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Gastrointestinal Side Effects (gastrointestinal + side_effects)
Selected AbstractsCYP2D6 polymorphism and clinical effect of the antidepressant venlafaxineJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2006M. E. E. Shams PhD Summary Background:, Venlafaxine (V) is a mixed serotonin and noradrenaline reuptake inhibitor used as a first-line treatment of depressive disorders. It is metabolized primarily by the highly polymorphic cytochrome P450 (CYP) enzyme CYP2D6 to yield a pharmacologically active metabolite, O -desmethylvenlafaxine (ODV), and to a lesser extent by CYP3A4, to yield N -desmethylvenlafaxine (NDV). Objectives:, The aim of this study was to assess whether the O-demethylation phenotype of V has an impact on the pharmacokinetics and clinical outcome. Method:, In 100 patients treated with V, serum concentrations of V, ODV and NDV and the ratios of concentrations ODV/V as a measure of O-demethylation were determined. Individuals exhibiting abnormally high or low metabolic ratios of ODV/V were selected for genotyping. Clinical effects were monitored by the Clinical Global Impressions Scale and side effects by the UKU (Udvalg for Kliniske Undersogelser Side Effect Rating Scale) rating scale. Results:, There was wide inter-individual variability in ODV/V ratios. The median ratio ODV/V was 1·8 and the 10th and 90th percentiles 0·3 and 5·2, respectively. Individuals with ODV/V ratios below 0·3 were all identified as poor metabolizers (PM), with the genotypes *6/*4 (n = 1), *5/*4 (n = 2) or *6/*6 (n = 1). Individuals with ratios above 5·2 were all ultra rapid metabolizers (UM, n = 6) due to gene duplications. Five individuals with intermediate metabolic activity (ODV/V, 1·1 ± 0·8) were heterozygotes with the CYP2D6*4 genotype, and one patient with an intermediate metabolic ratio of 4·8 had the genotype *4/2x*1. Clinical outcome measurements revealed that patients with ODV/V ratios below 0·3 had more side effects (P < 0·005) and reduced serum concentrations of sodium (P < 0·05) in comparison with other patients. Gastrointestinal side effects, notably nausea, vomiting and diarrhoea were the most common. Differences in therapeutic efficacy were not significant between the different phenotypes. Conclusion:, The O-demethylation phenotype of V depends strongly on the CYP2D6 genotype. A PM phenotype of CYP2D6 increases the risk of side effects. [source] Medium-chain triglyceride (MCT) ketogenic therapyEPILEPSIA, Issue 2008Yeou-mei Christiana Liu Summary The medium-chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD. [source] Prophylaxis of Hemicrania Continua: Two New Cases Effectively Treated With TopiramateHEADACHE, Issue 3 2007Filippo Brighina MD Hemicrania continua (HC) is an uncommon and under-recognized primary headache disorder characterized by a strictly unilateral continuous headache of moderate intensity with possible exacerbations and associated with ipsilateral autonomic features. HC has generally a prompt and enduring response to indomethacin although 25% to 50% of treated patients develop gastrointestinal side effects. These cases pose a difficult management challenge as no other drug is consistently effective in HC. Recently 2 HC patients responsive to topiramate treatment have been reported. Here we describe 2 more patients effectively treated with topiramate. Neither reported any side effects and one had persisting response for 6 months after drug withdrawal. [source] Primary CMV Infections Are Common in Kidney Transplant Recipients After 6 Months Valganciclovir ProphylaxisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010I. Helanterä Prolonging cytomegalovirus (CMV) prophylaxis in CMV seronegative recipients of a kidney from CMV seropositive donor (D+/R,) may reduce the incidence of late infections. We analyzed late-onset primary CMV infections after 6 months valganciclovir prophylaxis. Data from all CMV D+/R, kidney transplant recipients between January 2004 and December 2008 at our center were analyzed. Patients with a functioning graft at 6 months after transplantation who received 6 months of valganciclovir prophylaxis 900 mg once daily were included (N = 127). CMV was diagnosed with quantitative PCR. Prophylaxis was completed in 119 patients. Prophylaxis was stopped at 3,5 months due to leukopenia or gastrointestinal side effects in eight patients. Late-onset primary CMV infection developed in 47/127 (37%) patients median 244 days after transplantation (range 150,655) and median 67 days after the cessation of prophylaxis (range 1,475). Four infections were asymptomatic. In others, symptoms included fever (N = 28), gastrointestinal symptoms (nausea, vomiting, diarrhea) (N = 24), respiratory tract symptoms (N = 12), and hepatopathy (N = 6). Median peak viral load was 13500 copies/mL (range 400,2 831 000). Recurrent CMV infection developed in 9/47 (19%) patients. No significant risk factors for CMV infection were identified. Symptomatic primary CMV infections were commonly detected also after prolonged valganciclovir prophylaxis. [source] Treatment of rheumatoid arthritis with a syk kinase inhibitor: A twelve-week, randomized, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 11 2008Michael E. Weinblatt Objective Spleen tyrosine kinase (Syk) has been identified as an important modulator of immune signaling in B cells and cells bearing Fc,-activating receptors. R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). Methods We enrolled 189 patients with active RA despite methotrexate therapy in a 3-month, multicenter, ascending-dose, double-blind, placebo-controlled trial. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Results Twice-daily oral doses of 100 mg and 150 mg of R788 were significantly superior to placebo or twice-daily oral doses of 50 mg at week 12 (ACR20 achieved in 65% and 72% versus 38% and 32% of patients, respectively [P < 0.01]). ACR50 (achieved in 49% and 57% versus 19% and 17% of patients, respectively) and ACR70 (achieved in 33% and 40% versus 4% and 2% of patients, respectively) scores showed a similar pattern. Clinical effect was noted as early as 1 week after initiation of therapy. Reductions in serum interleukin-6 and matrix metalloproteinase 3 levels also occurred as early as week 1 in the groups receiving 100 mg and 150 mg R788. The major adverse effects were gastrointestinal side effects (predominantly diarrhea) and neutropenia (<1,500/mm3), both of which were dose related. Conclusion These results indicate that an inhibitor of Syk kinase produces significant clinical benefits at 12 weeks in a population of patients with active RA receiving methotrexate therapy. Syk kinase may be an important new therapeutic target in RA and related autoimmune conditions. [source] A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriageBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2005F. Blohm Objectives To study if misoprostol 400 ,g, administered vaginally, increased the successful resolution of early miscarriage compared with placebo. Design Randomised, double blind placebo controlled study. Setting Sahlgrenska University Hospital, Göteborg, Sweden. Sample One hundred and twenty-six women seeking medical attention for early miscarriage. Method Women with a non-viable, first trimester miscarriage were randomised to vaginal administration of misoprostol 400 ,g or placebo. Main outcome measures Main outcome measure was the proportion of successful complete resolution of miscarriage. Secondary outcomes were incidence of infection, bleeding, gastrointestinal side effects, pain, use of analgesics and length of sick leave between groups. Results Sixty-four patients were randomised to misoprostol and 62 to placebo. Eighty-one percent in the misoprostol and 52% in the placebo group had a complete miscarriage within one week of the primary visit (RR 1.57; 95% CI 1.20,2.06). Patients in the misoprostol group reported more pain as assessed on a visual analogue scale (60.4 [31.0] vs 43.8 [37.1] mm; P < 0.007) and required analgesics more often (83%vs 61%, RR 1.35; 95% CI 1.08,1.70). There were no significant differences in the occurrence of gastrointestinal side effects, infection, reduction in haemoglobin or sick leave between the groups. Conclusions Treatment with 400 ,g misoprostol administered vaginally increased the success rate of resolvement of uncomplicated early miscarriages compared with placebo. However, women who received misoprostol experienced more pain and required more analgesics than those who did not. [source] Poor tolerability of high dose ascorbic acid in a population of genetically confirmed adult Charcot-Marie-Tooth 1A patientsACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009C. TothArticle first published online: 22 DEC 200 Background,,, Preclinical studies have suggested that ascorbic acid (AA) treatment in a mouse model of Charcot-Marie-Tooth type 1A (CMT1A) improves motor function and prolongs lifespan. Aims,,, I sought to determine the safety and tolerability of AA in adult patients with CMT1A. Methods,,, An open-label cohort-controlled 2-year pilot study was used to evaluate the tolerability of 5 g of AA daily. Secondary measurements consisted of clinical and electrophysiological measurements at 0, 12, and 24 months in CMT1A patients. Results,,, Twelve CMT1A patients received AA and 10 CMT1A patients formed a cohort group followed in identical manner. Five (42%) patients tolerated this dose of AA for the entire 2-year span, with six patients (50%) developing intolerable gastrointestinal side effects. No significant differences in clinical, disability, or electrophysiological measurements occurred between baseline and final follow-up in patients receiving AA when compared with cohorts. Conclusions,,, High dose AA was not well tolerated in all adult CMT1A patients who may be susceptible to gastrointestinal adverse effects of AA. Studies with greater powers to detect efficacy will be required to test the validity of AA as a therapy in CMT1A patients. Doses lower than 5 g of AA daily may be required for maintenance of tolerability in the CMT1A population. [source] Colesevelam: Potential Uses for the Newest Bile ResinCARDIOVASCULAR THERAPEUTICS, Issue 1 2005Karen L. Steinmetz ABSTRACT Colesevelam is the newest bile resin with a unique chemical structure. It binds to bile acids with higher affinity than traditional bile acid sequestrants and has fewer gastrointestinal side effects and drug interactions. Colesevelam is safe and efficacious alone or in combination with HMG-CoA reductase inhibitors (statins) in reducing low-density lipoprotein cholesterol (LDL-C) levels. Despite this, the role of colesevelam in the treatment of hyperlipidemia remains limited, particularly in the face of new lipid lowering agents. As guidelines for cholesterol control become more stringent, the need to maximize therapeutic benefit through combination therapy will become increasingly more important. Colesevelam has a dose-sparing effect on statin therapy, potentially decreasing the risk of unwanted side effects or drug-drug interactions associated with statin use. This makes colesevelam a viable option for addition to a statin regimen when goal LDL-C levels cannot be achieved with a statin alone. Additionally, anecdotal reports indicate that colesevelam may have potential benefits in certain patient populations that cannot tolerate other lipid lowering therapies, including organ transplant recipients, cholestatic liver disesase, and end-stage renal disease. By recognizing the potential utility of colesevelam, clinicians can better manage those patients who are not able to tolerate first-line therapies. [source] | ||||||||||