Management of essential hypertension

Hypertension, in spite of a very high prevalence, remains undertreated. This is not due to a lack of effective therapeutic modalities. Non-pharmacological treatments can be effective in many patients. If those treatments fail to reduce blood pressure sufficiently, the physician can choose between numerous classes of antihypertensive agents. However, interpatient variability in response to these agents is high, and use of multiple agents is frequently necessary. Thus, no single class has proven to be superior for the majority of patients. This article will review the different non-pharmacological and pharmacological methods available to treat hypertension, as well as the guidelines that are available to aid in proper selection of a treatment regimen.     

Neuropathic pain: strategies in drug discovery and treatment

Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. In contrast to acute nociceptive pain, the cascade of events that arise following peripheral nerve injury leads to a maintained abnormality in the sensory system, resulting in an abnormal pain phenomenon that can be grossly debilitating. At present, there are very few effective and well-tolerated therapies for neuropathic pain. The development of animal models and constant progress in the understanding of the basic pathophysiology of neuropathic pain has led to multifarious drug targets and treatment options. The most effective agents are use-dependent inhibitors of Na⁺ channels, namely phenytoin, lamotrigine and carbamazepine. Owing to an effect of increase in the serotonin and various other biogenic amine levels on the pain modulating system, various classes of antidepressants including selective serotonin re-uptake inhibitors and selective noradrenaline re-uptake inhibitors are being used clinically. Modulation of Ca²⁺ channels is another useful approach for the treatment of neuropathic pain. In particular, the modulation of N-type Ca²⁺ channels, which are expressed primarily in central and peripheral nervous tissues, has been the subject of greatest interest. In view of the above, this review discusses the various strategies and approaches to novel drug discovery and pharmacotherapy of neuropathic pain syndromes.     

Alfuzosin for the treatment of storage symptoms suggestive of overactive bladder

Introduction: Antimuscarinics are the mainstay of overactive bladder (OAB) pharmacotherapy although other agents, such as α-adrenergic receptor antagonists, might also be effective. Alfuzosin has α1-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 α-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.     

Novel approaches to the treatment of acute renal failure

Acute renal failure (ARF) occurs frequently in hospitalised patients and is associated with significant morbidity and mortality. Many therapeutic strategies have been undertaken both to prevent acute renal injury and, once ARF occurs, to improve renal function and reduce mortality. Among the available pharmacological options, no specific therapy has been shown to alter the course of ARF. This article reviews the efficacy of several strategies in experimental renal disease and raises the possibility that similar interventions might be available to the clinician in the near future for the prevention and management of ARF. The prospect of these novel strategies together with the ever-increasing understanding of the complex pathophysiology of ARF, offers the promise of effective and more physiological therapeutic interventions in this new millennium.     

Use of atypical antipsychotic agents in bipolar and schizoaffective disorders: review of the empirical literature.

Atypical antipsychotic agents seem to be effective treatments for bipolar disorder, especially as adjunctive treatments. They may be a safer and more effective alternative to the common practice of maintenance adjunctive treatment with traditional antipsychotic agents in patients with bipolar disorder. However, currently available research studies are limited methodologically mainly to open-label, uncontrolled designs. Further research is required before the definitive efficacy of these agents in bipolar disorder is established. If randomized or double-blind data support the open-label data reviewed here, atypical antipsychotic agents may possess an important role in the adjunctive treatment of bipolar disorder.     

Advances in orally administered pharmacotherapy for the treatment of migraine

Introduction: Migraine is a common and highly disabling neurological disorder whose acute treatment remains problematic and unsatisfactory in a high percentage of cases. Consequently, there remains a need for new symptomatic therapies that can be easily handled by patients (i.e. by oral administration).

Area covered: This review reports on compounds currently under development for the oral treatment of acute migraine attacks, focusing on Calcitonin-Gene-Related-Peptide receptor antagonists, specifically ubrogepant and rimegepant. This article is based on literature obtained from PubMed and publicly available clinical trial data.

