Drugs of today
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Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess urate burden by regular use of drugs that reduce serum urate levels. Conventional urate-lowering drugs available in the U. ⋯ In recent clinical trials, pegloticase normalized plasma urate levels, reduced the size of tophi, and improved functional status and quality of life in patients with refractory disease. Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions. Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy.
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Neuromuscular blocking agents (NMBAs) are widely used to provide muscle relaxation for endotracheal intubation, certain modes of mechanical ventilation and surgical procedures. Full and rapid reversal of this muscle relaxation is needed to prevent residual muscle paralysis and respiratory compromise. The novel selective reversal binding agent, sugammadex, rapidly reverses muscle paralysis from steroidal NMBAs. ⋯ Unlike other reversal agents, sugammadex has the ability to provide fast and thorough reversal of neuromuscular paralysis regardless of the level of blockade. Sugammadex has shown limited adverse effects and avoids the cardiovascular and autonomic effects commonly seen with the conventional reversal of NMBAs (anticholinesterase plus anticholinergic). This review summarizes the current knowledge about sugammadex, its pharmacology and safety profile, dosing recommendations, potential clinical applications and economic impact.
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The administration of antibiotics by the inhaled route offers an appealing and logical approach to treating infectious respiratory conditions. Studies in the cystic fibrosis (CF) population have established the efficacy of this therapeutic concept and inhaled antibiotic therapy is now one of the pillars of management in CF. ⋯ Inhaled versions of ciprofloxacin have shown good tolerability and microbiological efficacy in preliminary studies, suggesting that effective inhaled antibiotics are finally on the horizon for this previously neglected patient population. The increased use of long-term inhaled antibiotics for a wider range of non-CF indications presents risks to the broader community of greater antimicrobial resistance development that must be carefully weighed against any demonstrated benefits.
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Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met). A range of tumors, including subsets of non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma and inflammatory myofibroblastic tumors harbor an ALK rearrangement that leads to oncogenic activation of ALK. Crizotinib has demonstrated preclinical and clinical activity against such malignancies through inhibition of ALK, and patients harboring ALK- rearranged NSCLC have demonstrated high response rates and prolonged progression-free survival in phase I and II studies. In August 2011, crizotinib was approved for the treatment of advanced ALK-positive NSCLC.
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The clinical outcome for patients with chronic myeloid leukemia in chronic phase (CML-CP) is currently very favorable due to the availability of tyrosine kinase inhibitors (TKIs) that are well tolerated and effectively suppress the constitutively activated BCR-ABL1 kinase that underlies the pathogenesis of this malignancy. Three TKIs -imatinib, nilotinib and dasatinib- have been approved as frontline therapy in CML-CP. Another TKI, bosutinib, inhibits with high potency numerous tyrosine kinases, including BCR-ABL1, Src family of kinases and MAPK, among others. ⋯ In patients with CML-CP with prior intolerance or resistance to imatinib therapy, bosutinib rendered response rates similar to those observed in the same patient population treated with nilotinib or dasatinib. Preliminary results from the ongoing phase III BELA study in which bosutinib is compared in a randomized fashion to imatinib for patients with newly diagnosed CML-CP have been recently reported. We herein summarize the preclinical and clinical experience of bosutinib in CML.