Cns Drugs
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Propofol (Diprivan) is a phenolic derivative with sedative and hypnotic properties but is unrelated to other sedative/hypnotic agents. Formulated as an oil-in-water emulsion for intravenous use, it is highly lipophilic and rapidly crosses the blood-brain barrier resulting in a rapid onset of action. Emergence from sedation is also rapid because of a fast redistribution into peripheral tissues and metabolic clearance. The depth of sedation increases in a dose-dependent manner. In well designed clinical trials in patients receiving sedation in the intensive care unit (ICU) for a variety of indications, propofol provided adequate sedation for a similar proportion of time to midazolam, but the rate of recovery was faster with propofol. Even after periods of prolonged sedation (>72 hours), propofol was generally associated with a faster time to recovery than midazolam. Propofol facilitated better predictability of recovery and an improved control of the depth of sedation in response to titration than midazolam. In patients sedated following head trauma, propofol reduced or maintained intracranial pressure. Propofol is associated with generally good haemodynamic stability but induces a dose-dependent decrease in blood pressure and heart rate. Bolus administration may cause transient hypotension, and slow initial infusions are recommended in most patients. Serum triglyceride concentrations should be monitored during prolonged infusions (>3 days) because of the risk of hypertriglyceridaemia. The administration of 2% propofol can reduce this risk. Strict aseptic technique must be used during the handling of the product to prevent accidental extrinsic microbial contamination. Despite a higher acquisition cost with propofol, most studies of short-term sedation (approximately <3 days) showed that overall costs were lower with propofol than with midazolam, because a faster time to extubation reduced total ICU costs. However, as the period of sedation increased, the cost difference decreased. ⋯ The efficacy of propofol in the sedation of adults in the ICU is well established, and clinical trials have demonstrated a similar quality of sedation to midazolam. Because of a rapid distribution and clearance, the duration of action of propofol is short and recovery is rapid. Emergence from sedation is more rapid with propofol than with midazolam, even after long-term administration (>72 hours), which enables better control of the depth of sedation in response to titration and more predictable recovery times. Thus, for the ICU sedation of adults in a variety of clinical settings, propofol provides effective sedation with a more rapid and predictable emergence time than midazolam.
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Total intravenous anaesthesia (TIVA) has many advocates and offers potential benefits, yet the direct costs of this technique are commonly greater than those of inhalation-based alternatives. Although many advantages are claimed for TIVA, in reality all modern anaesthetics are effective and have good safety and tolerability profiles, rendering these differences of less importance now than was perhaps once the case. The majority of direct comparisons between inhaled and intravenous anaesthetics have failed to demonstrate significant differences in recovery times, yet they have consistently shown greater direct costs associated with intravenous propofol anaesthesia. ⋯ Nevertheless, the net result of lowered costs is that all types of anaesthetic drugs, which typically comprise <5% of a hospital pharmacy budget, represent excellent value for money. With few new products in the immediate pipeline and most established drugs already generic or about to lose their patent protection, the expense of anaesthesia is likely to decline even further. Perhaps then we will be able to stop arguing over relatively small differences in cost and choose a technique that, in our own experienced hands, provides the best and safest patient outcomes.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Speed of onset and efficacy of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled, dose-ranging study versus zolmitriptan tablet.
Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of zolmitriptan administered via a nasal spray with placebo and zolmitriptan oral tablet in the acute treatment of migraine. ⋯ All doses of zolmitriptan nasal spray produced significant 2-hour headache response rates compared with placebo. The 5.0 and 2.5mg doses were also significantly more effective than placebo for the majority of secondary efficacy measures. Zolmitriptan nasal spray 5.0mg provided a headache response statistically superior to both placebo and the 2.5mg tablet as early as 15 minutes after administration, while demonstrating pain-free outcomes significantly superior to placebo and the 2.5mg tablet as early as 30 minutes after administration. All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.
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In <25 years, intrathecal administration of opioids (i.e. spinal analgesia) has evolved from an experimental model into an important therapy for obstetric analgesia and anaesthesia. A small dose of opioid delivered into the CSF provides almost immediate relief from labour pain with minimal risks to the mother and fetus. Careful attention, and prompt treatment when needed, can ameliorate the adverse effects of fetal bradycardia, respiratory depression and pruritus. ⋯ Controversy revolves around the incidence of fetal bradycardia following CSE and whether this phenomenon increases the rate of operative deliveries. The rapid onset of analgesia with intrathecally administered opioids must be balanced against the added risks of dural puncture and considered in the context of the whole duration of labour. Ultimately, the decision to choose a CSE technique depends on the experience of the anaesthesia provider and the local availability of drugs, equipment and monitoring capabilities.