Drugs
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Prolonged-release mesalazine (Pentasa) consists of ethylcellulose-coated microgranules from which mesalazine (known in the US as mesalamine) is released in the small and large intestine in a diffusion-dependent manner. Dose-dependent improvements in clinical and endoscopic parameters have been reported with prolonged-release mesalazine 2 and 4 g/day in clinical trials in patients with mild to moderately active ulcerative colitis. Induction of clinical and endoscopic remission was achieved in more patients receiving a daily dosage of 4 g/day than in those receiving placebo. In patients with ulcerative colitis in remission, prolonged-release mesalazine is effective in reducing the rate of relapse. Higher dosages tend to be more effective, and a 12-month remission rate of 64% has been reported for patients treated with a 4 g daily dosage of this formulation. Comparative data indicate that prolonged-release mesalazine has similar efficacy in maintaining remission to molar equivalent doses of sulfasalazine. Data from a study in patients with mild to moderately active Crohn's disease indicates that higher dosages (4 g/day) of prolonged-release mesalazine are more effective than placebo in reducing disease activity. After 16 weeks' treatment, 64% of patients receiving a 4 g/day dosage experienced clinical improvement and 43% attained remission. In studies of patients in remission of Crohn's disease, the formulation appears to be more effective in preventing relapse in patients with isolated small bowel disease than in those with colonic involvement. The tolerability profile of oral prolonged-release mesalazine is similar to that of placebo and the incidence of adverse events does not appear to be dose-related. Nausea/vomiting, diarrhoea, abdominal pain and dyspepsia occur most frequently, although their incidence is low. Reports of nephrotoxicity during prolonged-release mesalazine treatment are rare. ⋯ Oral prolonged-release mesalazine is effective for maintenance and induction of remission of mild to moderately active colitis, both in patients with distal disease and in those with pancolitis. The formulation has similar efficacy to that of equimolar concentrations of sulfasalazine. Prolonged-release mesalazine also appears to be effective in the treatment of Crohn's disease, and maintenance therapy is of particular value in patients with isolated small bowel involvement. Evidence suggests that higher dosages (3 to 4 g/day) of prolonged-release mesalazine have additional therapeutic benefits over lower dosages in patients with inflammatory bowel disease without increasing the incidence of adverse events.
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Multiple sclerosis (MS) is considered an autoimmune disease associated with immune activity directed against central nervous system antigens. Based on this concept, immunosuppression and immunomodualtion have been the mainstays of therapeutic strategies in MS. During the last decade new therapies have been shown to significantly improve MS disease course. ⋯ Currently, there are new ongoing studies testing safety and/or efficacy of different combination regimens (i.e. azathioprine with IFNbeta, IFNbeta with glatiramer acetate, or pulses of intravenous cyclophosphamide with IFNbeta). Determining the effect of different therapies on the course of the disease within large clinical studies appears easier than determining individual responsiveness. Therefore, standardised methods for evaluating individual patients receiving disease-modifying therapies and development of effective therapeutic algorithms are needed.
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Based on findings that the cardiotoxicity infrequently observed with racemic bupivacaine shows enantioselectivity, i.e. it is more pronounced with the R(+)-enantiomer, the S(-)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic. The majority of in vitro, in vivo and human pharmacodynamic studies of nerve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicity than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75 mg, produced less prolongation of the QTc interval than bupivacaine. Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine. Levobupivacaine is long acting with a dose-dependent duration of anaesthesia. The onset of action is < or = 15 minutes with various anaesthetic techniques. In studies of surgical anaesthesia in adults, levobupivacaine provided sensory block for up to 9 hours after epidural administration of < or = 202.5 mg, 6.5 hours after intrathecal 15 mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blind clinical studies established that the anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those of bupivacaine at the same dose. Sensory block tended to be longer with levobupivacaine than bupivacaine, amounting to a difference of 23 to 45 minutes with epidural administration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block. Conditions satisfactory for surgery and good pain management were achieved by use of local infiltration or peribulbar administration of levobupivacaine. Levobupivacaine was generally as effective as bupivacaine for pain management during labour, and was effective for the management of postoperative pain, especially when combined with clonidine, morphine or fentanyl. The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. No clinically significant ECG abnormalities or serious CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%). ⋯ Levobupivacaine is a long acting local anaesthetic with a clinical profile closely resembling that of bupivacaine. However, current preclinical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are needed before the role of the drug can be fully established. Excluding pharmacoeconomic considerations, levobupivacaine is an appropriate choice for use in place of bupivacaine.
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Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with advanced (locally advanced or metastatic) breast cancer. Reported objective response rates for docetaxel 100 mg/m2 ranged from 54 to 69% and 53 to 82% as first-line monotherapy or combination therapy, respectively. Objective response rates of 23 to 65% and 30 to 81% have been reported for docetaxel as second-line monotherapy or combination therapy, respectively. In Japanese studies, second-line docetaxel 60 mg/m2 produced objective response rates of 42 to 55%. At the recommended dose of 100 mg/m2 given as a 1-hour intravenous (i.v.) infusion every 3 weeks, docetaxel had significantly greater efficacy than doxorubicin, mitomycin plus vinblastine and methotrexate plus fluorouracil, and similar efficacy to fluorouracil plus vinorelbine in pretreated patients with advanced breast cancer. In chemotherapy-naive patients, first-line combined therapy with docetaxel and doxorubicin had significantly greater efficacy than doxorubicin plus cyclophosphamide. Promising results have been achieved in phase I/II trials of a weekly regimen of docetaxel (generally 30 to 45 mg/m2). Preliminary data indicate a potential role for docetaxel in the neoadjuvant therapy of early breast cancer. The major dose-limiting adverse event associated with docetaxel is neutropenia. Although other adverse events are common, the tolerability profile of docetaxel is generally acceptable in the majority of patients, particularly in comparison with other antineoplastic regimens. ⋯ Although no single standard regimen has been identified as optimal for the treatment of advanced breast cancer, phase III trials have shown that docetaxel has improved efficacy over doxorubicin alone (considered one of the current gold standards), methotrexate/fluorouracil and mitomycin/vinblastine in second-line therapy. In combination with doxorubicin, docetaxel has demonstrated better efficacy than doxorubicin/cyclophosphamide in first-line therapy. These results provide a basis for therapy choice in advanced breast cancer. Clinical trials comparing docetaxel monotherapy versus paclitaxel monotherapy and versus docetaxel combination therapy are warranted. The role of docetaxel in the adjuvant and neoadjuvant treatment of early breast cancer is being evaluated.
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Pain, nausea and vomiting are frequently listed by patients as their most important perioperative concerns. With the change in emphasis from an inpatient to outpatient hospital and office-based medical/surgical environment, there has been increased interest in the 'big little problem' of postoperative nausea and vomiting (PONV). Currently, the overall incidence of PONV is estimated to be 25 to 30%, with severe, intractable PONV estimated to occur in approximately 0.18% of all patients undergoing surgery. ⋯ Combination antiemetic therapy improves efficacy for PONV prevention and treatment. In the difficult-to-treat PONV patient (as in the chemotherapy patient), suppression of numerous emetogenic peripheral stimuli and central neuroemetic receptors may be necessary. This multimodal PONV management approach includes use of: (i) multiple different antiemetic medications (double or triple combination antiemetic therapy acting at different neuroreceptor sites); (ii) less emetogenic anaesthesia techniques; (iii) adequate intravenous hydration; and (iv) adequate pain control.