Opportunities for Reversible Inhibitors of Monoamine Oxidase-a (RIMAs) in the Treatment of Depression.

Opportunities for reversible inhibitors of monoamine oxidase-A (RIMAs) in the treatment of depression.

CNS Spectr. 2012 Sep; 17(3): 107-20
Lum CT, Stahl SM

Treatment-resistant depression (TRD) may be implicated in 33–57% of depression cases. The currently available effective treatments include electroconvulsive therapy (ECT) or augmentation of serotonin selective reuptake inhibitors (SSRIs) with antipsychotics. ECT and antipsychotics are both associated with safety and tolerability concerns. Depression is hypothesized to result from a dysregulation of monoamine neurotransmitters, although the source of the dysregulation has been unclear. However, recent studies have revealed that an enzyme that degrades the neurotransmitters, known as monamine oxidase-A (MAO-A), may be overactive in patients with depression. Thus, treatments for depression that modulate MAO-A could act upstream relative to current antidepressant treatments. Monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders. Some evidence suggests that MAOIs may act by reversing excessive neurotransmitter depletion within the neuron and the synapse. MAOIs tend to be underutilized in clinical practice, due in part to misinformation and mythology about their dietary and drug interactions. The new class of reversible monoamine oxidase inhibitors (RIMAs) has shown efficacy in depression, with safety and tolerability comparable to SSRIs. This article discusses recent progress in RIMAs toward the treatment of TRD. Dietary and drug interactions of MAOIs will be covered, as well as guidelines for integrating these agents into clinical practice. HubMed – drug

Ramadan and Sport: Minimizing Effects Upon the Observant Athlete.

Sports Med. 2013 Jul 26;
Shephard RJ

The intermittent fasting of Ramadan could affect various aspects of body physiology and biochemistry important to athletic success. Much of the available information on this subject has been collected from sedentary subjects or low-level competitors, often without well matched controls. Other issues requiring clearer definition include the duration of fasting, the local environment, the timing of observations, and changes in training, diet and sleep patterns. Sleep may be shortened or made good with daytime naps. Circadian rhythms of temperature, metabolism, hormonal secretions and physical performance may be disrupted and incidental activities curtailed. Disturbances of psychomotor performance include daytime sleepiness, impaired vigilance and slower reactions. Food intake is limited to night-time meals. Sedentary individuals sometimes exploit Ramadan to reduce body fat stores. Well disciplined athletes usually maintain energy balance unless daily energy expenditures are very high. Protein intake must allow for gluconeogenesis, and provide quality protein ingested around training times. Blood sugar levels are likely to fall over a long and active day, even if morning glycogen reserves are maximized. Metabolism of fat should be encouraged, beginning prior to Ramadan; inclusion of fat in the pre-dawn meal also slows gastric emptying. Daytime fluid depletion is inevitable if athletes exercise in the heat, but the immediate deficit can usually be made good at night. Some studies show an initial fluid depletion, with recovery as Ramadan continues, possibly reflecting changes in urine and sweat production. Top athletes can maintain training throughout Ramadan, although coaches sometimes reduce demands through a pre-competitive tapering of effort. Late night or early morning training requires negotiation with players who are not observing Ramadan, and dietary adjustments to maintain optimal plasma amino acid levels when training. Performance of repeated anaerobic exercise is impaired, but aerobic power and muscular strength show little change during Ramadan. Ratings of fatigue are increased, and vigilance and reaction times are impaired, particularly during the afternoon. Medical issues during Ramadan are few. Athletes with diabetes mellitus should seek a medical exemption from fasting, and prescribed drug schedules should be carefully maintained. There is no major increase of injury rates, but competitors may have difficulty in producing urine for doping controls. Logical measures to minimize the effects of Ramadan include the optimization of mood state, maintenance of training, minimization of sleep loss, appropriate adjustments of diet, and the monitoring of competitors for chronic dehydration. Future research should concentrate on the changes observed in top athletes, particularly women, with data collected in the late afternoon after a known period of fasting in a well defined environment. It will be important to ensure that the lifestyle of those studied has been optimized. Implications of chronic dehydration for doping control also merit further investigation. Current data suggest that the impact of Ramadan upon athletic performance is small relative to the precision of test procedures, although it may be sufficient to cause a loss of medals. Negative effects vary widely with the type of sport, the season when fasting is observed, the local culture and the discipline exercised by the athlete. HubMed – drug

Opioids for acute pancreatitis pain.

