Cns Drugs
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Review
Clinical potential of intra-arterial thrombolytic therapy in patients with acute ischaemic stroke.
Acute ischaemic stroke is a leading cause of mortality and morbidity around the world. An arterial occlusive lesion is found in the majority of patients with acute ischaemic stroke, and recanalisation has been shown to result in a better clinical outcome. The only widely approved recanalisation strategy is the use of intravenous alteplase (recombinant tissue-type plasminogen activator; tPA) within 3 hours of stroke onset. ⋯ The clinical benefits of intra-arterial pro-urokinase were recently proven in a randomised, placebo-controlled study. Third-generation agents, such as reteplase, lanoteplase and tenecteplase, offer superior recanalisation rates with limited systemic adverse effects and might prove to be the agents of choice for intra-arterial acute stroke thrombolysis in the future. The exact administration regimens as well as the identification of patient sub-populations most likely to benefit from intra-arterial thrombolysis are subjects of current investigations, and hopefully firmer guidelines will be established in the next few years, once the results of the clinical trials are available.
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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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Gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA) approved for use in adults with postherpetic neuralgia. Gabapentin does not bind to GABA(A) or GABA(B) receptors. Its mechanism of action in humans is unclear, but may involve binding to alpha2delta calcium channel subunits in animal models. ⋯ The proportion of responders (patients showing a > or =50% reduction in mean daily pain score at endpoint versus baseline) was significantly greater with gabapentin than placebo. Daily sleep rating scores, the Short Form McGill Pain Questionnaire (total pain scores), Patient and Clinician Global Impression of Change and measures on the Short Form-36 Health Survey (including physical functioning, role-physical, bodily pain, vitality or mental health) improved to a significantly greater extent with gabapentin than placebo. Adverse events associated with gabapentin in patients with postherpetic neuralgia were usually mild to moderate in intensity, with dizziness, somnolence and peripheral oedema being commonly reported.
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Baclofen, tizanidine and botulinum toxin A, agents used to treat disorders of muscle tone, have been studied as potential preventative treatments for migraine, tension-type headache and other related disorders. The most extensive work has been completed with botulinum toxin A. However, there is still a paucity of well controlled, clinical trials with this agent, and overall there have been conflicting and oftentimes equivocal results: studies of its use in migraine headache have suggested efficacy, whereas those of tension-type headache have not shown significant evidence of efficacy. ⋯ One well controlled trial, conducted as a follow-up to an open-label trial in the preventive treatment of chronic daily headache, reported tizanidine as having a statistically significant benefit over placebo. Also of interest is its use in conjunction with a long-acting NSAID to aid in the treatment of rebound headache accompanying the discontinuation of overused acute migraine therapies. In conclusion, though limited, the studies suggest the efficacy of botulinum toxin A, baclofen and tizanidine in primary headache disorders.