Expert opinion: Both reviewed compounds meet the need for rapid and effective pain control, combined with the control of associated bothersome symptoms while also lacking significant adverse events and safety concerns. Though further studies should assess the profile of these compounds comparatively with existing and available treatments (namely triptans), the currently available data points to these new therapies as being very promising new symptomatic oral treatments of migraines.     

Novel approaches to the treatment of acute renal failure

Acute renal failure (ARF) occurs frequently in hospitalised patients and is associated with significant morbidity and mortality. Many therapeutic strategies have been undertaken both to prevent acute renal injury and, once ARF occurs, to improve renal function and reduce mortality. Among the available pharmacological options, no specific therapy has been shown to alter the course of ARF. This article reviews the efficacy of several strategies in experimental renal disease and raises the possibility that similar interventions might be available to the clinician in the near future for the prevention and management of ARF. The prospect of these novel strategies, together with the ever-increasing understanding of the complex pathophysiology of ARF, offers the promise of effective and more physiological therapeutic interventions in this new millennium.     

Outcomes associated with the use of biologic agents in moderate to severe psoriasis

An estimated 2.1% of Americans have psoriasis and approximately 30% of them have moderate to severe psoriasis. Although the disease is not associated with mortality, it has a significant impact on health-related quality of life among patients. Several therapies are available for psoriasis including topical agents, phototherapy, and systemic medications. Recently, effective yet expensive biologic agents have been added as treatments for moderate to severe psoriasis. Biologics are recommended in patients for whom all other available treatment options have failed. This extensive review provides important information on the clinical and patient-related outcomes associated with the biologic agents used in psoriasis.     

Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines

Introduction: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD.

Areas covered: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged ≤ 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.

Expert opinion: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.     

临床应用二氢吡啶类钙通道阻滞剂的循证医学评价

目的：评价二氢吡啶类钙通道阻滞剂（DHP—CCB）的临床应用进展,及其有效性和安全性。方法：搜集DHP—CCB临床应用相关的系统评价及大规模临床对照研究,对DHP—CCB和安慰剂或者其它药物进行比较,评价其有效性和安全性。结果：共检索到3项大型临床研究和20项系统评价,对DHP—CCB应用于高血压、心绞痛、蛛网膜下腔出血、抑制分娩等症状的有效性和安全性进行评价。结论：DHP—CCB在控制收缩压和舒张压上和其它药物效果相同,与其它降压药合用,效果和安全性更好。在老年单纯收缩期高血压患者,应用DHP—CCB明显降低肾功能不全和痴呆。DHP—CCB与β-受体阻滞剂合用于冠心病患者中,效果和安全性更好。DHP—CCB能够改善蛛网膜下腔出血预后。在抑制分娩中,DHP—CCB较其它抑制分娩药更有效,安全性更好。DHP—CCB应用于缺血性卒中的安全性和有效性尚待进一步的临床数据证实。     

Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI

Individuals with social phobia (SP) fear and avoid a wide variety of social and performance situations in which they are exposed to unfamiliar persons or to possible scrutiny by others. The lifetime prevalence of SP is estimated to be as high as 13%. It is frequently co-morbid with and usually precedes the onset of other psychiatric illnesses and is associated with significant occupational and social impairment, including academic and vocational underachievement. Fortunately, there are effective treatments for this common and debilitating condition. There is currently considerable evidence for the efficacy of pharmacotherapy and especially the monoamine oxidase inhibitors (MAOIs) and selective serotonin re-uptake inhibitors (SSRIs) in the treatment of this disorder. However, SSRIs are generally preferred as the first-line treatment of choice due to the advantages of SSRIs over MAOIs in terms of safety and tolerability. Despite encouraging results, current treatments most often produce partial symptomatic improvement, rather than high end-state functioning. While current first line treatments for social phobia target the serotonergic system, it is important to remember that different social fears are likely to have different developmental roots and may be based on quite different neurobiological systems. In this article we provide a review of current pharmacotherapeutic options for SP, current knowledge of the neurobiology of SP, and a review of new and promising directions in pharmacological research. It is increasingly clear that serotonin (5-HT) is unlikely to be the whole story in SP and that other brain chemical systems, especially the dopaminergic, noradrenaline-corticotropin releasing hormone and γ-aminobutyric acid (GABA) dependent systems, most probably have an important role to play in a substantial percentage of cases. A number of new and novel agents, including the substance P antagonists, GABA agonists and CRF antagonists show considerable promise in the treatment of SP. However, in order to enhance the understanding of the neurobiology and treatment response of SP, we need to develop more sophisticated theory-driven typologies of SP.     

