The prevention of gastropathy and upper abdominal symptoms caused by nonsteroidal anti-inflammatory drugs

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing, primarily due to arthritis in the aging population. This article reviews current data on the risk of gastrointestinal complications related to NSAIDs and strategies to manage risk in patients taking these agents. Risks of NSAID use include gastrointestinal ulceration, hemorrhage, or perforation; renal dysfunction; death; and dyspepsia. Alternate therapies include use of non-NSAID analgesics; low-dose NSAIDs; and concurrent administration of cytoprotective agents with NSAIDs, acid inhibitors, proton pump inhibitors, and COX-2 agents.     

Calcium channel antagonists part V: Second-generation agents

Summary Second-generation agents include new dihydropyridines, such as amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, and nitrendipine. Verapamil-like agents include tiapamil, gallopamil, and anipamil. Among the diphenylalkylamines, bepridil is of special interest. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. From all these agents will be selected those that are longer-acting and provide higher vascular selectivity.     

New pharmacological agents for the treatment of gastroesophageal reflux disease

Proton pump inhibitors (PPIs) are currently the most effective and most widely used agents for gastroesophageal reflux disease (GERD). Despite the efficacy of these agents in healing and symptom relief, a substantial proportion of patients require twice-daily therapy with PPIs, and break-through symptoms cause others to use over-the-counter antacids and histamine 2-receptor antagonists to supplement their PPI therapy. Major strategies that are being pursued include the development of agents that have a faster onset of action for on-demand therapy; have better control of acid secretion, resulting in improved healing in advanced grades of esophagitis and better symptom control; and agents that decrease transient lower esophageal sphincter relaxations (TLESRs), thereby reducing distal acid exposure and weakly acidic refluxate. A number of new pharmaceutical agents are currently undergoing clinical evaluation for the treatment of GERD. These include agents that reduce TLESRs, serotonergic agents/ prokinetics, long-acting PPIs, mucosal protectants, and antigastrin agents. One or more of these agents may be the future of GERD therapy.     

Osteoporosis therapies Bisphosphonates, SERMs, PTH, and new therapies

Osteoporosis therapies include antiresorptive and anabolic agents. Antiresorptive agents include the bisphosphonates (etidronate, alendronate, risedronate, ibandronate, and off-label use of the intravenous drugs pamidronate and zolendronate), selective estrogen receptor modulators (SERMs) (raloxifene), calcitonin, and estrogens. An anabolic agent, teriparatide (rhPTH 1–34) was released in 2002. New therapies may be available in the coming years, including new SERMs, strontium ranelate, and an antibody to RANK ligand.     

Integrating novel systemic therapies for the treatment of mycosis fungoides and Sézary syndrome

Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome. Allogeneic transplantation is becoming increasing used for younger patients. Novel agents in advanced development include the monoclonal antibody IPH4102,duvelisib,and the new modified formulation of denileukin diftitox. The choice of agents for patients is typically a balance of patient factors (age, co-morbidities, geographic location), relative efficacy and toxicity.     

A Systematic Review of Side Effects of Nucleoside and Nucleotide Drugs Used for Treatment of Chronic Hepatitis B

Although nucleosides and nucleotides have a good safety record for the treatment of hepatitis B, there have been no systematic reviews on this topic. We searched Medline to include studies of the oral antiviral agents for hepatitis B and adverse events, with at least 48 weeks of follow-up from the initiation of treatment with the drug. Important toxicities include nephrotoxicity, myopathy, and resistance. It is often difficult to ascertain whether an adverse effect is from the study drug or the natural progression of the disease. Further safety data are needed for the newer agents and for all agents with regard to patients with decompensated liver disease, renal dysfunction, the elderly, children, and pregnant women.     

Nuclear cardiac imaging

Important developments in the field of nuclear cardiac imaging include increasing use of single-photon emission computed tomography; the availability of pharmacologic stress testing; the introduction of newer technetium-labeled perfusion imaging agents; and a number of other newer imaging agents and imaging techniques. Tomographic imaging improves image quality as well as sensitivity. This improvement is probably more noticeable with pharmacologic stress testing and with the newer technetium agents. A number of pharmacologic stress agents are now being used. These include dipyridamole, adenosine, and dobutamine. In our experience, thallium tomographic imaging during adenosine-induced coronary hyperemia has resulted in a high degree of accuracy in the diagnosis of coronary artery disease. Both 99mTc-sestaMIBI (hexakis-2-methoxyisobutyl-isonitrile) and 99mTc-teboroxime may be used for simultaneous assessment of perfusion and function. These agents, although similar to thallium in many aspects, differ in many other aspects as they differ from each other. For example, sestaMIBI has a long retention time, but teboroxime has a very rapid washout time. Therefore, the imaging protocols using these two agents are considerably different. Assessment of myocardial viability has been an area of interest; specifically, the use of the reinjection technique has improved the ability to differentiate between scar tissue and viable myocardium.     

ISIS 5 possibilities

There are five major therapeutic groups for possible evaluation in the ISIS 5 trial. They include intravenous beta-blocking agents, glucose-insulin-potassium (GIK) therapy, newer anticoagulant and antithrombotic agents (hirudin and Hirulog), newer thrombolytic drugs such as recombinant plasminogen activator (r-PAJ and surfactant and emulsifying agents such as Rheothrx. Many pilot studies are underway. Selection of agents will depend on the scientific interest of collaborating hospitals as well as the agent's safety and efficacy.     

Ischemic heart disease: metabolic approaches to management

The number of patients with coronary artery disease and its risk factors is increasing in Western nations. New treatments for these patients may soon include a class of agents known as the metabolic modulators. This group of agents consists of the partial fatty acid oxidation inhibitors trimetazidine and ranolazine, as well as dichloroacetate, which promotes carbohydrate utilization. Metabolic modulators also include the nutriceuticals L-carnitine and D-ribose. The available evidence regarding the benefits of each of these five agents is reviewed.     

Targeting Nitric Oxide With Drug Therapy

Increasing knowledge of the role of nitric oxide (NO) in physiology and disease has stimulated efforts to target the NO pathway pharmacologically. These therapeutic strategies include NO donors that directly or indirectly release NO and agents that increase NO bioactivity. Traditional organic nitrates such as nitroglycerin, which indirectly release NO, were believed to have limited long-term efficacy and tolerability, chiefly because of nitrate tolerance. Recent studies, however, suggest more effective ways of using these agents and new applications for them. Nicorandil, a hybrid organic nitrate that also activates potassium channels, has demonstrated significant benefits in acute coronary syndromes. Other nitrates are being investigated for use in neurodegenerative diseases. Direct NO donors include NO gas, which is useful in respiratory disorders, and the more recent classes of diazeniumdiolates, sydnonimines, and S-nitrosothiols. Preliminary data suggest that these agents may be effective as anti-atherosclerotic agents as well as in other disease states. In addition, hybrid agents that consist of an NO donor coupled with a parent anti-inflammatory drug, including nonsteroidal anti-inflammatory drugs, have demonstrated enhanced efficacy and tolerability compared with the anti-inflammatory parent drug alone in diverse experimental models. Established drugs that enhance NO bioactivity include antihypertensive agents, particularly angiotensin-converting enzyme inhibitors, calcium channel blockers, and newer vasodilating β-blockers. In addition, 3-methylglutaryl coenzyme A reductase inhibitors (statins) promote NO bioactivity, both through and independent of lipid lowering. The NO-promoting actions of these established drugs provide some insight into their known benefits and suggest possible therapeutic potential.     

Follicular lymphoma: emerging therapeutic strategies

Follicular lymphoma is a diverse disease, both biologically and clinically. Patients may present with indolent, asymptomatic disease or more aggressive, symptomatic disease with high tumor burden. Decision-making to treat in the frontline is based on histology, disease burden and patient symptoms. The general approach should be a combination of rituximab and chemotherapy, traditionally using alkylating agents, with or without an anthracycline, with more recent evidence for the alternative of bendamustine. Relapsed/refractory follicular lymphoma carries similar variability in presentation. Therapeutic options include the same regimens traditionally used for first-line therapy; however, they also include agents, such as bendamustine, bortezomib, lenalidomide and anti-CD20 agents (rituximab, ofatumumab and radioimmunotherapy). Finally, hematopoietic stem cell transplantation (both autologous and allogeneic) remains a useful treatment strategy, although the optimal timing of such approaches requires further clarification.     

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis,assessment and management

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co‐morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti‐depressants, the selective serotonin and noradrenaline re‐uptake inhibitors, anti‐convulsants, opiates, membrane stabilizers, the anti‐oxidant alpha‐lipoic acid and topical agents including capsaicin. Current first‐line therapies for painful DPN include tricyclic anti‐depressants, the serotonin and noradrenaline re‐uptake inhibitor duloxetine and the anti‐convulsants pregabalin and gabapentin. When prescribing any of these agents, other co‐morbidities and costs must be taken into account. Second‐line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone‐controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long‐term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non‐pharmacological approaches. Copyright © 2011 John Wiley & Sons, Ltd.     

