Oct 112014
 

Phosphodiesterase Inhibitors for Chronic Obstructive Pulmonary Disease: What Does the Future Hold?

Drugs. 2014 Oct 10;

Authors: Matera MG, Rogliani P, Calzetta L, Cazzola M

Abstract
Phosphodiesterase-4 (PDE4) inhibitors have broad anti-inflammatory activity, inhibiting the airway inflammation associated with chronic obstructive pulmonary disease (COPD), especially by reducing airway neutrophils that are key cells in COPD. A careful evaluation of the results of several meta-analyses allows us to consider the use of PDE4 inhibitors as very important in those patients with COPD who are particularly susceptible to exacerbations, the so-called 'frequent exacerbators'. Consequently, PDE4 inhibitors should be used earlier and more frequently than is the case today, but they are prescribed sporadically because of side effects. Several strategies are conceivable to avoid side effects, but, unfortunately, many of these approaches are yet to be successfully translated into clinical effectiveness after several decades of research. A novel alternative approach is to administer multiple drugs simultaneously or drugs capable of two distinct primary pharmacological actions based on distinct pharmacophores (bifunctional drugs) in order to produce additive or synergistic effects and, consequently, to dispense these drugs at lower doses, inducing fewer side effects. The fact that we have realized that there is a need to target simultaneously more PDEs unquestionably represents an advance in the possible use of PDE inhibitors. Actually, the possibility that multivalent (multifunctional) ligands, which feature two or more pharmacophores, may deliver superior efficacy is an approach that is being explored. Recognizing the role of specific targeted therapy aimed at subcellular domains has changed our understanding of the use of PDE inhibitors, and offers an opportunity to improve both the therapeutic tolerability and efficacy of these drugs.

PMID: 25300411 [PubMed - as supplied by publisher]

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Oct 112014
 

New Oral Anticoagulants for the Treatment of Venous Thromboembolism: Understanding Differences and Similarities.

Drugs. 2014 Oct 10;

Authors: Dobesh PP, Fanikos J

Abstract
Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These new oral agents have been evaluated for safety and efficacy in large, randomized clinical trials in the treatment and secondary prevention of VTE with results that are comparable to conventional therapy. Dabigatran, rivaroxaban, apixaban, and edoxaban are important new treatment options for patients with VTE. In this review, we compare these new agents and their associated clinical trials in VTE treatment.

PMID: 25300410 [PubMed - as supplied by publisher]

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Oct 032014
 
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Empagliflozin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus.

Drugs. 2014 Oct 2;

Authors: Scott LJ

Abstract
Oral empagliflozin (Jardiance(®)), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus. By inhibiting reabsorption of glucose from the proximal tubules in the kidney via inhibition of SGLT2, empagliflozin provides a novel insulin-independent mechanism of lowering blood glucose. In several phase III trials (≤104 weeks' duration; typically 24 weeks' duration) and extension studies (typically ≥76 weeks' treatment), empagliflozin monotherapy or add-on therapy to other antihyperglycaemics, including insulin, improved glycaemic control and reduced bodyweight and systolic blood pressure in adult patients with type 2 diabetes. In a large phase III trial, as add-on therapy to metformin, empagliflozin was shown to be noninferior to glimepiride at 52 and 104 weeks and superior to glimepiride at 104 weeks, in terms of reductions in glycated haemoglobin level (primary endpoint). Empagliflozin was well tolerated by participants in these clinical trials, with most adverse events being mild or moderate in intensity. Empagliflozin treatment appeared to have no intrinsic risk of hypoglycaemia, although hypoglycaemia occurred more frequently when empagliflozin was coadministered with insulin and/or a sulfonylurea. With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes. This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.

PMID: 25274537 [PubMed - as supplied by publisher]

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Sep 232014
 
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Antiepileptic Drugs for the Treatment of Agitation and Aggression in Dementia: Do They Have a Place in Therapy?

Drugs. 2014 Sep 20;

Authors: Gallagher D, Herrmann N

Abstract
Antiepileptic drugs (AEDs) are a class of medications that have received considerable attention as possible treatments for agitation and aggression in patients with dementia. This attention has been driven in equal measure by promising findings from limited trial and observational data and the desire to find treatments with improved tolerability. Their use, to date, has been largely confined to circumstances where first-line treatments have proven inadequate or are poorly tolerated. In recent years there has been some growth in the evidence base, and we can now make more informed recommendations regarding a number of older AEDs. Carbamazepine continues to have the best evidence to support its use, although the evidence base remains relatively small and concerns regarding tolerability limit its use. There is now more consistent evidence that valproate preparations should not be used for agitation and aggression in dementia. Despite a lack of high-quality data, some results have been reported for several newer medications, including levetiracetam, oxcarbazepine, gabapentin, topiramate and lamotrigine, and a number of these warrant further investigation. Recent findings and implications for clinical practice are discussed.

PMID: 25239267 [PubMed - as supplied by publisher]

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Sep 232014
 
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Oritavancin: First Global Approval.

Drugs. 2014 Sep 20;

Authors: Markham A

Abstract
Oritavancin (Orbactiv(®)) is a lipoglycopeptide antibacterial drug with activity against Gram-positive bacteria developed by The Medicines Company as a single-dose treatment for acute bacterial skin and skin structure infections (ABSSSI). The drug received its first global approval for this indication in the US in August 2014, and is under regulatory review in the EU. This article summarises the milestones in the development of oritavancin leading to this first approval for the treatment of ABSSSIs caused by Gram-positive bacteria.

PMID: 25239268 [PubMed - as supplied by publisher]

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Sep 112014
 
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Systemic Glucocorticoid Therapy: a Review of its Metabolic and Cardiovascular Adverse Events.

Drugs. 2014 Sep 10;

Authors: Fardet L, Fève B

Abstract
The prevalence of use of long-term systemic glucocorticoid therapy in the general adult population is 1 %. This figure increases to up to 3 % in elderly women. Metabolic (i.e. diabetes mellitus, dyslipidemia, weight gain, lipodystrophy) and cardiovascular (i.e. hypertension, cardiovascular events) adverse events are commonly observed in these patients and can be life threatening. Paradoxically, there is very few data on some of these adverse events and many of the available studies remain inconclusive. Incidence of and risk factors for dyslipidemia, weight gain and lipodystrophy are poorly defined. The optimal treatment plan for patients diagnosed with glucocorticoid-induced diabetes or hypertension is undetermined. Finally, there is no medical consensus on the best strategies for the prevention and detection of these complications. However, certain of these questions can be answered by looking at available data on patients with endogenous hypercortisolism (i.e. Cushing's syndrome). This article reviews the pathophysiology, incidence, risk factors, screening, and treatment of glucocorticoid-induced weight gain, lipodystrophy, diabetes, dyslipidemia, hypertension, and cardiovascular events. It also focuses on the possible prevention of these adverse events by targeting the glucocorticoid receptor using selective glucocorticoid receptor modulators.

PMID: 25204470 [PubMed - as supplied by publisher]

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