Drugs
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Review
Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer.
Trabectedin (Yondelis); ET-743) is an antineoplastic agent that was originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and is now produced synthetically. It binds to the minor groove of DNA, disrupting the cell cycle and inhibiting cell proliferation. Intravenous trabectedin administered once every 3 weeks is approved as monotherapy in Europe for use in patients with advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines or ifosfamide, or who are unsuited to receive these agents. ⋯ In clinical trials, trabectedin showed efficacy in the treatment of patients with advanced or metastatic STS, especially those with leiomyosarcoma or liposarcoma, as well as in women with platinum-sensitive advanced or recurrent ovarian cancer. In addition, its tolerability profile was generally manageable. The introduction of trabectedin expands the currently limited range of effective treatment options for patients with advanced or metastatic STS; trabectedin also has the potential to be a beneficial treatment for advanced or recurrent ovarian cancer.
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Abdominal cramping and pain is a frequent problem in the adult population of Western countries, with an estimated prevalence of < or =30%. Hyoscine butylbromide (scopolamine butylbromide) [Buscopan/Buscapina] is an antispasmodic drug indicated for the treatment of abdominal pain associated with cramps induced by gastrointestinal (GI) spasms. It was first registered in Germany in 1951 and marketed in 1952, and has since become available worldwide both as a prescription drug and as an over-the-counter medicine in many countries. ⋯ Hyoscine butylbromide is barely absorbed and detectable in the blood and does not penetrate the blood-brain barrier, and is, therefore, generally well tolerated. Few adverse events have been reported; in particular, no significant increases in the incidence of anticholinergic-related adverse effects have been observed. In summary, hyoscine butylbromide appears to be a valuable treatment option for patients with symptoms of abdominal pain or discomfort associated with cramping.
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Pruritus occurs frequently following opioid use, particularly after neuraxial administration. Although not life threatening, pruritus is discomforting and may decrease patient satisfaction. Even though the mechanism of opioid-induced pruritus is not yet fully understood, there is increasing evidence of the important role played by micro opioid receptors. ⋯ Of these, micro opioid receptor antagonists have been most consistent in terms of attenuating opioid-induced pruritus but present problems in dose and administration. Other drugs, including mixed opioid receptor agonist-antagonists, serotonin 5-HT(3) receptor antagonists, propofol, NSAIDs and D(2) receptor antagonists, have also been demonstrated to be useful. This review summarises the current understanding of the mechanisms causing opioid-induced pruritus and the pharmacological therapies available to prevent and/or manage this disorder.
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The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. ⋯ The unique antimicrobial spectrum and pharmacokinetic properties of ertapenem make it more suited to treatment of community-acquired infections and outpatient intravenous antimicrobial therapy than for the treatment of nosocomial infections. Doripenem is a promising new carbapenem with similar properties to those of meropenem, although it appears to have more potent in vitro activity against P. aeruginosa than meropenem. Clinical trials are required to establish the efficacy and safety of doripenem in moderate to severe infections, including nosocomial infections.
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The use of thalidomide is limited by adverse effects of sedation, constipation, neuropathy and thromboembolism. In order to discover more potent and less toxic immunomodulators than thalidomide, its chemical structure was modified and lenalidomide was formed. Lenalidomide is approved by the US FDA for the treatment of patients with low-risk myelodysplastic syndrome (MDS) with deletion 5q cytogenetic abnormality. ⋯ Significant risk of myelosuppression may lead to dose reduction in the majority of these patients. Clinical trials of relapsed and refractory MM have shown that lenalidomide is clinically efficacious at a dosage of 25 mg/day when administered in combination with dexamethasone. Lenalidomide should be continued until disease progression in both MDS and MM patients.