{"title":"Safety and Efficacy of Ivabradine in the Management of Stable Angina Pectoris","authors":"J. Tardif","doi":"10.4137/CMT.S1086","DOIUrl":"https://doi.org/10.4137/CMT.S1086","url":null,"abstract":"The first selective If current inhibitor, ivabradine, lowers heart rate (HR) at rest and during exercise with no vasomotor, negative inotropic, or negative lusitropic effects. Given that elevated resting HR is a key factor in the onset of myocardial ischemia and a strong independent predictor of cardiovascular outcomes, ivabradine provides new therapeutic prospects in coronary artery disease (CAD). Its selective HR-lowering action has proven anti-ischemic and anti-anginal efficacy, and ivabradine is currently indicated for the symptomatic treatment of stable angina pectoris. Ivabradine can also be safely combined with other anti-anginal agents, and addition of ivabradine to beta-blocker therapy further improves anti-ischemic efficacy and exercise capacity of patients with stable angina. The recent BEAUTIFUL trial demonstrated that although the primary endpoint was not met in the overall population, addition of ivabradine on top of standard preventive treatments significantly reduced the risk of coronary events in stable CAD patients with left ventricular systolic dysfunction among the subgroup of patients with a resting HR ≥ 70 bpm. This is in accordance with pre-clinical data showing that long-term HR reduction improves endothelial function and reduces the progression of atherosclerosis. A significant proportion of patients with stable angina have elevated resting HR and ivabradine should therefore be considered as an important therapy in these cases. In combination with other standard treatments, ivabradine can improve angina and could potentially improve coronary outcomes. Ongoing and future clinical studies will evaluate the presence and magnitude of the cardio-protective benefits of HR lowering with ivabradine in patients with cardiovascular diseases.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81818462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dexlansoprazole MR in the Management of Gastroesophageal Reflux Disease","authors":"K. Olsen, Margaret L. Hitzeman","doi":"10.4137/CMT.S2538","DOIUrl":"https://doi.org/10.4137/CMT.S2538","url":null,"abstract":"Dexlansoprazole MR, an enantiomer of lansoprazole, is a unique proton pump inhibitor with a duel release mechanism. This release mechanism produces two distinct peak concentrations that result in a prolonged mean residence time with increased duration of plasma concentrations and a greater percent time the pH is maintained above 4. The prolonged residence time allows dexlansoprazole MR to be administered throughout the day without regards to meals or the timing before a meal. In two trials of patients with erosive esophagitis, dexlansoprazole MR 60 mg and 90 mg demonstrated comparable healing rates to lansoprazole 30 mg. In patients with healed EE, dexlansoprazole MR 30 mg (75%) and 60 mg (83%) were superior to placebo (27%; p < 0.0025) in maintenance of healing. Dexlansoprazole MR 30 mg and 60 mg had a greater percentage of heartburn-free days (91%–96%) and heartburn-free nights (96%–99%) than placebo (29%–72%) over the 6-month maintenance trial. Dexlansorpazole MR appears to be well tolerated with the safety profile being similar to lansoprazole with gastrointestinal adverse events being the most common. Dexlansoprazole MR provides a new treatment option for gastroesophageal reflux disease due to the flexible dosing, the unique release mechanisms and prologned pharmacodynamic effect.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84536751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacotherapy of Fibromyalgia: Focus on Duloxetine","authors":"E. Serra, M. Andréjak","doi":"10.4137/CMT.S1162","DOIUrl":"https://doi.org/10.4137/CMT.S1162","url":null,"abstract":"Context: Fibromyalgia syndrome (FMS) is a frequent medical condition characterized by chronic widespread pain and reduced pain threshold. Associated symptoms include fatigue, non restorative sleep, and psychological distress. As usual in medicine, even if the pathogenesis is unclear, some treatments are useful to help patients. \u0000 \u0000Objectives: Tricyclic antidepressants were the first drugs used to treat FMS. More recently, among serotonin-norepinephrine reuptake inhibitors, duloxetine was approved by US Food and Drug Administration to treat FMS. Duloxetine is used for the management of major depressive disorder, neuropathic pain, generalized anxiety disorder, and stress incontinence. In the pharmacotherapy of fibromyalgia, a focus is presented on the drug duloxetine. \u0000 \u0000Results: Mechanism of action, metabolism and pharmacokinetic profile are presented. Clinical studies of Duloxetine showed an acceptable efficacy for this chronic condition: Number Need to Treat (NTT) of 4.7 to 9.9, through two 3-month placebo-controlled trials and two 6-month trials. Evaluation criteria are discussed. Safety of this medication has been found to be satisfactory, with nausea as the most common adverse event, in almost 20% of cases. \u0000 \u0000Conclusion: Treatment algorithm for duloxetine is presented inside FMS treatment strategy. With duloxetine, it is important to start low and increase slowly to prevent or minimize adverse events: 30 mg/day up to 60 mg/day in the second week and if necessary up to 90–120 mg/day. It is possible to treat for 3 to 6 months, possibly up to 12 months. The drug could be decreased 2 to 4 weeks before stopping, with regular assessments during this time. International recommendations insist on multimodal treatments: drug and non drug. Also effective for anxiety and depression, duloxetine ranks among the first place drugs for FMS.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84231752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safety and Efficacy of Cefazolin Sodium in the Management of Bacterial Infection and in Surgical Prophylaxis","authors":"T. Kusaba","doi":"10.4137/CMT.S2096","DOIUrl":"https://doi.org/10.4137/CMT.S2096","url":null,"abstract":"Cefazolin sodium is a first-generation cephalosporin antibiotic and has been used worldwide since the early 1970s. It is used for the treatment of bacterial infections in various organs, such as the respiratory tract, skin and skin structure, genital tract, urinary tract, biliary tract, and bone and joint infections. It has also been used for septicemia due to susceptible gram-positive cocci (except Enterococcus), some gram-negative bacilli including E. coli, Proteus, and Klebsiella may be susceptible, and for perioperative prophylaxis. After the introduction of penicillins and other cephalosporins, occasional outbreaks of methicillin-resistant Staphylococcus aureus were noted. As a result, vancomycin use was increased; however, very recently and most alarmingly, vancomycin-resistant strains have been described. In this setting, to avoid the risk of the development of vancomycin-resistant strains further, vancomycin use should be curtailed. In consideration of this historical background, the appropriate use of antibiotics, such as dosage, dosage intervals, and the duration of administration is required not only for the protection of patients’ health but also for the prevention of the development of drug resistance. Cefazolin has been used in clinical practice for about 40 years, and a large body of evidence has been accumulated, and its efficacy and safety are well established compared with other antibiotics. Therefore, cefazolin has been chosen as a first-line anti-microbial for prophylaxis after various surgical procedures, including cardiovascular surgery, hysterectomy, arthroplasty and so on. Based on these facts, especially for the prophylaxis of surgical site infections, the first-generation cephalosporin, cefazolin, is now being “re-visited”.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79443855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bevacizumab: Review of Development, Pharmacology, and Application to Brain Tumors","authors":"H. Newton","doi":"10.4137/CMT.S2042","DOIUrl":"https://doi.org/10.4137/CMT.S2042","url":null,"abstract":"Bevacizumab is a humanised monoclonal antibody targeted to the vascular endothelial growth factor (VEGF). VEGF is the ligand for VEGF receptors (VEGFR), which are important for the development and maintenance of the angiogenic phenotype in high-grade solid tumors, including malignant gliomas. An overview of angiogenesis, VEGF, VEGFR, and the pharmacology of bevacizumab will be presented. Bevacizumab is active in pre-clinical testing against glioma tissue cultures and xenograft models. In the clinical setting, in combination with irinotecan and other chemotherapy agents, it has shown significant activity in patients with glioblastoma multiforme (GBM) and other brain tumors. Objective responses on neuro-imaging have been noted in 30%–60% of reported cases. Prolongation of progression-free survival and overall survival have also been suggested in many reports. Treatment of bevacizumab is associated with potential side effects, including thromboembolic disorders, fatigue, intracranial hemorrhage, proteinuria, hypertension, and bowel perforation.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84277626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteasome Inhibition: Thinking Outside the Box","authors":"M. B. Armstrong","doi":"10.4137/CMT.S3072","DOIUrl":"https://doi.org/10.4137/CMT.S3072","url":null,"abstract":"A new era in cancer therapy is emerging with the development of tumor-specific agents exhibiting less toxicity. Since the advent of imatinib, several tumor-directed treatment options have been developed. However, therapies not directed specifically at a tumor target also have potential benefits. The 26S proteasome is a critical regulator of cell homeostasis through the degradation of key signaling molecules including p21, p27, and p53. Additionally, the proteasome degrades I-kB which inhibits the activity of NF-kB, an important promoter of cell proliferation. Blocking function of the proteasome disrupts tumor growth by shifting the balance of the cell from proliferation to apoptosis. In vitro, the proteasome inhibitor, bortezomib, inhibits NF-kB activity and prevents growth of several malignant cell types including multiple myeloma. Given the central role of NF-kB in the pathogenesis of multiple myeloma, bortezomib was a good candidate for use in therapy. Treatment of heavily pre-treated patients with bortezomib led to response rates of 30%–40%. More importantly, bortezomib led to improvements in bone metabolism, a major cause of morbidity in multiple myeloma. This effect was seen independent of the response of the myeloma. This finding correlates with in vitro studies which demonstrate increased BMP2 expression and osteoblast number after exposure to bortezomib. Moreover, bortezomib blocks NF-kB-mediated angiogenesis and tumor cell metastasis. While tumor-targeted treatments have an important role in the future of cancer therapy, these examples show that it is important not to lose sight of the benefits of less-specific agents in the treatment of malignant neoplasms.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73094501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions","authors":"Jubin Ryu, F. C. Yang","doi":"10.4137/CMT.S1969","DOIUrl":"https://doi.org/10.4137/CMT.S1969","url":null,"abstract":"Imiquimod (trade name Aldara™) is a small molecule of the imidazoquinoline family, a group of nucleoside analogs that were first synthesized as potential antiviral agents. It has since been discovered to activate both innate and adaptive immunity, as well as apoptosis. Clinically, it has been approved for three indications thus far: external genital warts, actinic keratosis, and superficial basal cell carcinoma. In addition to these applications, a number of off-label uses have been reported in the literature. In this review, we summarize and discuss the literature describing imiquimod’s mechanism of action, its approved and off-label clinical uses, and its safety and tolerability.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74777556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacotherapy of Major Depressive Disorder: Focus on Duloxetine","authors":"K. Muneoka","doi":"10.4137/CMT.S1988","DOIUrl":"https://doi.org/10.4137/CMT.S1988","url":null,"abstract":"The serotonin-noradrenaline reuptake inhibitor duloxetine is a second-generation antidepressant for the treatment of major depressive disorder (MDD). Its inhibitory potency for serotonin (5-HT) and noradrenaline (NA) reuptake has been demonstrated in animal and in vitro studies. Human studies of peripheral markers of neurotransmission show inhibition of 5-HT reuptake by duloxetine and also support its potency in NA reuptake inhibition. Moreover, a positron emission tomography study in human brains shows that therapeutic doses of duloxetine result in .80% occupancy of 5-HT transporters. Duloxetine is metabolized by hepatic enzymes and cytochromes P450 CYP2D6 and CYP1A2, and plasma duloxetine concentrations increase linearly according to oral dose. In double-blind, randomized, placebo-control studies of MDD, duloxetine-treated patients show significantly increased response and remission rates and significantly longer time to relapse compared to placebo-treated patients. Moreover, duloxetine is efficacious for the treatment of generalized anxiety disorder (GAD) and pain-related diseases such as diabetic peripheral neuropathic pain (DPNP). A daily dose of 60 mg daily seems most effective for treating MDD, GAD and DPNP. Duloxetine is similar in efficacy to fluoxetine, paroxetine and escitalopram for MDD, although escitalopram is better for improving sleep. The most common treatment-emergent side effects of duloxetine are nausea, dry mouth, fatigue and decreased appetite. Studies suggest an association with the incidence of increased sweating or somnolence at higher doses and an association with irritability or anxiety at high plasma levels of duloxetine. Discontinuation rates due to adverse events are higher in patients who receive duloxetine versus placebo in short-term but not long-term studies. Interestingly, there is not a strong correlation between clinical efficacy and plasma levels of duloxetine. Therefore, although duloxetine is safe and tolerated at therapeutic doses of 60–120 mg/day, the dose should be adjusted while the patient is carefully monitored for efficacy and adverse events.