Alfuzosin for the treatment of storage symptoms suggestive of overactive bladder.

Expert Opin Pharmacother. 2012 Jun;13(8):1143-51

Authors: Cho KJ, Kim JC

Abstract
Introduction: Antimuscarinics are the mainstay of overactive bladder (OAB) pharmacotherapy although other agents, such as ?-adrenergic receptor antagonists, might also be effective. Alfuzosin has ?1-adrenoreceptor antagonist activity and is available worldwide for the treatment of lower urinary tract symptoms resulting from benign prostate hyperplasia. Alfuzosin may relieve storage symptoms suggestive of OAB in patients with or without bladder outlet obstruction (BOO). Areas covered: This paper reviews the available literature on the use of alfuzosin in the treatment of storage symptoms suggestive of OAB. Additionally, the role of ?-adrenoreceptor antagonists in the treatment of OAB is reviewed, based on pathophysiology. Expert opinion: Although alfuzosin is effective against storage symptoms, it does not improve them in all patients with OAB. It is likely that alternative types of therapy, such as antimuscrarinics, need to be co-administered to patients with residual storage symptoms after alfuzosin administration. Alfuzosin can decrease the risk of adverse events associated with antimuscarinics. The sequential use of alfuzosin and antimuscarinics appears to be an appropriate strategy for the treatment of storage symptoms suggestive of OAB related to BOO.

PMID: 22594844 [PubMed - in process]

Ceftaroline fosamil for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection.

Expert Opin Pharmacother. 2012 Jun;13(8):1177-86

Authors: Casapao AM, Steed ME, Levine DP, Rybak MJ

Abstract
Introduction: Bacterial resistance is increasing on a global basis, making treatment options more limited. The development of new agents to meet this threat is a matter of urgency. Ceftaroline fosamil , a member of an advanced cephalosporin class of antimicrobials, is currently approved by the US Food and Drug Administration for use in for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia. Ceftaroline displays activity against Gram-positive and Gram-negative bacteria, including both methicillin-susceptible and resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae (including penicillin- and ceftriaxone-resistant strains), respiratory pathogens (such as Moraxella catarrhalis and Haemophilus influenzae, including beta-lactamase-producing strains) and limited coverage against Enterobacteriaceae. Areas covered: Chemistry, mechanism of action, spectrum of activity, resistance, pharmacokinetics/pharmacodynamics, indications for use, safety and special populations are covered in this review. Expert opinion: Ceftaroline's unique activity against MRSA and penicillin- and ceftriaxone-resistant S. pneumoniae strains is due to its high affinity for penicillin binding protein (PBP)-2a and PBP-2x, respectively. In randomized, double-blinded, clinical trials, ceftaroline fosamil was found to be non-inferior to ceftriaxone for the treatment CABP and to vancomycin plus aztreonam for ABSSSI. Substantial differences between the cephalosporins exist. Ceftaroline has unique characteristics that may make it useful in specific clinical circumstances, especially against multi-drug-resistant Gram-positive organisms.

PMID: 22594846 [PubMed - in process]

Levofloxacin for the treatment of respiratory tract infections.

Expert Opin Pharmacother. 2012 Jun;13(8):1203-12

Authors: Torres A, Liapikou A

Abstract
Introduction: Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Levofloxacin , like other fluoquinolones, is a potent antibiotic, due to high levels of susceptibility among Gram-negative, Gram-positive (including penicillin-resistant strains of Streptococcus pneumonia) and atypical pathogens. Levofloxacin is recommended for the treatment of community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and in the management of acute exacerbations of chronic bronchitis (AECB). Levofloxacin demonstrates good safety, bioavailability and tissue penetration, thus maintaining adequate concentrations at the site of infection. High-dose (750 mg), short-course (5 days) therapy regimens may offer improved treatment, especially in HAP, due to higher drug concentrations, increased adherence and the potential to reduce the development of resistance. Areas covered: This article covers medical literature published in any language since 1990 until November 2011, on 'levofloxacin', identified using PubMed and MEDLINE. The search terms used were 'levofloxacin' and 'community acquired pneumonia', 'hospital pneumonia' or 'AECB'. Expert opinion: Levofloxacin is a valuable antimicrobial agent and an optimal treatment option for AECB, CAP (as a monotherapy) and HAP (as combination therapy at a high-dose regimen). Its improved bioavailability and safety profile makes the possibility of shorter hospital stays a reality.

PMID: 22594848 [PubMed - in process]

Targeting reperfusion injury in acute myocardial infarction: a review of reperfusion injury pharmacotherapy.

