 0.05), whereas a high dose of S-pregabalin (200 mg/kg) alone depressed respiration and this effect summated with that of morphine. Conclusions For heroin users, the combination of opioids with gabapentin or pregabalin potentially increases the risk of acute overdose death through either reversal of tolerance or an additive effect of the drugs to depress respiration.