Cochrane Database Syst Rev. 2013 Jul 26; 7: CD009179
Basurto Ona X, Rigau Comas D, Urrútia G

Acute pancreatitis is an acute inflammatory process of the pancreas that may also involve adjacent tissues and/or remote organ systems. Abdominal pain is the main symptom and is usually accompanied by nausea, vomiting and fever. Opoids are commonly used to manage pain in acute pancreatitis but there are still some uncertainties about their clinical effectiveness and safety.To assess the effectiveness and safety of opioids for treating acute pancreatitis pain.The search strategy included the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 6), MEDLINE (from 1950 to June 2013) and EMBASE (from 1980 to June 2013). There were no restrictions by language or publication status.We considered randomised clinical trials (RCTs) assessing the effectiveness of any opioid drug used for treating acute pancreatitis pain.Two review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RRs) for dichotomous data and calculated a 95% confidence interval (CI) for each RR. We performed an intention-to-treat (ITT) analysis. We undertook meta-analysis for some outcomes.We included five RCTs with a total of 227 participants (age range 23 to 76 years; 65% men) with acute pancreatitis pain. The opioids assessed were intravenous and intramuscular buprenorphine, intramuscular pethidine, intravenous pentazocine, transdermal fentanyl and subcutaneous morphine.One RCT, comparing subcutaneous morphine with intravenous metamizole reported non-significant reduction in the number of participants with improvements in pain intensity (primary outcome) (RR 0.50, 95% CI 0.19 to 1.33). Three studies compared analgesia using opioids with non-opioid treatments. After excluding one study that used opioids through continuous intravenous infusion, there was a decrease in the number of patients requiring supplementary analgesia (RR 0.53, 95% CI 0.30 to 0.93). In a single study, there were no differences in the number of patients requiring supplementary analgesia between buprenorphine and pethidine (RR 0.82, 95% CI 0.61 to 1.10).Pancreatitis complications were not associated with a significant difference between the drugs tested. No clinically serious or life-threatening adverse events occurred related to treatment. No differences for this outcome were found between opioid and non-opioid treatments, or for type of adverse event (nausea-vomiting and somnolence-sedation). One death in the procaine group was reported across all the trials.One RCT comparing pethidine with intramuscular buprenorphine reported non-significant differences of supplementary analgesic, adverse events or deaths. One RCT comparing fentanyl with placebo found no difference in adverse events.The findings of this review are limited by the lack of information to allow full appraisal of the risk of bias, the measurement of relevant outcomes and the small numbers of participants and events covered by the trials.Opioids may be an appropriate choice in the treatment of acute pancreatitis pain. Compared with other analgesic options, opioids may decrease the need for supplementary analgesia. There is currently no difference in the risk of pancreatitis complications or clinically serious adverse events between opioids and other analgesia options.Future research should focus on the design of trials with larger samples and the measurement of relevant outcomes for decision-making, such as the number of participants showing reductions in pain intensity. The reporting of these RCTs should also be improved to allow users of the medical literature to appraise their results accurately. Large longitudinal studies are also needed to establish the risk of pancreatitis complications and adverse events related to drugs. HubMed – drug

Tendon Injury and Fluoroquinolone Use: A Systematic Review.

Drug Saf. 2013 Jul 26;
Stephenson AL, Wu W, Cortes D, Rochon PA

Fluoroquinolone antibiotics are commonly used to treat infections and are prescribed by general practitioners, medical specialists and surgeons. Tendon injury has been associated with the use of these medications but the risk associated with newer fluoroquinolones has not been established.The aim of this systematic review was to evaluate the evidence from observational studies to determine the strength of the association between fluoroquinolone use and tendinopathy, and to identify risk factors for this complication.We searched MEDLINE, EMBASE and the Cochrane Collaboration from inception through May 2013 to identify observational studies focused on tendon injury and fluoroquinolones. Studies with original data were selected for inclusion following the PRISMA guidelines. Of the 560 abstracts screened, 16 relevant studies were independently rated by three authors (WW, AS, DC) using the Newcastle-Ottawa Quality Assessment Scale, and assigned a quality score out of 9. High-quality studies (i.e. scored 4.5 or higher) are summarized in detail in this article. Data were independently extracted by two authors (WW, AS).Overall, 16 studies were included in our study. Eight were deemed to be of high quality and five specifically evaluated Achilles tendon rupture. In addition, three studies examined Achilles tendinitis, and three included tendon disorders (including any tendon rupture) as an outcome. Results from these studies suggest that individuals exposed to fluoroquinolones are at increased risk for Achilles tendon rupture, particularly within the first month following exposure to the drug (odds ratios ranged from 1.1 to 7.1). One study showed an increased risk of tendon rupture in those over 60 years of age. Five studies stated that individuals taking fluoroquinolones and oral corticosteroids are at increased risk for tendon injury compared with those taking fluoroquinolones alone. Four studies examined the differential effect of a limited number of fluoroquinolones. Ofloxacin had the highest risk of tendon injury in three of the studies.Included studies are observational in nature and rely on self-report, which may lead to misclassification or underestimation of tendon injury.Observational studies showed an increased risk of tendon injury, including tendon rupture and tendinitis, with exposure to fluoroquinolone antibiotic therapy. Although this complication appears to be rare, concomitant corticosteroids increase the risk for tendon injury, which varies depending on the fluoroquinolone used. HubMed – drug