Emerging drug therapies for benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is the nonmalignant enlargement of the prostate gland caused by increases in number of both epithelial and stromal cells. Clinically, BPH leads to voiding dysfunction, which is most often referred to as lower urinary tract symptoms (LUTS). Historically, the only treatments for LUTS due to BPH were watchful waiting or surgery (transurethral or open prostatectomy). However, over the last 20 years medical therapy has taken a prominent role in the management of BPH. Current medical treatments for BPH include α-adrenergic receptor antagonists, inhibitors of the 5-α reductase enzyme and various phytotherapies. These agents are generally effective and safe; however, many patients are unable to tolerate the side effects or are refractory to medical management and require surgery. In light of this, many potential new therapies for the treatment of BPH are under development. Some represent a variation of current treatments, whereas others target novel molecular pathways within the prostate. The aim of this review is to examine current pharmacotherapies as well as to highlight emerging drugs that may improve our treatment of patients with LUTS secondary to BPH.     

Calcium-channel modulators for cardiovascular disease

The advent of the anti-TNF agent infliximab has dramatically changed our concept of treating refractory inflammatory bowel disease, particularly Crohn’s disease. Although infliximab has proven to induce clinical response and remission with rapid onset of mucosal healing, to spare steroids, to improve perianal disease and to increase quality of life, there is an ongoing debate about optimizing infliximab therapy and a clear unmet medical need for patients losing their response to this agent. Novel anti-TNF agents, mostly more humanized monoclonal antibodies, with subcutaneous administration, have shown efficacy and are in advanced stages of clinical development. Compounds targeted at alternative pathways in the immune cascade are not expected to enter the market soon. Promising novel therapeutic classes include the anti-IL-12/23 and anti-IFN-γ agents and the selective adhesion molecule inhibitors. Most of the biologic therapies, including anti-TNF agents, are aimed at crucial pathways in the immune system on the crossroads between immune pathology and host defense. Therefore, long-term benefit to risk profiles need to be established for all novel drugs.     

Recent advances in feeding suppressing agents: potential therapeutic strategy for the treatment of obesity

Obesity is an increasingly prevalent health problem for which no ideal treatments are available, especially for long-term maintenance of body loss. The only approved drugs are centrally acting appetite suppressants that modulate monoamine neurotransmitters in the brain. Since the discovery of leptin, and the fact it modulates neuropeptide systems in the CNS, attention has shifted from amines to peptides. Many researchers have focused on these neuropeptide systems in the CNS and their involvement in energy balance. With an effort to identify molecules involved in feeding behaviour and energy expenditure in the brain, especially in the hypothalamic nuclei, a series of novel potential targets for the development of anti-obesity agents, as well as potential drug candidates, are being given attention. Many pharmaceutical companies have large programmes directed at the development of new modulators of neuropeptide receptors, antagonists of appetite enhancing peptides and agonists of appetite suppressing peptides, including neuropeptide Y receptors and melanocortin receptors. This review covers recent targets for drug discovery of anti-obesity agents and patents focusing on the receptors.     

How to use calcium antagonists in hypertension: putting the JNC-VI guidelines into practice. Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure.

The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.     

Angiotensin II receptor blockers for the treatment of hypertension

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.     

