International journal of clinical practice. Supplement最新文献

Buprenorphine is an opioid analgesic, derived from thebaine. Buprenorphine was initially classified as a "mixed agonist-antagonist analgesic" or a narcotic antagonist analgesic. The work of Martin et al (1976) on the animal model of the chronic spinal dog substantiated the substance's action as partial agonist at the mu-opioid receptor. These findings were underscored by the substance's general pharmacological profile. Further, buprenorphine was one of the first narcotic analgesics to be assessed for its abuse liability in humans. The lower abuse liability of the drug in humans soon turned it into a widely used therapeutic agent in patients with opioid dependence. Interest in buprenorphine spanning more than 30 years has been attributed to its unique pharmacological characteristics, including moderate intrinsic activity, high affinity to and slow dissociation from mu-opioid receptors. Early pharmacological studies demonstrated buprenorphine's strong binding to opioid receptors, and an inverted U-shaped dose-response curve in rodents. In the rat paw formalin test, although buprenorphine demonstrated a bell-shaped dose-response curve against an acute noxious stimulus, it showed a classic sigmoidal curve in the later phase of the assay. In most preclinical antinociceptive tests, buprenorphine was shown to be fully efficacious, with an antinociceptive potency 25 to 40 times higher than morphine. A ceiling effect for respiratory depression (but not for analgesia) has been demonstrated in humans. Current studies are focusing on norbuprenorphine, an N-dealkylated metabolite of buprenorphine. Norbuprenorphine is a likely contributor to the overall pharmacology of buprenorphine; in the mouse writhing test, norbuprenorphine provides antinociceptive efficacy similar to buprenorphine, with analgesic activity shown to be dose-dependent.

A system for the transdermal administration of the opioid drug buprenorphine has recently been introduced. Buprenorphine has physico-chemical properties, including a low molecular weight and high analgesic potency, that make it an excellent compound for transdermal drug delivery. The new technology (buprenorphine TDS, Transtec) is an advanced system that contains the active drug incorporated into a polymer matrix, which is at the same time the adhesive layer. The patch precisely controls the rate of drug delivery and produces stable plasma concentrations. It is available in three doses (release rates of 35, 52.5 and 70 microg/h), and the suggested duration of use per patch is three days. Buprenorphine TDS was developed for the treatment of moderate to severe cancer pain and severe pain which does not respond to non-opioid analgesics. Not only does this transdermal system provide excellent analgesia and a low incidence of adverse events, but its ease of use results in greater compliance. The patch provides excellent adhesion and has a low susceptibility to damage that might lead to toxicity or opioid abuse.

Recent advances in therapy for multiple sclerosis (MS) have centred on the use of the disease-modifying drugs glatiramer acetate (GA) and interferon (IFN) beta. Several large-scale clinical trials have been carried out on the use of these compounds, but there have been few studies that have directly compared their efficacy in MS. Furthermore, there has been controversy and confusion over the IFN beta therapy regimen that will achieve the best possible clinical outcome for MS patients. This review focuses principally on clinical trials of IFN beta-1a, where data that allow direct comparison of different treatment regimens are now available. Current data indicate that IFN beta, and in particular IFN beta-1a, has important advantages over GA in the treatment of relapsing-remitting MS (RRMS). Additionally, IFN beta-1a (Rebif, Serono), 44 microg administered subcutaneously (s.c.) three times weekly (t.i.w.), is significantly more effective than IFN beta-1a (Avonex, Biogen), 30 microg administered intramuscularly once weekly. For optimal management of RRMS, treatment with IFN beta-1a, 44 microg s.c. t.i.w., should begin as early as possible after diagnosis.

Therapy with interferon (IFN) beta can significantly alter the disease course in relapsing-remitting multiple sclerosis. Evidence indicates that the efficacy of this agent is related to treatment regimen (dose, route and dose frequency). A higher total weekly dose administered several times a week provides greater clinical benefit than a lower dose given once weekly (q.w.). This dose- and dose frequency-dependency of the efficacy of IFN beta has been clearly demonstrated in three recent head-to-head studies, as well as in other major clinical trials, and pharmacodynamic, pharmacokinetic and pre-clinical studies. The use of a q.w. dose regimen of IFN beta is likely to have a negative impact on patients in both the short and long-term because it allows additional accumulation of irreversible tissue damage in the central nervous system. Patients should receive the optimal, more rapid benefits from higher and more frequent doses of IFN beta, administered as early as possible after diagnosis.

In recent years, major advances have been made in the management of multiple sclerosis (MS) in the form of new disease-modifying therapies, the most widely used of which is interferon (IFN) beta. A growing body of evidence indicates that the beneficial effects of IFN beta are maximised if treatment is started as soon as possible after the diagnosis of MS, and if patients are given the highest possible dose. The argument in favour of early treatment is based primarily on the finding that the inflammation of the central nervous system characteristic of MS leads to irreversible axonal destruction starting very early in the course of the disease. Evidence that IFN beta should be given at high doses comes from preclinical and clinical studies showing that the effects of this drug are strongly dose-dependent. Three formulations of IFN beta are currently available for the treatment of MS: subcutaneous (s.c.) IFN beta-1a, intramuscular (i.m.) IFN beta-1a and s.c. IFN beta-1b. All are well tolerated, although IFN beta-1a appears to be less immunogenic than IFN beta-1b. IFN beta-1a, in s.c. formulation, has advantages over the other formulations in terms of convenience, and is approved for use at higher doses than i.m. IFN beta-1a.