Conceptually driven pharmacologic approaches to acute trauma.
Conceptually driven pharmacologic approaches to acute trauma.
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概念驱动的急性创伤药理学方法。
DOI：
10.1017/s109285290001943x
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发表时间：
2005
期刊：
影响因子：
3.3
通讯作者：
Delahanty,DouglasL
中科院分区：
文献类型：
--
作者：
Pitman,RogerK;Delahanty,DouglasL
创伤后应激障碍（PTSD）的二级预防需要在创伤事件发生后进行干预，以防止PTSD的发展。这方面的精神药理学研究很少。这是令人惊讶的，因为创伤后应激障碍是最明确的原因和发病的精神障碍。在本文提出的PTSD发病机制的转化模型中：创伤性事件（无条件刺激）过度刺激内源性应激激素（无条件反应）;这些介导事件记忆痕迹的过度巩固;响应于提醒（条件刺激）回忆事件;释放进一步的应激激素（条件反应）;这些导致进一步的过度巩固;并且过度巩固的记忆产生PTSD症状。基底外侧杏仁核中的去甲肾上腺素能亢进被假设为介导该周期。用α2-肾上腺素能激动剂或阿片类药物阻止突触前去甲肾上腺素释放，或用β-肾上腺素能拮抗剂（如普萘洛尔）阻断突触后去甲肾上腺素受体，可减少神经增强的记忆和恐惧条件反射。两个对照研究的创伤受害者提出的急诊室表明，创伤后普萘洛尔减少随后的创伤后应激障碍，作为一个自然主义的临床研究吗啡治疗烧伤儿童。皮质醇既增强记忆巩固，又减少记忆提取，导致混合预测。两项针对重症监护病房患者的对照研究发现，皮质醇可以减轻创伤后应激障碍。一项研究并未发现苯二氮卓类药物能有效预防创伤后应激障碍。选择性5-羟色胺再摄取抑制剂、抗癫痫药和α2-肾上腺素能激动剂尚未尝试。
Secondary prevention of posttraumatic stress disorder (PTSD) entails intervening in the aftermath of a traumatic event to forestall the development of PTSD. There has been little psychopharmacologic research in this area. This is surprising, given that PTSD is the mental disorder with the most clearly identified cause and onset. In a translational model of PTSD's pathogenesis presented herein: A traumatic event (unconditioned stimulus) overstimulates endogenous stress hormones (unconditioned response); these mediate an overconsolidation of the event's memory trace; recall of the event in response to reminders (conditioned stimulus); releases further stress hormones (conditioned response); these cause further overconsolidation; and the overconsolidated memory generates PTSD symptoms. Noradrenergic hyperactivity in the basolateral amygdala is hypothesized to mediate this cycle. Preventing pre-synaptic norepinephrine release with α2-adrenergic agonists or opioids, or blocking post-synaptic norepinephrine sreceptors with β-adrenergic antagonists such as propranolol, reduces hormonally enhanced memories and fear conditioning. Two controlled studies of trauma victims presenting to emergency rooms suggest that posttrauma propranolol reduces subsequent PTSD, as does one naturalistic clinical study of morphine treatment of burned children. Cortisol both enhances memory consolidation and reduces memory retrieval, leading to mixed predictions. Two controlled studies of intensive care unit patients found that cortisol reduced PTSD. One study did not find benzodiazepines effective in preventing PTSD. Selective serotonin reuptake inhibitors, antiepileptics, and α2-adrenergic agonists have yet to be tried.