Long-term prophylaxis in bipolar disorder

Bipolar disorder is a major cause of disability, and the prevention of relapse is a key management goal. Pharmacological interventions, effectively delivered through enhanced clinical care, are central to long-term management.This article summarises the available evidence for a range of pharmacological options, and provides guidance on common issues in clinical management in line with current practice guidelines. The use of medications for long-term prophylaxis should be considered in all patients meeting criteria for bipolar I disorder. Increasing high-quality evidence from randomised trials informs management decisions relating to both novel agents, such as lamotrigine and olanzapine, and longer-established therapies, such as lithium and valproate, in monotherapy. Medications taken long-term in bipolar disorder differ in the extent to which they protect against manic and depressive relapse. Consequently, the emerging challenge is to understand how combination treatments can enhance efficacy and effectiveness based on data from controlled trials rather than random polypharmacy.Clinical care can be enhanced with effective education about the illness, and the use of strategies to improve treatment adherence and the recognition and management of stressors or prodromal symptoms. Where available, a range of specific psychological interventions can be effective as an adjunct to medication.When discontinuation of prophylaxis is necessary, gradual tapering of dose over weeks or months is recommended.     

Medical management of urinary stone disease

Kidney stones occur in approximately 10% of patients in their lifetimes, and > 10 crystal types have been reported in the literature. After treatment, a subset of these patients will have recurrent calculi, leading to significant morbidity and potential for serious chronic renal disease. Detailed metabolic evaluation is indicated in patients at high risk for stone recurrence, as a reversible metabolic abnormality can be identified in > 90% of them. Once the patient's underlying physicochemical and physiologic derangements are defined, targeted medical therapy can be initiated in order to prevent growth of pre-existing stones and new stone formation. In this report, the author provides a comprehensive review of the presently available selective and nonselective pharmacologic treatments for stones. Several exciting investigational pharmaceutical agents for kidney stone prevention are also discussed. Although many of these agents are effective, there remain clinical scenarios in which existing medicines are insufficient.     

Recent advances in antiviral agents: antiviral drug discovery for hepatitis viruses

Hepatitis B virus (HBV)- or hepatitis C virus (HCV)- associated liver diseases are now one of the important health problems in the world because of the high numbers of patients and the serious consequences. Recently, however, relatively effective treatments with antiviral agents have become available. Interferon (IFN), lamivudine and adefovir are now approved for treatment of HBV-associated liver diseases and they have been shown to be fairly effective. The goal of treatments for HBV-associated liver disease is to achieve a clinical cure in as short a period as possible without producing resistance mutation of the virus. Several nucleotide analogues with more potent antiviral activities are now in clinical trials. In the case of HCV-associated liver diseases, Pegylated IFN (Peg IFN) + ribavirin combination therapy is the standard and most effective treatment with a sustained response of 60-70%. The goal of the treatments for these liver diseases is to induce the complete eradication of the infected virus and at present new anti HCV drugs targeting the molecular segments of the virus are under development. It is expected that the complete eradication of infected virus will be possible in most cases in the near future.     

Calcium antagonists in the treatment of hypertension in patients with ischaemic heart disease

Are lives saved or heart attacks prevented by antihypertensive therapy, as a result of blood pressure reduction alone, or because of other properties of the antihypertensive medications which are independent of blood pressure lowering? Long-acting calcium antagonists seem to be as effective as thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors in preventing all-cause mortality and stroke in patients with hypertension, but are probably inferior to ACE inhibitors in preventing coronary artery disease. In patients with symptomatic coronary artery disease, calcium antagonists are generally as effective as β-blockers in relieving angina and improving exercise time-to-onset of angina or ischaemia. Unstable angina or myocardial infarction require treatment with a β-blocker, with an ACE inhibitor added when necessary for blood pressure control or if there is significant left ventricular (LV) dysfunction. If β-blockers are contraindicated and if there is no LV dysfunction, a non-dihydropyridine calcium antagonist can be substituted.