Recent advances in pharmacotherapy of glaucoma

Glaucoma is a slow progressive degeneration of the retinal ganglion cells (RGCs) and the optic nerve axons, leading to irreversible blindness if left undiagnosed and untreated. Although increased intraocular pressure is a major risk factor of glaucoma, other factors include increased glutamate levels, alterations in nitric oxide (NO) metabolism, vascular alterations and oxidative damage caused by reactive oxygen species. Glaucoma is the second leading cause of blindness globally, accounting for 12.3% of the total blindness. Glaucoma has been broadly classified as primary or secondary open-angle or angle-closure glaucoma. The primary goal in management of glaucoma is to prevent the risk factor, especially elevated intraocular pressure (IOP), using medications, laser therapy or conventional surgery. The first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective blocker or a prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Cholinergic agonists are considered third-line treatment options. When a single therapy is not sufficient to lower the IOP, a combination therapy is indicated. To enhance the patient compliance, drug delivery systems like electronic devices, ocular inserts, tansdermal and mechanical drug delivery systems have been developed. Use of viscoelastic agents in ophthalmic formulations, emulsions and soluble ophthalmic drug inserts (SODI) enhance patience compliance and ocular drug delivery in patients in long-term glaucoma therapy. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are recommended. Several nutrients and botanicals hold promise for the treatment of glaucoma, but most studies are preliminary, and larger, controlled studies are required. Future directions for the development of a novel therapy glaucoma may target glutamate inhibition, NMDA receptor blockade, exogenously applied neurotrophins, open channel blockers, antioxidants, protease inhibitors and gene therapy.     

Recent advances in pharmacotherapy of atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with increased morbidity and mortality. Efficacy and safety of currently employed antiarrhythmic drugs (AADs) continue to be less optimal in AF. Development of newer AADs has recently been made possible through a greater understanding of electro-pathophysiology of AF. Highly specific drugs acting on atria are currently being explored, although there is little data available on effectiveness of atrial specific agents in maintaining sinus rhythm. Combining AADs and non-AADs such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase effectiveness of AADs in patients with AF. Controlled clinical trials are required to precisely define the efficacy of single agents versus various combinations in maintaining sinus rhythm in patients with AF. This review describes some of the most promising therapeutic approaches that may overcome some of the limitations of drugs used at present for the management of AF.     

Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate

Jaundice is a common cause for diagnostic works-up and therapeutic intervention in neonates. This is motivated by the risk for severe neurological sequelae (kernicterus). The mainstays of treatment for the past decades have been exchange transfusion and phototherapy. Exchange transfusion is now becoming rare due to immune prophylaxis in Rhesus-negative women, and treatment of sensitised infants with intravenous immunoglobulin. Several different pharmacological approaches have been studied as far as the treatment of neonatal jaundice. Of these, the focus of attention in recent years has been on the haem oxygenase inhibitors (metal meso- and protoporphyrins). These are effective inhibitors of bilirubin production and have been shown to significantly reduce peak serum bilirubin levels in several clinical trials, both when used prophylactically and therapeutically. However, questions remain regarding long-term safety, as well as the advisability of whole-scale inhibition of bilirubin production. Nevertheless, in selected infants with a high risk of severe jaundice, the use of haem oxygenase inhibitors may be acceptable. Pharmacotherapy in jaundiced infants is fraught with risks, as many drugs may increase the entry of bilirubin into the brain and presumably, the risk for neurotoxicity. Both the displacement of bilirubin from its albumin binding and interference with the function of phosphoglycoprotein in the blood–brain barrier are documented mechanisms in this respect.     

Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate

Jaundice is a common cause for diagnostic works-up and therapeutic intervention in neonates. This is motivated by the risk for severe neurological sequelae (kernicterus). The mainstays of treatment for the past decades have been exchange transfusion and phototherapy. Exchange transfusion is now becoming rare due to immune prophylaxis in Rhesus-negative women, and treatment of sensitised infants with intravenous immunoglobulin. Several different pharmacological approaches have been studied as far as the treatment of neonatal jaundice. Of these, the focus of attention in recent years has been on the haem oxygenase inhibitors (metal meso- and protoporphyrins). These are effective inhibitors of bilirubin production and have been shown to significantly reduce peak serum bilirubin levels in several clinical trials, both when used prophylactically and therapeutically. However, questions remain regarding long-term safety, as well as the advisability of whole-scale inhibition of bilirubin production. Nevertheless, in selected infants with a high risk of severe jaundice, the use of haem oxygenase inhibitors may be acceptable. Pharmacotherapy in jaundiced infants is fraught with risks, as many drugs may increase the entry of bilirubin into the brain and presumably, the risk for neurotoxicity. Both the displacement of bilirubin from its albumin binding and interference with the function of phosphoglycoprotein in the blood-brain barrier are documented mechanisms in this respect.     

专家论坛:焦虑症及其治疗药物

传统的药物(如苯二氮(艹卓)类、三环类药物)有很多不良反应10多年来焦虑症药物治疗有了实质性变化,研究证实.SSRI治疗抑郁症和焦虑症是有效和安全的.现在SSSI已成为治疗惊恐障碍的一线药物.同样在广泛性焦虑症的长期治疗中,文拉法辛.帕罗西汀和某些三环类药物优于苯二氮(艹卓)类.作者认为文拉法辛、帕罗西汀、曲唑酮、黛力新以及某些三环类药物可考虑作为广泛性焦虑症的一线药物.苯二氮(艹卓)类药起效快,能立即减轻焦虑症状可短期应用或与SSRI短期联用.     

