SGLT-2 inhibitors and their potential in the treatment of diabetes.

Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids.

Management of hypertension with fixed-dose triple-combination treatments.

The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed that half the patients with hypertension have uncontrolled blood pressure (BP), with underlying factors including therapeutic inertia and poor patient adherence. Many patients will require three antihypertensive agents to achieve BP goals, and current guidelines recommend combining drugs with complementary mechanisms of action.

The evolving landscape of RAAS inhibition: from ACE inhibitors to ARBs, to DRIs and beyond.

Chronic renin-angiotensin-aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to cardiovascular (CV) disease and renal dysfunction. The vascular effects of sustained RAAS activation are associated with hemodynamic imbalances, as well as inflammatory stimulation and prothrombotic processes that lead to fibrosis, endothelial dysfunction and cellular remodeling. RAAS inhibition therapies, which include the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and more recently, direct renin inhibitors, have been used in clinical practice for more than 30 years.

Dapagliflozin: a novel sodium-glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.

The prevalence of diabetes mellitus has grown to staggering numbers, and its incidence is expected to rise in the next 2 decades. The need for novel approaches to treat hyperglycemia cannot be ignored. Current agents have been shown to modestly improve glycemia and in some cases prevent complications of diabetes, but they become less effective over time and are often accompanied by undesirable adverse effects.

Carvedilol reduces aortic wave reflection and improves left ventricular/vascular coupling: a comparison with atenolol (CENTRAL Study).

Blood pressure (BP) characteristics, such as central aortic pressure and arterial stiffness, independently predict cardiovascular events. The effects of pharmacologically dissimilar β-blockers on these properties have not been fully elucidated. Patients with essential hypertension and without significant concomitant cardiovascular disease were randomly assigned to controlled-release carvedilol, force-titrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg (n=19); each was given once daily for 4 weeks.

Nonpharmacological interventions for the treatment of rheumatoid arthritis: a focus on mind-body medicine.

Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects approximately 1.3 million Americans. It is characterized by inflammation of the joints, most often affecting the hands, hips, and knees.

Aliskiren and valsartan combination therapy for the management of hypertension.

Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA), a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function.

Improving blood pressure control rates by optimizing combination antihypertensive therapy.

Importance Of The Field: Hypertension is the most common preventable cause of cardiovascular morbidity and mortality. Despite the availability of a multitude of antihypertensive drugs, blood pressure (BP) control rates remain poor in the majority of patients with hypertension due to both patient- and clinician-related factors. The purpose of this review is to describe how healthcare professionals can best utilize combination therapy to optimize patient antihypertensive treatment and achieve BP goals.

How to obtain appropriate type 2 diabetes control in the first 180 days of treatment initiation.

Good control of diabetes provides meaningful microvascular risk reduction; yet, patients with type 2 diabetes mellitus commonly languish at unsatisfactory levels of glycated hemoglobin (HbA1c) for protracted periods. A variety of factors contribute to this clinical inertia, as clinicians tend to be too conservative in their treatment of patients who are not achieving glycemic control. Available clinical data suggest the near-maximal blood glucose reduction achievable with use of most antidiabetic agents typically occurs within several weeks of treatment initiation.

Efficacy and safety of ticagrelor: a reversible P2Y12 receptor antagonist.

Objective: To summarize the pharmacokinetic and pharmacodynamic properties of ticagrelor, a selective P2Y12 receptor antagonist, and evaluate its role in the treatment of patients with acute coronary syndromes (ACS).

Data Sources: A literature search was conducted in MEDLINE (1966-November 2009), International Pharmaceutical Abstracts (1970-November 2009), and EMBASE (1990-November 2009) using the MeSH terms and key words AZD6140, ticagrelor, P2Y12 receptor antagonist, cardiovascular disease, ACS, atherothrombosis, and platelets.

Study Selection And Data Extraction: Selected studies evaluated the pharmacology, pharmacokinetics, pharmacodynamics, safety, and efficacy of ticagrelor for the treatment of ACS.

Recent changes in the landscape of combination RAS blockade.

The renin-angiotensin system (RAS) is a prime target for cardiovascular drug therapy. Inhibition of the RAS lowers blood pressure and confers protection against cardiovascular and renal events. These latter benefits cannot be entirely attributed to blood pressure lowering.

Optimizing management of hypertension with combination therapy: considerations for the nurse practitioner.

Hypertension is an important contributor to the risk of cardiovascular disease and death, yet success in achieving blood pressure (BP) control has been limited. Most patients will require 2 or more medications to control their BP. Nurse practitioners play a vital role in treating patients with hypertension and can help overcome barriers to reaching BP goals.

Managing peripheral edema in patients with arterial hypertension.

Calcium channel blockers (CCBs) play a vital role in the management of hypertension. Peripheral edema is the most common side effect reported with CCB monotherapy, especially with high-dose dihydropyridine CCBs. CCB-related peripheral edema is a dose-limiting effect that is usually medically benign but can compromise patient adherence.

Endothelin receptor antagonists as antihypertensives: the next frontier.

The endothelin system is a pivotal player along the continuum of cardiovascular disease. There is convincing evidence that the system not only exerts a potent pressor effect but also promotes end-organ damage independent from blood pressure changes. The role of endothelin receptor antagonists (ERAs) in the treatment of hypertension is rapidly evolving.

Actions of selected cardiovascular hormones on arterial stiffness and wave reflections.

The large conduit arteries of the thorax and abdomen are elastic while those in the arms and legs are muscular. Alterations in wall properties of elastic arteries occur over time and are usually permanent in nature; acute changes can, however, occur is response to a change in transmural pressure. Chronic alterations in properties of muscular arteries are minimal but changes (e.

Efficacy and safety of darusentan: a novel endothelin receptor antagonist.

Objective: To summarize the role of the endothelin system (ETS) in cardiovascular disease (CVD) and evaluate the potential usefulness of darusentan, a selective endothelin type A (ET(A)) receptor antagonist, in the treatment of hypertension and chronic heart failure (CHF).

Data Sources: A literature search was conducted in MEDLINE (1966-February 2008), International Pharmaceutical Abstracts (1970-February 2008), and EMBASE (1990-February 2008) using the search terms endothelin, darusentan, LU 135252, hypertension, and heart failure.

Study Selection And Data Extraction: Studies evaluating the role of the ETS in CVD and the pharmacology, pharmacokinetics, safety, and efficacy of darusentan for the treatment of hypertension and CHF were included.

Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff.

The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension.

Dihydropyridine calcium channel antagonists in the management of hypertension.

Dihydropyridine calcium channel antagonists have been maligned in recent years because of concerns regarding their cardiovascular and overall safety profile. Specifically, it was widely publicised in the mid-1990s that these agents might increase the risk of myocardial infarction, gastrointestinal bleeding and cancer. Data linking these agents with increased cardiovascular risk were based on nonrandomised studies and implicated short-acting, immediate-release agents.

Drug evaluation: PSN-9301, a short-acting inhibitor of dipeptidyl peptidase IV.

(OSI) Prosidion is developing PSN-9301, a rationally designed dipeptidyl peptidase IV inhibitor acquired from Probiodrug AG, as a potential oral treatment for type 2 diabetes. Phase II clinical trials of PSN-9301 are underway.

Newer agents for the management of overactive bladder.

The anticholinergics tolterodine and oxybutynin are well established in the management of overactive bladder. However, their activity at muscarinic receptors distant from the target site (i.e.

Optimal pharmacological therapy for community-acquired pneumonia: the role of dual antibacterial therapy.

The optimal pharmacological therapy of community-acquired pneumonia (CAP) is one of the most ardently debated issues in medicine. Presently, most guidelines recommend either a fluoroquinolone alone or dual therapy with a third-generation cephalosporin plus a macrolide in patients hospitalised with CAP, but few provide clinicians with specific considerations for selecting from these agents. Despite a similar spectrum of activity and favourable resistance patterns (for fluoroquinolones and third-generation cephalosporins) against CAP pathogens, there is emerging evidence that dual therapy may be superior to monotherapy in certain populations.

Can the renin-angiotensin system protect against stroke? A focus on angiotensin II receptor blockers.

From a patient's perspective, stroke is the most devastating form of cardiovascular disease, representing the number one cause of permanent disability in the United States. Treatment of hypertension significantly reduces the risk of stroke; however, it is unclear whether all antihypertensive agents are equivalent in this regard. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the risk of cardiovascular events, including stroke.