Drugs
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Chronic lymphocytic leukaemia (CLL) is a disease of late middle age and older. The majority of patients are diagnosed because of a lymphocytosis of at least 5 x 10(9)/L on an incidental blood count. It needs to be distinguished from mantle cell lymphoma and splenic marginal zone lymphoma by lymphocyte markers. ⋯ Only time will tell whether some of these patients are cured but it seems unlikely. Standard allogeneic bone marrow transplant is probably too hazardous for most patients, but non-myeloablative regimens hold out the hope of invoking a graft-versus-leukaemia effect without a high tumour-related mortality. Trials of immunotherapy are exciting options for a few patients in specialised centres.
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Stroke and its consequences are of global concern. Although stroke can affect individuals of any age, it primarily affects the elderly. It is among the leading causes of severe disability and mortality. ⋯ Although intravenous alteplase is recommended for any age beyond 18 years, elderly patients, in particular patients aged > or = 80 years, were often excluded or under-represented in randomised clinical trials of thrombolysis, so that available data on risk/benefit ratio for the very elderly are limited. Small post-marketing series suggest that despite elderly patients over 80 years having greater pre-stroke disability, the use of intravenous alteplase in this patient group does not significantly differ in effectiveness and complications compared with the same treatment in patients aged under age 80 years. Further studies are necessary and elderly patients with acute stroke should be included in future trials of the merits of thrombolytic therapy.
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Oseltamivir is a prodrug of oseltamivir carboxylate (Ro 64-0802, GS4071), a potent and selective inhibitor of the neuraminidase glycoprotein essential for replication of influenza A and B viruses. Studies in volunteers with experimental human influenza A or B showed that administration of oral oseltamivir 20 to 200 mg twice daily for 5 days reduced both the quantity and duration of viral shedding compared with placebo. Subsequent assessment of the drug at a dosage of 75 mg twice daily for 5 days in otherwise healthy adults with naturally acquired febrile influenza showed that oseltamivir reduced the duration of the disease by up to 1.5 days and the severity of illness by up to 38% compared with placebo when initiated within 36 hours of symptom onset (earlier initiation of therapy was associated with faster resolution). The incidence of secondary complications and the use of antibacterials were also reduced significantly in oseltamivir recipients. A liquid formulation of oseltamivir (2 mg/kg twice daily for 5 days) has been shown to be effective in the treatment of children with influenza, and data presented in abstracts suggest that the drug may also be of use in high-risk populations such as the elderly or those with chronic cardiac or respiratory disease. In addition to treatment efficacy, the drug has demonstrated efficacy when used for seasonal or household prophylaxis. Oral oseltamivir (75 mg once or twice daily for 6 weeks) during a period of local influenza activity significantly prevented the development of naturally acquired influenza by >70% compared with placebo in unvaccinated otherwise healthy adults. The drug also demonstrated efficacy when used adjunctively in previously vaccinated high-risk elderly patients (92% protective efficacy). Short term administration of oseltamivir (75 mg once daily for 7 days) may significantly reduce the risk of illness in household contacts of infected persons when administered within 48 hours of symptom onset in the infected person. Oseltamivir 75 mg twice daily for 5 days was well tolerated in clinical trials in healthy adults and high-risk patients, with nausea and vomiting being the most commonly reported events. Gastrointestinal events were mild and transient and both nausea and vomiting were less likely when oseltamivir was taken with food. ⋯ Oseltamivir is a well tolerated orally active neuraminidase inhibitor which significantly reduces the duration of symptomatic illness and hastens the return to normal levels of activity when initiated promptly in patients with naturally acquired influenza. It therefore represents a useful therapeutic alternative to zanamivir (especially in patients who prefer oral administration or who have an underlying respiratory disorder) and the M2 inhibitors amantadine and rimantadine (because of its broader spectrum of anti-influenza activity and lower likelihood of resistance) in patients with influenza. In addition, although annual vaccination remains the best means of influenza prevention, there may be a place for oseltamivir in providing household prophylaxis or adjunctive prophylaxis in high-risk vaccinated patients during an outbreak of the disease or for use in patients in whom vaccination is unsuitable or ineffective.
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Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. ⋯ Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.
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Rapacuronium bromide (rapacuronium; ORG-9487) is a nondepolarising muscle relaxant (NMBA) with a low potency [90% effective dose (ED90) 1 mg/kg], which to some extent is responsible for its rapid onset of action. Because of the high plasma clearance (5.3 to 11.1 mg/kg/min) of rapacuronium, its clinical duration of action following single bolus doses up to 2 mg/kg in adults is short (i.e. <20 minutes). Rapacuronium forms a pharmacologically active 3-desacetyl metabolite, ORG-9488, which may contribute to a delay in spontaneous recovery after repeat bolus doses or infusions. ⋯ Like atracurium, cisatracurium undergoes Hofmann elimination. In contrast to atracurium, cisatracurium does not undergo hydrolysis by nonspecific plasma esterases. Moreover, about 77% of the drug is cleared by organ-dependent mechanisms.