Drugs of today
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Lower respiratory tract infections are usually treated with systemic antibiotics, but sometimes in certain conditions inhaled antibiotics may also be used. In cystic fibrosis (CF) for example, inhaled tobramycin is used to treat chronic airways infection due to Pseudomonas aeruginosa, and in other conditions such as ventilator-associated pneumonia, inhaled colistin is used as add-on therapy to reduce the risk of side effects of prolonged systemic exposure. Other inhaled antibiotics are currently under development, and inhaled amikacin is one such example. The two formulations of inhaled amikacin currently under clinical development may have two different therapeutic trajectories: the nebulized liposomal formulation is the first once-daily aminoglycoside for CF patients, whereas the free nebulized amikacin may be used in addition to systemic therapy in ventilator-associated pneumonia patients exploiting reduced systemic exposure to amikacin as a therapeutic advantage, especially in patients with renal impairment.
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Glucagon-like peptide 2 (GLP-2) decreases gastric and intestinal motility, reduces gastric secretions, promotes intestinal growth and improves post-resection structural and functional adaptation in short bowel syndrome (SBS). Teduglutide, an analogue of GLP-2, has a prolonged half-life and provides intestinotrophic effects with once-daily subcutaneous injection in patients with SBS. This monograph reviews the preclinical and clinical data that provide the scientific rationale for the use of teduglutide in this orphan condition. ⋯ Following its positive regulatory review and approval by the European Medicines Agency and the U. S. Food and Drug Administration in 2012, teduglutide has moved from the research setting to clinical practice, offering a new treatment paradigm for this burdensome and potentially life-threatening condition.
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Multiple myeloma (MM) is an incurable disease characterized by the proliferation of plasma cells. The survival in MM patients has improved significantly in the past decade due to the introduction of novel agents. ⋯ Although the development of novel agents has improved the outcomes of MM treatment, most of the patients will still relapse and become refractory to therapy due to development of drug resistance. A better understanding of the biological mechanisms of MM progression, including cellular and molecular events in the MM cells and in their bone marrow microenvironment, is warranted to provide new therapeutic targets and develop new drugs and therapeutic strategies to treat MM.
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Chronic obstructive pulmonary disease (COPD) is a worldwide problem causing prolonged and progressive morbidity as well as premature mortality. Pharmacologic treatment consists primarily in the relief of symptoms and preventing or minimizing the consequences of exacerbations. Central to the pharmacologic management of COPD is the use of bronchodilator therapy. ⋯ The availability of "ultra-long"-acting β-adrenoceptor agonists and long-acting antimuscarinic agents opens the way for combinations of these agents to be used in maintenance therapy. Such a combination offers the potential of enhanced efficacy due to additive effects and better compliance as the result of once-daily treatment. This article reviews the rationale for current bronchodilator therapy of COPD as well as the current status of a fixed-dose combined inhaler using two novel long-acting agents: glycopyrronium bromide and indacaterol maleate.
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After AIDS, tuberculosis (TB) is the leading killer worldwide due to a single infectious agent. Recently, drug-resistant strains of Mycobacterium tuberculosis elicited even more severe versions of TB. Bedaquiline inhibits mycobacterial ATP synthase. ⋯ At the end of 2012, the U. S. Food and Drug Administration approved bedaquiline (Sirturo®) as part of a combination therapy to treat adults with multidrug-resistant TB.