摘要：

Synopsis: Flunitrazepam 1 is a benzodiazepine derivative whose hypnotic effect predominates over the sedative, anxiolytic, muscle-relaxing and anticonvulsant effects characteristic of benzodiazepines. Thus, it is used as a night-time hypnotic and in anaesthesiology; due to the pronounced hypnotic effect it is not appropriate as a daytime sedative. Asa hypnotic for insomnia its effect is usually characterised by a very fast onset of action and quiet sleep without interruptions. On the morning after a hypnotic dose some residual psychomotor impairment does occur, which is comparable to that with usual doses ofnitrazepam or flurazepam, but clinically apparent 'hangover' occurs infrequently.There is no pronounced cumulative effect with chronic use. In anaesthesiology it has proven to be useful as a hypnotic on the night before operation, as an oral, intramuscular or intravenous premedication, in induction and as a supplement to other anaesthetics. Its sedative and amnesic properties can also be beneficial in intensive care patients. Much of the usefulness of flunitrazepam in anaesthesia relates to its synergistic effect with other anaesthetics, to its effective amnesic action and its acceptable effects on circulation and respiration. Possible drawbacks include a somewhat unusual course of induction (when used for this purpose) and an often prolonged recovery. Although the safe dosage range is wide with flunitrazepam, its effective application both as a hypnotic for insomnia and in anaesthesiology is dependent upon use of the optimal dosage, and adequate knowledge of its pharmacokinetic properties. Pharmacodynamic Studies : Flunitrazepam, like other benzodiazepines, has a selective effect on GABA (gamma-aminobutyric-acid)-mediated synaptic processes of the brain. Facilitation of the inhibitory effect of GABAergic synaptic transmission especially affects the limbic system. (The highly selective and saturable synaptic inhibition of GABA-mediated activities is accepted as the basis of the extraordinary safety range of benzodiazepines.) The different affinity of various benzodiazepines to specific benzodiazepine receptors correlates well with their pharmacological and therapeutic potencies. The relative weight-for-weight potency of flunitrazepam is high, on an average about 10 times as potent as diazepam; however, there is wide variation in this potency coefficient for different effects. Flunitrazepam produces a dose- and time-dependent amnesic effect, which is more complete and somewhat longer than the amnesia after diazepam, but clearly less intense and shorter than that produced by lorazepam. This amnesic effect is an important characteristic of flunitrazepam's use in different anaesthesia techniques, as it prevents patients from having unpleasant experiences during different stages of anaesthesia and operation. The most typical feature of flunitrazepam on the cardiovascular system is peripheral vasodilatation. This is possibly due to its direct relaxing effect on the muscle fibres in the vascular wall. A decrease in cardiac output also occurs, which is more pronounced in patients with cardiovascular disease. This effect, together with a marked decrease in peripheral resistance, results in a significant reduction of systolic blood pressure. The primary phenomenon may be limited to this peripheral vasodilatation, with a secondary decrease in venous return. This emphasises the importance of normal blood volume and active fluid infusion when flunitrazepam is used intravenously. Flunitrazepam has a depressive influence on respiration, even in small intravenous doses, and this effect is augmented by simultaneously administered analgesics or hypnotics. In occasional extreme cases there may be need for respiratory assistance. The effect on respiration results in a significant decrease in arterial oxygen tension; this may be corrected by increasing oxygen concentration in the inspired air. Pharmacokinetic Studies : Knowledge of the pharmacokinetic behaviour of flunitrazepam is extremely important for optimum practical use of t

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