Expert Opin Pharmacother. 2012 Jun;13(8):1153-75

Authors: Sharma V, Bell RM, Yellon DM

Abstract
Introduction: Acute myocardial infarction (AMI) (secondary to lethal ischemia-reperfusion [IR]) contributes to much of the mortality and morbidity from ischemic heart disease. Currently, the treatment for AMI is early reperfusion; however, this itself contributes to the final myocardial infarct size, in the form of what has been termed 'lethal reperfusion injury'. Over the last few decades, the discovery of the phenomena of ischemic preconditioning and postconditioning, as well as remote preconditioning and remote postconditioning, along with significant advances in our understanding of the cardioprotective pathways underlying these phenomena, have provided the possibility of successful mechanical and pharmacological interventions against reperfusion injury. Areas covered: This review summarizes the evidence from clinical trials evaluating pharmacological agents as adjuncts to standard reperfusion therapy for ST-elevation AMI. Expert opinion: Reperfusion injury pharmacotherapy has moved from bench to bedside, with clinical evaluation and ongoing clinical trials providing us with valuable insights into the shortcomings of current research in establishing successful treatments for reducing reperfusion injury. There is a need to address some key issues that may be leading to lack of translation of cardioprotection seen in basic models to the clinical setting. These issues are discussed in the Expert opinion section.

PMID: 22594845 [PubMed - in process]

Combination therapy in type 2 diabetes mellitus: adding linagliptin to a stable regimen of metformin and a sulfonylurea.

Expert Opin Pharmacother. 2012 May 16;

Authors: Aronson R

Abstract
Linagliptin, the most recently approved drug of the dipeptidyl peptidase-4 (DPP-4) inhibitor class, is an oral agent used to improve glycemic control in type 2 diabetes mellitus (T2DM). By inhibiting the DPP-4 enzyme, these drugs slow the inactivation of the endogenous incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), in turn reducing blood glucose levels in a glucose-dependent manner. As well as significantly reducing glycosylated hemoglobin, the class has a good safety profile, with a low incidence of hypoglycemia, and is not associated with weight gain. From a practical point of view, they also have simple regimens, generally with once-daily oral administration, and can be used as monotherapy or in combination with other anti-diabetic drugs. Owens and colleagues have reported a 6-month study of linagliptin add-on therapy in patients who were receiving a stable regimen of metformin and a sulfonylurea, but needed additional glycemic control. Linagliptin was associated with significant improvement in glycemic control and was well-tolerated by patients, indicating that it provides a valuable option for a large number of patients with T2DM, especially for those who would prefer to add an oral therapy to a current regimen.

PMID: 22587735 [PubMed - as supplied by publisher]

Current treatment of nontuberculous mycobacteriosis: an update.

Expert Opin Pharmacother. 2012 May;13(7):967-86

Authors: Esteban J, García-Pedrazuela M, Muñoz-Egea MC, Alcaide F

Abstract
Introduction: Nontuberculous mycobacteria (NTM) are becoming increasingly important. A growing number of patients with underlying conditions that make them prone to diseases caused by NTM. These diseases include the appearance of new syndromes, such as mesotherapy and other cosmetic-related infections, or diseases that affect patients who are being treated with tumor necrosis factor. Areas covered: A literature search has been performed for each mycobacterium species. An introduction to the different aspects of the species and the diseases is provided, along with a review of the current therapeutic options; special emphasis is put on new research and discoveries. Expert opinion: Recognition of the current role of NTM isolates remains the key step in the management of NTM infections. After recognition, treatment must be guided by attending to the isolated species, the specific syndromes, clinical experience and - for some species - the results of in-vitro susceptibility tests. Surgical therapy is also important for some species (Mycobacterium ulcerans, Mycobacterium scrofulaceum) and for localized infections. The treatment of uncommon species is not yet well defined and recent research on resistance mechanisms has described their importance. The role of biofilms is currently of special concern for various specific infections.

PMID: 22519767 [PubMed - in process]

Dabigatran or warfarin for the prevention of stroke in atrial fibrillation? A closer look at the RE-LY trial.

Expert Opin Pharmacother. 2012 Mar 22;

Authors: Dinicolantonio JJ

Abstract
Introduction: In the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) trial, dabigatran 150 mg was shown to be superior to warfarin for the prevention of stroke or systemic embolism. However, there are some concerns with the RE-LY trial, such as its open-label design, potential unblinding of "blinded" adjudicators, the use of concomitant warfarin-aspirin (ASA), the disparity between baseline use of nonselective NSAIDs; the high unequal rate of drop-outs; unaccounted drop-ins; high rates of major bleeds in warfarin-treated patients, despite being a low risk population; and rates of major bleeds that do not match historic warfarin trials. Furthermore, although dabigatran offers potential advantages versus warfarin, there are disadvantages that must be taken into consideration before a patient is switched from the latter to the former. This review will summarize the flaws of the RE-LY trial as well as the clinically important advantages and disadvantages of dabigatran and warfarin. Areas covered: This review examines the differences between dabigatran and warfarin in terms of side effects, drug-drug interactions, drug-food interactions, and potential reasons for using one anticoagulant rather than the other. The main focus of this review is a discussion of the design, procedures and results of the RE-LY trial. Expert opinion: There seem to be major flaws with the RE-LY trial. A double-blinded trial should be performed testing dabigatran against warfarin to verify the results of the RE-LY trial.

PMID: 22435606 [PubMed - as supplied by publisher]

Levosalbutamol for chronic obstructive pulmonary disease: a treatment evaluation.

Expert Opin Pharmacother. 2012 Feb 25;

Authors: Patel M, Thomson NC

Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder associated with considerable morbidity and mortality. ?2-adrenoceptor agonists (?2-agonists) act by stimulating the ?2-adrenoceptor present on smooth muscle and other cells in the airways, resulting in bronchodilatation. ?2-agonists play a central role in the treatment of breathlessness in patients with COPD. Salbutamol is a chiral drug with (R)- and (S)- isomers. Almost all ?2-agonists that are currently used are racemic mixtures of (R)- and (S)-salbutamol. Areas covered: (R)-salbutamol alone (Xenopex®, generically known as levosalbutamol) is now indicated for the treatment or prevention of bronchospasm with reversible obstructive airway disease. This evaluation demonstrates that (R)-salbutamol provides a beneficial ?2-agonist effect at a cellular level and in experimental models of airways disease. Furthermore, we demonstrate that (S)-salbutamol opposes the desirable effects of (R)-salbutamol and can actually cause features of asthma and COPD in vitro and in experimental asthma. Expert opinion: Despite this strong body of preclinical experimental evidence, (R)-salbutamol has not shown consistent superiority over (S)- or racemic salbutamol in the treatment of patients with COPD.

PMID: 22364295 [PubMed - as supplied by publisher]

Management of antithrombotic therapy for acute coronary syndromes and atrial fibrillation in patients with hemophilia.

Expert Opin Pharmacother. 2012 Feb 15;

Authors: Mannucci PM

Abstract
Introduction: Patients with hemophilia now have a life expectancy very close to that of the unaffected male population and, hence, are at risk of developing the classic age-related morbidities, i.e., cardiovascular diseases. The peculiarity of the management of these diseases in hemophilia is that antithrombotic drugs impinge on the already compromised hemostasis of these lifelong bleeders. Areas covered: This opinion article outlines the strategies we have developed, based on our clinical experience, for the antithrombotic treatment of two common cardiovascular diseases - acute coronary syndromes and chronic atrial fibrillation - in patients with hemophilia A and B. Expert opinion: In the absence of specific evidence-based guidelines for patients with coagulation defects, antithrombotic treatment is currently based on expertise and adaptation of the guidelines developed for non-hemophilic patients. Replacement therapy should be tailored with the deficient coagulation factor so as to control the increased risk of bleeding inherent in the use of antiplatelet and anticoagulant drugs.

PMID: 22332913 [PubMed - as supplied by publisher]

Antiviral treatment of cytomegalovirus infection: an update.

Expert Opin Pharmacother. 2012 Feb 2;

Authors: Härter G, Michel D

Abstract
This editorial summarizes recent developments in the management of ganciclovir-resistant human cytomegalovirus (HCMV) infections. All current drugs available for systemic treatment, including ganciclovir (GCV), valganciclovir, foscarnet and cidofovir, target the viral polymerase. However, all such compounds are hampered by dose-related toxicities and the emergence of resistance. Different approaches (e.g., PCR-based direct sequencing, pyrosequencing, mass spectrometry-based comparative sequencing) allow the fast detection of resistant HCMV and are well suited to therapy monitoring. However, more studies are required on the dynamic of mixed HCMV populations under drug pressure. Alternate antiviral compounds with new mechanisms of action, such as artesunate, leflunomid, letermovir and maribavir, are now being investigated in clinical studies. An advantage of some of the new substances is lesser toxicity issues, which might lead to new prophylactic and treatment strategies.

PMID: 22299626 [PubMed - as supplied by publisher]

Tiotropium: what came after the UPLIFT study.

Expert Opin Pharmacother. 2012 Jan 28;

Authors: Santus P, Di Marco F, Radovanovic D, Centanni S

Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive bronchial obstruction, and bronchodilators represent the maintenance therapeutic choice. Tiotropium is an anticholinergic drug that is proved to be safe, efficient and simple to handle; Respimat® technology was recently introduced as a new device for tiotropium administration. Areas covered: This paper reviews clinical trials and meta-analyses, with tiotropium efficacy as a primary end point, found in MedLine, the Cochrane trials database and Embase. Only the literature published after the UPLIFT study has been considered. Expert opinion: Data published after the UPLIFT study confirms the efficacy of tiotropium as maintenance COPD therapy and its capacity to reduce airflow obstruction, as well as lung hyperinflation. Nevertheless, there is a certain inhomogeneity in the definition and evaluation of COPD exacerbations, in lung functional parameters and quality-of-life assessment, and there has not always been a proper comparison between tiotropium and other long-acting bronchodilators. Respimat is comparable in efficacy to the HandiHaler®, using bioequivalent doses of tiotropium.

PMID: 22283503 [PubMed - as supplied by publisher]

Tapentadol for pain: a treatment evaluation.

Expert Opin Pharmacother. 2011 Dec 23;

Authors: Hartrick CT, Rodríguez Hernandez JR

Abstract
Tapentadol is a newly approved novel analgesic drug with a dual mode of action: a mu-opioid agonist and an inhibitor of norepinephrine reuptake (MOR-NRI). Preclinical evidence supports a synergistic interaction between these two effects. It is the first opioid agonist to exhibit predominant norepinephrine reuptake inhibition with minimal serotonin effects. It is FDA approved for use in the US for moderate to severe pain in adults, available in the immediate release form for acute pain and as an extended-release formulation for chronic pain when continuous analgesia is required. Tapentadol has demonstrated reduced treatment-emergent opioid-related gastrointestinal adverse effects compared with pure opioid agonists. The synergistic mu-opioid and alpha(2)-adrenergic effects suggest the potential for particular utility in neuropathic pain states or other pain states associated with hyperalgesia.

PMID: 22192161 [PubMed - as supplied by publisher]

The use of insulin in elderly patients with type 2 diabetes mellitus.

Expert Opin Pharmacother. 2011 Nov 16;

Authors: Mannucci E, Cremasco F, Romoli E, Rossi A

Abstract
Introduction: Older patients with diabetes sometimes present comorbidities that increase the risk of other common geriatric syndromes. In such patients, treatment with insulin is usually started when full doses of oral hypoglycemic agents are no longer adequate to achieve acceptable glycemic control. Areas covered: This article reviews the available literature on the use of insulin in elderly patients with type 2 diabetes. The aims are to gain information on: the benefits and risks of initiating insulin treatment, the efficacy and safety of different types of insulin and the most appropriate initial dosing and titration regimens. Thirteen published trials have evaluated the effects of different insulin regimens in the management of elderly subjects with type 2 diabetes but, given that older people are generally excluded in clinical studies with insulin, only three published reports on subgroup analyses are limited to elderly patients. Expert opinion: The available literature shows that the addition of insulin to current oral treatments is generally safe and effective in improving metabolic control, with a low risk for hypoglycemia. Further research is needed to better understand the most appropriate insulin regimens necessary to achieve glycemic goals while appropriately addressing the risk of hypoglycemia.

PMID: 22087577 [PubMed - as supplied by publisher]

Medical management of neurocysticercosis.

Expert Opin Pharmacother. 2011 Nov 15;

Authors: Takayanagui OM, Odashima NS, Bonato PS, Lima JE, Lanchote VL

Abstract
Introduction: Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). Areas covered: All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. Expert opinion: Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies ? especially randomized controlled trials in long-term clinical evolution ? are required to clarify the controversy over the validity of parasitic therapy in patients with NCC.

PMID: 22082143 [PubMed - as supplied by publisher]

Mineralocorticoid receptor antagonists for heart failure.

Expert Opin Pharmacother. 2011 Nov 14;

Authors: Richards AM

Abstract
Introduction: Although mineralocorticoid receptor (MR) antagonists are indicated in systolic heart failure, they are underprescribed in patients with appropriate indications for their prescription and often used in those in whom the evidence for probable benefit is scant. The rate of adverse events in practice has exceeded that foreshadowed by randomized controlled trials (RCTs). With the recent publication of the landmark therapeutic trial (EMPHASIS), it is timely to review the appropriate use of these agents in heart failure. Areas covered: This review addresses the pathophysiological importance of MR activation in heart failure and summarizes pivotal RCTs of MR antagonists in heart failure. Expert opinion: MR antagonism reduces mortality and morbidity in heart failure with reduced systolic function in severe chronic disease, in heart failure complicating myocardial infarction and also in those with impaired systolic function (but only mild symptoms). Evidence for benefits in a significant proportion of ?real-life? patients with heart failure, including those with preserved left ventricular ejection fraction, is lacking. MR antagonism is an important part of the pharmaceutical armamentarium in managing heart failure but must be prescribed with careful case selection, taking note of the evidence of where risks are acceptable and benefits are likely.

PMID: 22082128 [PubMed - as supplied by publisher]