Drugs of today
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The pharmacologic management of type 2 diabetes has changed dramatically in the past two decades. We have moved from a situation of only having two choices, insulin and sulfonylureas, to a position of myriad choices from 11 categories of medications (insulin, sulfonylureas, biguanides, α-glucosidase inhibitors, gliptins (dipeptidyl peptidase 4 [DPP IV] inhibitors), bromocriptine, glucagon-like peptide analogues, thiazolidinediones, glinides, amylin analogues and bile acid sequestrants. One of the most recent additions to this list are the DPP IV inhibitors commonly known as gliptins. ⋯ This manuscript will review alogliptin, its chemistry, pharmacokinetics/pharmacodynamics, drug interactions, clinical trials and its current state of FDA review. Preclinical animal data have been reviewed elsewhere and will not be outlined in this manuscript. The interested reader is referred to those recent reviews (4, 5).
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As B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), therapies targeting them may provide a valuable treatment for patients with SLE. One of the therapeutic strategies for B-cell targeting is through the inhibition of factors involved in the survival or differentiation of B cells. B-cell-activating factor (BAFF) or B-lymphocyte stimulator (BlyS; trademark of Human Genome Sciences, Rockville, MD, USA) has proven to be a key factor in the selection and survival of B cells. ⋯ To date, two phase III trials have demonstrated that belimumab in combination with standard of care significantly reduced SLE disease activity and SLE flare rates in patients with active SLE. In addition, it was generally well tolerated. This article reviews the immune mechanisms induced by the inhibition of BAFF/BLyS and the evidence-based clinical effectiveness of belimumab in SLE patients.
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Management of central nervous system (CNS) malignancies continues to be a therapeutic challenge. Both primary and secondary (metastatic) CNS tumors are frequently resistant to commonly used chemotherapeutic agents. Surgery and radiotherapy provide palliation of symptoms but usually do not lead to curative outcomes. ⋯ Temozolomide offers improved outcomes when used alone or in combination with irradiation. Its role in the therapy of other types of brain cancer, and specifically primary CNS lymphoma, continues to develop. This review will discuss the early stages of development of temozolomide, its introduction into the therapy of glioma, its role in the therapy of elderly patients, mechanisms of resistance and the evolution of its current and future applications.
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A large anticancer armamentarium is available for treating patients with solid and hematological malignancies, but currently available therapies for cancer have many limitations in terms of curing the disease. Fighting for new therapies is thus essential, as is getting first-hand information on new therapies as they become available. The annual meeting of the American Society of Clinical Oncology (ASCO) helps serve that purpose by spreading knowledge on new treatments and new targets for intervention. To supplement ASCO's efforts and for the benefit of our users and readers, this report will offer a glimpse of what this year's meeting was like, giving special attention to currently available therapies and investigational drugs in development, the anticancer activity of which was reported during the meeting in Chicago.
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Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a dismal prognosis for which, until recently, there were no effective treatments. Pirfenidone (5-methyl-1-phenylpyridin-2[1H]-one) is a novel antifibrotic agent that has been demonstrated to slow disease progression in patients with IPF. In vitro and in vivo animal models of pulmonary fibrosis have shown that pirfenidone exerts its effect by reducing inflammatory cytokines such as TNF-α, by downregulating the transcription of key profibrotic growth factors including TGF-ß, and through reductions in lipid peroxidation and oxidative stress. ⋯ Reported adverse effects include nausea, anorexia and photosensitivity dermatitis. A number of questions remain concerning the long-term efficacy and safety of pirfenidone and whether slowing of lung function decline will translate into improved survival for patients with IPF. These questions notwithstanding, pirfenidone represents an important development in the treatment of IPF and is a much needed addition to the previously inadequate therapeutic armamentarium for this devastating disease.