摘要:

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. It is commonly believed that indirect costs may be offset by indirect savings achieved through more rapid recovery, reduction in adverse effects and decreased staff workloads. In some cases, these differences in outcome have not been observed, while in many where they have, indirect savings are only theoretical. Reductions in recovery time and nursing workload will only result in savings if fewer nurses are required or if the existing ones can be paid for fewer hours. Salary arrangements, peak demand for patient care, performance of multiple tasks in parallel and limitations in time accounting methodology all limit the ability to achieve such savings in reality.Drug wastage also contributes to the cost of anaesthesia and is common to both intravenous and inhaled techniques. With inhaled anaesthesia, wastage can be reduced by the use of lower fresh gas flows, which has no adverse consequences and may provide potential benefits. With intravenous anaesthesia, reducing drug wastage is difficult and potentially harmful through cross-contamination of drugs between patients.Recently, the cost of propofol has been reduced with the availability of generics, making TIVA a more attractive proposition. The costs of several inhaled anaesthetics have also decreased, however, reducing any relative benefit. 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.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Successful pharmacological treatment of pain in terminally ill patients is possible most of the time. It requires a determination of the type of pain syndrome (i.e. nociceptive, neuropathic or mixed). Complete pain assessment also requires an understanding of other dimensions of suffering that a patient may be experiencing on psychological, social and spiritual/existential levels.The World Health Organization has introduced a three-step approach to treating pain. Opioids are the mainstay of therapy for moderate to severe pain at the end of life. Familiarity with the pharmacokinetics, equianalgesic dose and adverse effects of opioids is necessary for their safe and effective use. In addition, adjuvant analgesics such as antiepileptic drugs, antidepressants and local anaesthetics are often needed to optimise pain control, especially in patients with neuropathic pain. Given the complex aetiology of pain states, combinations of classes of adjuvants may sometimes be needed for effective treatment.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Thirty-five years since its introduction into clinical use, valproate (valproic acid) has established itself as one of the most widely used antiepileptic drugs (AEDs). In recent years, there has been a growing awareness of the potential aggravation of seizure disorders by AEDs. Such aggravation may be due to a variety of factors that include a paradoxical pharmacodynamic effect. In order to address this important safety aspect of AED treatment, we reviewed all available published evidence in search of factors related to seizure aggravation during valproate therapy.We analysed the 20 available publications, which outline about 99 case reports (in some papers, the exact number was not specified) of aggravation of seizures associated with valproate. Almost all of these cases occurred in a specific clinical context known to be linked to seizure aggravation, such as overdose, encephalopathy, hepatopathy or metabolic disorders. However, we found no consistent evidence of pure pharmacodynamic aggravation in the absence of any of the above quoted factors.In view of the large number of patients treated worldwide with valproate, the number of reported cases of seizure aggravation in patients taking the drug in the literature is low. Conditions in which worsening of seizures as a result of valproate use may occur are well known and often avoidable. Thus, unlike most AEDs, including the newer ones, valproate appears to have a very low potential for pharmacodynamic paradoxical seizure aggravation. This knowledge is in accordance with long-standing clinical experience and practice.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Alzheimer’s disease affects nearly 5 million Americans currently and, as a result of the baby boomer cohort, is predicted to affect 14 million Americans and 22 million persons totally worldwide in just a few decades. Alzheimer’s disease is present in nearly half of individuals aged 85 years.The main symptom of Alzheimer’s disease is a gradual loss of cognitive function. Glutamatergic neurotransmission, an important process in learning and memory, is severely disrupted in patients with Alzheimer’s disease. Loss of glutamatergic function in Alzheimer’s disease may be related to the increase in oxidative stress associated with the amyloid β-peptide that is found in the brains of individuals who have the disease. Therefore, therapeutic strategies directed at the glutamatergic system may hold promise. Therapies addressing oxidative stress induced by hyperactivity of glutamate receptors include supplementation with estrogen and antioxidants such as tocopherol (vitamin E) and acetylcysteine (N-acetylcysteine). Therapy for hypoactivity of glutamate receptors is aimed at inducing the NMDA receptor with glycine and cycloserine (D-cycloserine). Recently, memantine, an NMDA receptor antagonist that addresses the hyperactivity of these receptors, has been approved in some countries for use in Alzheimer’s disease.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

