Management of hyperuricemia in gout: focus on febuxostat

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol

A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection

Objectives: \ud Allopurinol is a uric acid lowering drug used in the treatment of gout and the prevention of tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol inhibit xanthine oxidase, which forms uric acid from xanthine and hypoxanthine. Therapeutic drug monitoring is an important option for evaluation and optimization of allopurinol treatment in case of renal impairment, interaction with uricosuric drugs or to verify patient adherence. In this study we developed and validated a simple quantitative assay using reverse phased high-performance liquid chromatography (HPLC) with UV-detection as a method for quantification of allopurinol and oxipurinol in human serum in the presence of different frequently used drugs. - \ud \ud Methods: \ud The HPLC–UV method uses a mobile phase consisting of sodium acetate (0.02 M; pH 4.5), at a flow rate of 1.0 mL/min. Allopurinol and oxipurinol are detected by UV-absorption at 254 nm with a retention time of 9.9 min for oxipurinol and 12.3 min for allopurinol. Aciclovir is used as internal standard. - \ud Results: \ud Validation showed for allopurinol lower and upper limits of quantification of 0.5 and 10 mg/L and for oxipurinol 1 and 40 mg/L, respectively. The assay was linear over the concentration range of 0.5–10 mg/L (allopurinol) and 1–40 mg/L (oxipurinol). Intra- and inter-day precision showed coefficients of variation <15% over the complete concentration range; accuracy was within 5% for allopurinol and oxipurinol. Endogenous purine-like compounds were separated from allopurinol, oxipurinol and aciclovir with a resolution factor >1.5. Exogenous purine-like compounds and co-medication frequently used by gout patients did not hinder the analysis due to the dichloromethane washing step or to low UV-absorpion at 253 nm. Serum levels of 66 patients prescribed allopurinol 300 mg/day were determined using this HPLC–UV method. Measured serum allopurinol and oxipurinol concentrations in clinical practice showed large variability with a range of <0.5–4.3 mg/L for allopurinol and <1.0–39.2 mg/L for oxipurinol, respectively

Intraoperative epidural analgesia for pain relief after lumbar decompressive spine surgery:A systematic review and meta-analysis

Introduction: During lumbar decompressive spine surgery, the epidural space is easily accessible. This intraoperative situation allows surgeons to apply an epidural bolus of analgesia at the end of the surgical procedure. In literature, several papers about the methods and effectiveness of delivering local analgesia during lumbar decompressive spine surgery have been published. Research question: This systematic review and meta-analysis aims to summaries the current literature on the effectiveness and safety of intraoperative epidural analgesia in lumbar decompressive surgery, delivered as a bolus. Material and method: A systematic search was conducted according to the PRISMA guidelines. Inclusion criteria were randomized controlled trials or comparative cohort studies of patients aged 18 years or older who underwent decompressive lumbar spine surgery. Nonsteroidal epidural analgesia had to be administered as a bolus, intraoperatively, as an adjunct to standard analgesia therapy. Primary outcome measures were reduction in postoperative pain scores, analgesics consumption and length of hospital stay. Secondary outcomes were adverse events. Results: Eight studies evaluating the effectiveness of intraoperative epidural analgesia were included. Seven studies reported statistically significant reductions in postoperative VAS-pain scores. Six studies reported a statistically significant decrease in postoperative analgesics consumption. Four studies reported on the length of hospital stay, with no statistically significant difference between study groups. Discussion and conclusion: This systematic review and meta-analysis suggests that additional intraoperative epidural nonsteroidal analgesia, delivered as a bolus, can reduce postoperative pain and postoperative analgesics consumption in patients undergoing decompressive spinal surgery. Further well-powered research is needed to bolster the evidence