Kovács G L
Institute of Diagnostics and Management, Faculty of Health Sciences, University of Pécs and Central Laboratory, Markusovszky Teaching Hospital, Szombathely, Hungary.
Curr Med Chem. 2003 Dec;10(23):2559-76. doi: 10.2174/0929867033456459.
Abrupt cessation of long-term alcohol consumption produces well-defined symptoms called alcohol withdrawal (AW). The exact pathophysiological mechanisms involved in the appearance of AW symptoms and particularly those related to the precipitation of delirium tremens (DT), still await clarification in spite of the fact that the prediction of complicated AW is essential to guarantee that appropriate therapies may be planned in advance. Changes in central nervous system (CNS) glutamate- and GABA-transmission and a role of voltage-operated calcium channels are equally important elements of neuroadaptation to the chronic presence of alcohol. In addition to the CNS regulation, however, changes in peripheral fluid and electrolyte homeostasis may accompany, and are expected to modify the clinical symptoms of AW. In an early phase of acute withdrawal, plasma levels of atrial natriuretic peptide (ANP), plasma renin activity and aldosterone are high. In patients with DT, elevated levels of ANP were observed days before the actual onset of DT. It is concluded that the altered plasma ANP secretion might be associated with, and therefore used as an indicator of the onset of DT. However, ANP is present in and produced by the brain and thus it can be regarded as a neuropeptide. The role of CNS ANP was studied in mice, rendered tolerant to and physically dependent on alcohol. Intracerebroventricular injections of ANP attenuated, whereas those of an antiserum against ANP intensified hyperexcitability during AW. ANP in the brain - the content of which undergoes sensitive changes in the hippocampus during AW appears to interact primarily with glutamate transmission through the NMDA-receptors. This brain structure is of utmost importance for the generation of withdrawal-related hyperexcitability. It is concluded that peripheral secretion of ANP might be a diagnostics indicator, whereas ANP in the CNS might be a modulator of AW.
长期饮酒突然戒断会产生一系列明确的症状，称为酒精戒断（AW）。尽管预测复杂的酒精戒断对于提前规划适当的治疗至关重要，但酒精戒断症状出现的确切病理生理机制，尤其是与震颤谵妄（DT）发作相关的机制，仍有待阐明。中枢神经系统（CNS）谷氨酸和γ-氨基丁酸传递的变化以及电压门控钙通道的作用，同样是对酒精长期存在的神经适应的重要因素。然而，除了中枢神经系统调节外，外周液体和电解质稳态的变化可能伴随酒精戒断，并预期会改变其临床症状。在急性戒断的早期阶段，心房利钠肽（ANP）的血浆水平、血浆肾素活性和醛固酮水平都很高。在患有震颤谵妄的患者中，在震颤谵妄实际发作前几天就观察到了心房利钠肽水平的升高。得出的结论是，血浆心房利钠肽分泌的改变可能与之相关，因此可作为震颤谵妄发作的指标。然而，心房利钠肽存在于大脑中并由大脑产生，因此它可被视为一种神经肽。在对酒精产生耐受性并产生身体依赖性的小鼠中研究了中枢神经系统心房利钠肽的作用。脑室内注射心房利钠肽可减轻酒精戒断期间的过度兴奋，而注射抗心房利钠肽抗血清则会加剧这种过度兴奋。大脑中的心房利钠肽——其含量在酒精戒断期间在海马体中发生敏感变化——似乎主要通过NMDA受体与谷氨酸传递相互作用。这个脑结构对于产生与戒断相关的过度兴奋至关重要。得出的结论是，外周心房利钠肽的分泌可能是一个诊断指标，而中枢神经系统中的心房利钠肽可能是酒精戒断的调节因子。