ObjectiveZolmitriptan 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.Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs.All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.Patients and study designThis was a randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multicentre, dose-ranging study. 1547 patients aged 18–65 years with an established diagnosis of migraine with or without aura (as defined by International Headache Society criteria) who had at least a 1-year history of migraine and an age of onset <50 years were included. Patients were able to distinguish typical migraine from nonmigraine headaches and had experienced an average of one to six migraine headaches per month during the 2 months preceding the study. Patients were randomised to zolmitriptan (Zomig®1) nasal spray (5.0, 2.5, 1.0 or 0.5mg), zolmitriptan oral tablet (2.5mg) or placebo for the treatment of three moderate or severe migraine attacks. The primary outcome measure was headache response at 2 hours following treatment, defined as reduced intensity of migraine pain (using a scale of none, mild, moderate or severe) from severe or moderate at baseline to mild or no pain at 2 hours after treatment. Secondary outcome measures included early headache response at 15, 30 and 45 minutes and headache response at 1 and 4 hours postdose, as well as pain-free rates at 15, 30 and 45 minutes and 1, 2 and 4 hours postdose. Laboratory assessments, vital signs, 12-lead ECGs and nose and throat examinations were performed at screening and follow-up visits. Adverse events were recorded throughout the study using Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) terminology.Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs.All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.ResultsEach dose of zolmitriptan nasal spray produced a greater 2-hour headache response rate than placebo (70.3%, 58.6%, 54.8% and 41.5% for zolmitriptan nasal spray 5.0, 2.5, 1.0 and 0.5mg, compared with 30.6% for placebo [all p < 0.001 vs placebo]). The 2-hour headache response rate for zolmitriptan nasal spray 5.0mg was significantly higher than that of the zolmitriptan 2.5mg oral tablet (61.3%; p < 0.05), while comparisons of nasal spray 0.5, 1.0 and 2.5mg with zolmitriptan 2.5mg oral tablet were not statistically significant. The nasal spray 5.0 and 2.5mg showed a rapid onset of action, with a significant difference in headache response compared with placebo from 15 minutes through 4 hours after administration and a significant difference between the nasal spray 5.0mg and 2.5mg oral tablet from 15 minutes through to 2 hours (the other nasal spray doses were not statistically significant compared with 2.5mg oral tablet). Zolmitriptan nasal spray resulted in pain-free rates that were dose dependent. While all doses from 1.0mg upwards produced significant pain-free outcomes from 30 minutes versus placebo, only the 5.0mg dose produced pain-free rates significantly superior to both placebo and the 2.5mg oral tablet.Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs.All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.ConclusionAll 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.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

▴ SLI-381 is an extended-release formulation of short-acting Adderall®, a racemic mixture of dextro- and levo-isomers of amphetamine salts. Drug-containing microbeads within the SLI-381 capsule give a double-pulsed delivery, similar to that achieved by two equal doses of the short-acting formulation administered 4 hours apart.▴ In an intent-to-treat  analysis  of a 3-week, double-blind study in 563 children with attention-deficit hyperactivity disorder (ADHD), SLI-381 10, 20 or 30mg once daily improved mean morning and afternoon behaviour scores compared with baseline significantly more than placebo (p < 0.001 for all comparisons), as assessed by the Connors Global Index Scale for teachers (CGIS-T). Following treatment, CGIS-T scores were similar to those reported in children without ADHD.▴ In the same study, a dose-response relationship was observed, and increasing the dosage of SLI-381 by 10mg at weekly intervals, to a maximum of 30mg once daily, resulted in further improvements in the scores of the CGIS-T.▴ After early morning administration of SLI-381 in this double-blind study, late-afternoon scores of the CGIS for parents were similar to morning scores.▴ SLI-381 was generally well tolerated in randomised trials in children with ADHD for up to 24 months. Overall, adverse events were mild to moderate in intensity.Table. Features and properties of SLI-381 (Adderall XR®)

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The management of neurological and psychiatric disorders is a vast and evolving area for researchers, primary care physicians and specialists. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy for neurological and psychiatric disorders, this section of the journal brings you information selected from the drug therapy reporting serviceInpharma Weekly1. The following reports are selected from the latest issues, summarising the most important research and development news, clinical studies, treatment guidelines, pharmacological, pharmacoeconomic and adverse drug reactions/interactions news, and expert opinion pieces published across a broad range of literature sources.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS