Drugs
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Sudden unexpected deaths have been reported with antipsychotic use since the early 1960s. In some cases the antipsychotic may be unrelated to death, but in others it appears to be a causal factor. Antipsychotics can cause sudden death by several mechanisms, but particular interest has centred on torsade de pointes (TdP), a polymorphic ventricular arrhythmia that can progress to ventricular fibrillation and sudden death. ⋯ The risk should be viewed in the context of the overall risks and benefits of antipsychotic treatment. It seems prudent, where possible, to select antipsychotics that are not associated with marked QTc prolongation. If use of a QTc-prolonging drug is warranted, then measures to reduce the risk should be adopted.
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Review Comparative Study
Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis.
Etanercept is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. ⋯ In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.
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Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2 to 4%). ⋯ Rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest rizatriptan should be considered as a first-line treatment option in the management of migraine.
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Drotrecogin alfa (activated), recombinant human activated protein C, inhibits coagulation and inflammation and promotes fibrinolysis in patients with severe sepsis. 850 patients with severe sepsis treated with intravenous drotrecogin alfa (activated) 24 microg/kg/h for 96 hours had a significantly greater reduction in 28-day all-cause mortality (24.7%) than 840 placebo recipients (30.8%) in a randomised, double-blind, placebo-controlled study. The drug was associated with a 19.4% reduction in the relative risk of death at 28 days compared with placebo. Baseline characteristics of and pre-existing conditions in patients with sepsis appeared to have no effect on the efficacy of drotrecogin alfa (activated). ⋯ The most frequent site of bleeding was the gastrointestinal tract. With the exception of bleeding events, there were no clinically significant differences between treatment groups in the efficacy trial in the incidence of adverse events. Of the 210 deaths in patients with severe sepsis treated with drotrecogin alfa (activated) 24 microg/kg/h in the efficacy trial, four deaths due to haemorrhage and one due to cerebral oedema were possibly related to the study drug.
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Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient, and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. ⋯ Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (