Abstract:
BACKGROUND:While cases of amyotrophic lateral sclerosis (ALS) or ALS-like conditions have arisen in apparent association with HMG-CoA reductase inhibitors ('statins') and/or other lipid-lowering drugs (collectively termed 'statins' in this paper for brevity), additional information is needed to understand whether the connection may be causal. The University of California, San Diego (UCSD) Statin Effects Study is a patient-targeted adverse event surveillance project focused on lipid-lowering agents, whose aim is to capitalize on patient reporting to further define characteristics and natural history of statin adverse effects (AEs), and to ascertain whether a patient-targeted surveillance system might lead to presumptive identification of previously unrecognized AEs. ALS was a candidate 'new' AE identified through this process. The aim of the analysis presented here was to examine characteristics and natural history of reported statin-associated ALS-like conditions with attention to factors that may bear on the issue of causality. METHODS:For the present analysis, we focused on cases of statin-associated ALS that were reported to our study group prior to publication of a possible statin-ALS association. Of 35 identified subjects who had contacted the UCSD Statin Effects Study group to report ALS or an ALS-like condition, 18 could not be reached (e.g. contact information was no longer valid). Six were unable to participate (e.g. due to progression of their disease). Of the 11 who could be contacted and were able to participate, one declined to give informed consent. The remaining ten, with either a formal or probable diagnosis of ALS in the context of progressive muscle wasting/weakness arising in association with lipid-lowering drug therapy, completed a mail or phone survey eliciting information about ALS symptom onset and change in association with drug use/modification and development of statin-associated AEs. We reviewed findings in the context of literature on statin antioxidant/pro-oxidant balance, as well as ALS mechanisms involving oxidative stress and mitochondrial dysfunction. RESULTS:All ten subjects reported amelioration of symptoms with drug discontinuation and/or onset or exacerbation of symptoms with drug change, rechallenge or dose increase. Three subjects initiated coenzyme Q10 supplementation; all reported initial benefit. All subjects reportedly developed statin AEs (not indicative of ALS) prior to ALS symptom onset, strongly disproportionate to expectation (p < 0.001). Since this reflects induction of pro-oxidant effects from statins, these findings lend weight to a literature-supported mechanism by which induction by statins of oxidative stress with amplification of mitochondrial dysfunction, arising in a vulnerable subgroup, may propel mechanisms underlying both AEs and, more rarely, ALS. CONCLUSION:A theoretical foundation and preliminary clinical observations suggest that statins (and other lipid-lowering drugs) may rarely be associated with ALS in vulnerable individuals in whom pro-oxidant effects of statins predominate. Our observations have explanatory relevance extending to ALS causes that are not statin associated and to statin-associated neurodegenerative conditions that are not ALS. They suggest means for identification of a possible vulnerable subgroup. Indeed whether statins may, in contrast, confer ALS protection when antioxidant effects predominate merits examination.