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80317811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Time Course Analysis of Aminoglycoside-Induced Elevation of Serum Creatinine","authors":"W. Sweileh","doi":"10.4137/CMT.S3400","DOIUrl":"https://doi.org/10.4137/CMT.S3400","url":null,"abstract":"Objective: The present study aimed to determine the time course of aminoglycoside-induced serum creatinine (SCr) elevation and compare that in patients treated with amikacin (AK) and those treated with gentamicin (GM). \u0000 \u0000Methodology: A one-year, non-interventional prospective study of patients with normal baseline renal function and were administered either GM or AK. The study was carried out at the internal medicine department of Al-Watani governmental hospital. Outcome of interest was the time course of serum creatinine elevation during the course of aminoglycoside therapy. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS 16). \u0000 \u0000Results: The study was performed in 94 patients, who had to be administered GM or AK by intravenous injections. In both groups, the significant rise in SCr was detected on the 4th day of therapy. However, GM induced up to 32% increase while AK induced up to 19.5% increase in SCr from baseline levels. In the course of AK treatment, patients on single dosing frequency and those <65 years of age did not show a significant increase in SCr levels during the 6-day therapy. In the course of GM therapy, patients on single frequency dosing, younger patients and females showed a significant elevation in SCr on the 5th day while elderly, males and those on multiple dosing showed a significant elevation on the 4th day of therapy. However, all patient categories on GM therapy showed similar extent of SCr elevation. \u0000 \u0000Conclusion: In patients with normal renal function, GM and AK showed similar time course but different extent of SCr elevation. Amikacin induced no SCr elevation when given in single dosing frequency or when given to younger patients. Such effects were not observed with GM.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81091682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fixed-dose Combination Therapy in Hypertension: Focus on Fixed-dose Combination of Amlodipine and Valsartan (Exforge ® )","authors":"S. Aslam","doi":"10.4137/CMT.S1982","DOIUrl":"https://doi.org/10.4137/CMT.S1982","url":null,"abstract":"Hypertension is the leading cause of disability and cardiovascular mortality world-wide. Approximately one-third of the US adult population and over a billion people world-wide have hypertension. Despite increased awareness of hypertension and availability of many effective antihypertensive agents, only one third of patients achieve their target blood pressure (BP). All expert panels now recommend use of combination therapy for stage 2 and higher hypertension and for individuals who are at increased risk of cardiovascular disease (CVD). Amlodipine, a dihydropyridine calcium channel blocker and Valsartan, an angiotensin II receptor (AT1-R) antagonist are widely used antihypertensive agents. Their efficacy in lowering systolic and diastolic BP and reducing CVD events has been demonstrated in several randomized trials. Fixed-dose combination of amlodipine and valsartan (A/V) has been shown to be more effective in lowering BP than monotherapy with either of these agents alone in randomized trials with comparable side effect profile. Approximately 80%–90% of patients with stage 1–2 hypertension receiving A/V fixed-dose combination achieve significant response, defined as a mean sitting diastolic BP 10 mmHg reduction from the baseline. Subgroup analyses show that A/V fixed-dose combination is equally effective in older individuals (>65), Blacks, in patients with isolated systolic hypertension, and in those who fail monotherapy. Furthermore, A/V fixed-dose combination is well tolerated and simplifies antihypertensive regimen enhancing patient adherence and a better BP control compared to monotherapy.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84986030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}