The pathogenesis of atheroma and the rationale for its treatment.

Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses, new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets.     

Mechanisms of bone loss and gain in untreated and treated osteoporosis

Conclusion Histomorphometric studies have made an important contribution to our understanding of how pharmacologic interventions affect BMD and bone strength in patients with osteoporosis. For antiresorptive agents, the therapeutic effect is mediated predominantly by suppression of bone turnover; in the case of more potent antiresorptive agents, changes in secondary mineralization also occur that affect BMD and, potentially, bone strength. The mechanisms by which anabolic agents increase BMD and reduce fracture risk include de novo bone formation and induction of a positive remodeling balance. The relationship between BMD and bone strength is influenced by different factors in the case of anti-resorptive and anabolic agents, and the relative antifracture efficacy of the two approaches at both vertebral and non-vertebral sites requires further study.     

Severe acute diarrhea

Acute diarrhea is commonly caused by an infection. Severe acute diarrhea warrants immediate medical evaluation and hospitalization. Indications for stool studies include fever; bloody diarrhea; recent travel to an endemic area; recent antibiotics; immunosuppression; and occupational risks, such as food handlers. Noninfectious causes include inflammatory bowel disease, radiation enteritis, and intestinal ischemia. Management of severe acute diarrhea includes intravenous fluid rehydration and empiric antibiotics. Use of antidiarrheal agents is controversial when invasive pathogens are suspected.     

Indoor air pollution.

This article summarizes the health effects of indoor air pollutants and the modalities available to control them. The pollutants discussed include active and passive exposure to tobacco smoke; combustion products of carbon monoxide; nitrogen dioxide; products of biofuels, including wood and coal; biologic agents leading to immune responses, such as house dust mites, cockroaches, fungi, animal dander, and urine; biologic agents associated with infection such as Legionella and tuberculosis; formaldehyde; and volatile organic compounds. An approach to assessing building-related illness and "tight building" syndrome is presented. Finally, the article reviews recent data on hospital-related asthma and exposures to potential respiratory hazards such as antineoplastic agents, anesthetic gases, and ethylene oxide.     

Non-antiarrhythmic drugs in atrial fibrillation: a review of non-antiarrhythmic agents in prevention of atrial fibrillation

This article reviews current evidence of non-antiarrhythmic agents for the prevention and maintenance of sinus rhythm in patients with atrial fibrillation. These nontraditional agents include angiotensin coverting enzyme inhibitors, angiotensin receptor blockers, antiinflammatory agents, calcium channel blockers, and beta-blockers. The mechanisms of action and clinical trials regarding the effectiveness of these agents in atrial fibrillation prevention are reviewed.     

Treatment of resistant acute myeloid leukemia.

Although combination cytotoxic chemotherapy induces complete remission in 60-80% of adults with previously untreated acute myeloid leukemia, most patients will ultimately relapse and die from leukemia. Strategies which have been developed for patients with relapsed leukemia include the use of active non-cross-resistant chemotherapeutic agents, allogeneic or autologous bone marrow transplantation, or combined sequential therapy with hematopoietic growth factors and chemotherapy. Most salvage chemotherapeutic regimens use high-dose cytarabine; other agents which have activity include idarubicin, mitoxantrone, etoposide, and high-dose cyclophosphamide. Bone marrow transplantation represents the preferred approach for patients with resistant leukemia offering a likelihood of prolonged disease-free survival. Unique combinations of high-dose chemotherapy and growth factors may provide an alternative therapeutic role in the treatment of resistant leukemia.     

Newer agents for the treatment of painful diabetic peripheral neuropathy

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies in diabetes. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-D-aspartate receptor antagonists, and the opioid analgesics. The availability of several newer agents, used alone or in combination, has resulted in the successful alleviation of neuropathic pain in many patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities with less prominent side effects.     

Adjuvant antithrombotic therapy in ST-elevation myocardial infarction: A narrative review

This article reviews the major pharmacologic features of, and clinical evidence on, adjuvant medical therapy in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. These drugs include oral antiplatelets (aspirin and P2Y₁₂ inhibitors such as clopidogrel, prasugrel and ticagrelor), intravenous antiplatelet agents (the P2Y₁₂ inhibitor cangrelor, GP IIb/IIIa inhibitors such as abciximab, eptifibatide and tirofiban), and intravenous anticoagulant agents (unfractionated heparin, low molecular weight heparin and bivalirudin).