Heinemeyer G
Clin Pharmacokinet. 1987 Jul;13(1):1-25. doi: 10.2165/00003088-198713010-00001.
Life-threatening increased intracranial pressure can be reversed by a variety of drugs. These compounds all have some disadvantages, producing rebound effects, severe coma or cardiovascular depression and electrolyte imbalance. However, reduction of intracranial pressure is a prerequisite for recovery and the benefits of treatment outweigh the risks. Dexamethasone is rapidly eliminated, the short half-life (about 3 hours) indicating that dosage intervals should be kept small. As yet, however, its therapeutic efficacy has not been clearly demonstrated. Therefore, an association between pharmacokinetics and pharmacodynamics cannot be established. Osmotic diuretics are the most widely used agents for reduction of intracranial pressure. Pharmacokinetics show a very close relationship to changes in serum osmolality, but there are large variations in the clearance. For the use of osmotics, the blood-brain barrier must be intact. Osmotic diuretics may lead to intracerebral oedema or to acute renal failure as serum osmolality increases. Considering the pharmacokinetics of each drug, and the dynamics of intracerebral pressure and osmolality, an intermittent, individually titrated dosage should be administered, with simultaneous monitoring of intracranial pressure. Frusemide (furosemide) can be used as an adjunct, to enhance the effect of osmotic diuretics. Its pharmacokinetics are limited by renal function, depending on age as well as on the extent of renal impairment. Altered renal elimination of concomitantly administered drugs, and electrolyte imbalances should be anticipated when diuretics are used. Barbiturates are certain to decrease intracranial pressure in humans by an as yet unknown mechanism. Their administration is recommended for patients that do not respond to conventional therapy. As barbiturates can result in deep coma, knowledge of their pharmacokinetics is of great importance for recovery. Following single doses, pentobarbitone has a relatively long elimination half-life (about 22 hours). However, after repeated administration for several days, its elimination may be enhanced due to autoinduction. Thiopentone kinetics are characterised by distribution and redistribution into deep peripheral compartments. Administration of high and frequent doses leads to considerably delayed recovery. This is not true for methohexitone, which shows comparable pharmacokinetics after single and multiple dose administration. Elimination depends on liver blood flow. Thus, recovery from methohexitone-coma is rapid. Rapid elimination is also an important characteristic of etomidate and alphaxalone/alphadolone, two non-barbiturate hypnotics.(ABSTRACT TRUNCATED AT 400 WORDS)
多种药物可逆转危及生命的颅内压升高。这些化合物都有一些缺点，会产生反跳效应、严重昏迷或心血管抑制以及电解质失衡。然而，降低颅内压是康复的前提，治疗的益处大于风险。地塞米松消除迅速，短半衰期（约3小时）表明给药间隔应保持较短。然而，其治疗效果尚未得到明确证实。因此，无法建立药代动力学与药效学之间的关联。渗透性利尿剂是降低颅内压最广泛使用的药物。药代动力学与血清渗透压的变化关系非常密切，但清除率存在很大差异。对于渗透性药物的使用，血脑屏障必须完整。随着血清渗透压升高，渗透性利尿剂可能导致脑水肿或急性肾衰竭。考虑到每种药物的药代动力学以及颅内压和渗透压的动态变化，应给予间歇性、个体化滴定剂量，并同时监测颅内压。呋塞米可作为辅助药物，增强渗透性利尿剂的效果。其药代动力学受肾功能限制，取决于年龄以及肾功能损害程度。使用利尿剂时，应预计到同时服用药物的肾脏清除改变以及电解质失衡。巴比妥类药物肯定会通过一种尚不清楚的机制降低人类颅内压。建议对常规治疗无反应的患者使用。由于巴比妥类药物可导致深度昏迷，了解其药代动力学对康复非常重要。单次给药后，戊巴比妥的消除半衰期相对较长（约22小时）。然而，连续给药数天后，由于自身诱导其消除可能会加快。硫喷妥钠的动力学特征是分布和再分布到深部外周隔室。高剂量和频繁给药会导致恢复明显延迟。甲己炔巴比妥并非如此，单次和多次给药后其药代动力学相当。消除取决于肝血流量。因此，甲己炔巴比妥昏迷后的恢复很快。快速消除也是依托咪酯和阿法沙龙/阿法多龙这两种非巴比妥类催眠药的重要特征。（摘要截选至400字）