Frontrunners in novel pharmacotherapy of COPD

The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive process, several new targets have been identified. Several mediator antagonists tested in COPD have been disappointing, but of CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a major limitation so that inhaled delivery will be necessary. Perhaps the most promising approach is reversal corticosteroid resistance through increasing HDAC2 activity. This may be achieved by theophylline-like drugs, more effective antioxidants and non-antibiotic macrolides.     

Recent advances in bipolar disorder pharmacotherapy: focus on bipolar depression and rapid cycling

This article reviews recent advances in the evidence base for effective pharmacotherapy in bipolar disorder. We focus first on bipolar depression, since this pole of the illness forms the bulk of the burden of illness for both bipolar I and bipolar II patients. Recent studies throw doubt on the benefits of antidepressants in bipolar depression and suggest that selected mood stabilizers or second-generation antipsychotics may be effective alternatives. A second focus is on rapid-cycling bipolar disorder, a more severe phase of the illness, in which four or more episodes occur in a year. Although this form of the illness responds poorly to monotherapy, evidence is accumulating concerning which treatments are best combined in order to manage rapid cycling most effectively. Additional nonpharmacological management strategies are a vital element of the effective management of bipolar disorder but are beyond the scope of this review. Finally, suggestions are made for future research.     

Recent trends in pharmacotherapy for anxiety disorders]

Since the introduction of SSRIs, pharmacotherapy for anxiety disorders has significantly changed. Although the SSRIs are considered to be a first-line treatment for the most of anxiety disorders benzodiazepines are still widely used in clinical practice despite the risk of dependence and strong recommendation for their use as a second-line. The SSRIs only replaced tricyclic antidepressants and the MAO inhibitors especially in the treatment of panic disorder, obsessive-compulsive disorder and social phobia. Combination of the SSRIs and the benzodiazepines is widely used. Recently it has been suggested that the combination of SSRI and benzodiazepine is rational, because each drug has a different mechanism of action, the benzodiazepines enhancing GABAergic transmission, and the SSRIs stimulating the 5-HT1A receptor that may inhibit the postsynaptic neuronal excitability in the amygdala and the prefrontal cortex that comprise the brain circuit of fear and anxiety. Recent imaging studies suggested the hyperactivity of the amygdala in the patients with generalized social anxiety disorder and successful treatment with cognitive behavioral therapy or SSRI might significantly reduce the hyperactivity of the amygdala. It was suggested that the rational combination of SSRIs and benzodiazepines seems to be an effective and practical way of treatment for most anxiety disorders.     

Recent advances in kartogenin for cartilage regeneration

Either osteoarthritis or sports-related injuries can lead to cartilage defects, whereas both chondrocyte self-renewal and conventional treatments face limitations. In cartilage regenerative medicine, growth factors are commonly used to induce chondrogenic differentiation of stem cells. However, application of growth factors is confined by some drawbacks. Emerging small molecules are regarded as an alternative for cartilage regeneration. A recently discovered small-molecule compound, kartogenin (KGN), has been proven to be a chondrogenic and chondroprotective agent and is more effective in inducing cartilage regeneration when compared with growth factors. KGN has been processed and applied in many forms, such as in intra-articular injection, in collaboration with growth factors, in incorporation in drug delivery systems, and in combination with scaffolds. Fortunately, progress has been achieved in KGN applications. The current review discusses the recent advances in KGN for cartilage regeneration and thus presents new concepts in cartilage repair in clinical settings.     

抗抑郁药临床应用的进展

抗抑郁药是治疗抑郁症和抑郁症状的主要药物,近10余年来,从药物作用机制到药物的疗效和安全性得到了飞快地发展。使得治疗抑郁症和抑郁症状的药物具有更多的选择,为临床提高疗效、减少药物不良反应和减少疾病复发提供更多的手段。     

Recent advances in nephrology

The 31st Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, USA, October 25-28, 1998, presented the newest advances in basic and clinical nephrology science. Several presentations discussed the results of studies with the newer immunosuppressants such as tacrolimus, sirolimus, mycophenolate mofetil and the anti-CD25 monoclonal antibodies, with the conclusion that studies on long-term use of these agents are needed. A number of other issues on immunosuppression protocols in renal transplantation were addressed during the meeting, including the subjects of steroid withdrawal and the role of TGF-beta in the development of chronic allograft nephropathy. The use of NESP in the treatment of renal anemia, the use of sildenafil to treat erectile dysfunction in hemodialysis patients, and the use of ACE inhibitors in nondiabetic renal patients were other important issues discussed at this meeting. Newer approaches to the treatment of hypertension discussed at the meeting highlighted the potential role of angiotensin II receptor antagonists in renal disease patients. Researchers also presented the promising results of a trial of a new, hybrid cell vaccine approach to the treatment of renal cell carcinoma.     

Recent advances in nephrology

The World Congress of Nephrology was held in Berlin, Germany, June 8-12, 2003. The meeting offered the newest advances in basic and clinical nephrology science and was attended by about 9,000 scientists and clinicians from around the world. During the congress, results of the treatment of Fabry's disease with enzyme replacement therapy, the results of the treatment of anemia in patients with chronic kidney disease with new erythropoietic agents (darbepoetin alfa, continuous erythropoiesis receptor activator), and the management of secondary hyperparathyroidism and calcium-phosphorus disorders in uremia with calcimimetic agents and new phosphate binders, such as lanthanum carbonate, were discussed. Furthermore, recent studies evaluating the efficacy and safety of new immunosuppressive agents and their combination for the treatment of renal transplant recipients were also presented.