journal_name
Drug Safjournal_title
Drug safetyauthors
Golomb BA,Kwon EK,Koperski S,Evans MAdoi
10.2165/00002018-200932080-00004subject
Has Abstractpub_date
2009-01-01 00:00:00pages
649-61issue
8eissn
0114-5916issn
1179-1942pii
4journal_volume
32pub_type
杂志文章相关文献
DRUG SAFETY文献大全abstract:INTRODUCTION:Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. METHODS:Three major types of EHDs in China (i.e., a regional commu...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-017-0589-z
更新日期:2018-01-01 00:00:00
abstract::The treatment of type 2 diabetes mellitus remains controversial. Since most patients are overweight or obese, regimens based on dietary modification and increased physical exercise are logical and safe treatment approaches. However, the long term impact of these interventions is frequently disappointing and pharmacoth...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199921010-00002
更新日期:1999-07-01 00:00:00
abstract::Severe skin adverse drug reactions can result in death, but the rate of such events is fortunately low. The incidences of Stevens-Johnson syndrome and toxic epidermal necrolysis range from 1.2 to 6 per million per year and 0.4 to 1.2 per million per year, respectively. Stevens-Johnson syndrome is fatal in about 5% and...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199513010-00007
更新日期:1995-07-01 00:00:00
abstract::The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.1007/s40264-016-0430-0
更新日期:2016-09-01 00:00:00
abstract::Aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) cause deterioration in respiratory function in approximately 10% of adults with asthma and a smaller proportion of children with asthma. We propose evidence-based guidelines for the safe use of NSAIDs in individuals with asthma foll...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200124110-00004
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:The tumour necrosis factor-alpha inhibitor infliximab is incorporated in the treatment guidelines for patients with inflammatory bowel disease (IBD). However, concerns about serious adverse events such as infections, malignancies and death do exist. OBJECTIVE:To evaluate the occurrence of serious events of ...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/0002018-200831120-00009
更新日期:2008-01-01 00:00:00
abstract::Regular treatment with both long- and short-acting beta 2-agonists results in tolerance to their bronchoprotective effects, although the relevance of this phenomenon in terms of long term asthma control remains unclear. However, there appears to be no appreciable difference between the 2 long-active beta 2-agonists, s...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199716050-00002
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:Hepatic dysfunction, manifested as liver enzyme elevations, occurs frequently in patients who are treated with interferon, however, data for patients with multiple sclerosis are limited. OBJECTIVE:To retrospectively assess the safety profile of interferon-beta-1a therapy with respect to liver function durin...
journal_title:Drug safety
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00002018-200326110-00006
更新日期:2003-01-01 00:00:00
abstract::Data on the efficacy and tolerability of antiretrovirals in children are limited as, in contrast to adult studies, large paediatric cohort studies are lacking. Thus, data pertaining to adults are often extrapolated to children despite the acknowledgement that children are not little adults. This review summarises info...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200225140-00001
更新日期:2002-01-01 00:00:00
abstract:OBJECTIVE:During proton pump inhibitor (PPI) use, in clinical trials, headache is one of the most frequently reported adverse events (frequency 1.3 to 8.8%), while results of one observational study indicate that headache is the fifth most frequently reported adverse event (incidence densities 2.5 to 4.6 per 1000 patie...
journal_title:Drug safety
pub_type: 临床试验,杂志文章
doi:10.2165/00002018-200225040-00005
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:New pharmacovigilance legislation was adopted in the EU in 2010 and became operational in July 2012. The legislation placed an obligation on all national competent authorities (NCAs) and marketing authorisation holders (MAHs) to record and report cases of suspected adverse drug reactions (ADRs) received fr...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-017-0534-1
更新日期:2017-07-01 00:00:00
abstract::Phytoestrogens, plant chemicals classified as isoflavones, coumestans and lignans, display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor beta. They are common components of food items such as grains, beans, fruits and nuts. ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200124090-00003
更新日期:2001-01-01 00:00:00
abstract::Women who discover they are pregnant after exposure to a drug and pregnant women who have a condition that requires continued treatment during pregnancy are told to balance the benefits and risks of the exposure to justify continuation of treatment, discontinuation of treatment or, possibly, pregnancy termination. How...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-200427060-00001
更新日期:2004-01-01 00:00:00
abstract::Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/11587280-000000000-00000
更新日期:2011-06-01 00:00:00
abstract::The electrocardiographic effects of ebastine and its active metabolite, carebastine, have been studied alone and in relevant drug-interaction studies in various patient populations. The overall cardiac tolerability of ebastine is excellent. In ebastine dose-ranging studies in adults and children, there were no meaning...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199921001-00009
更新日期:1999-01-01 00:00:00
abstract::Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use. Sulfasalazin...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199106030-00005
更新日期:1991-05-01 00:00:00
abstract::Anaemia is common in patients with haematological malignancy, occurring in the majority of patients with malignant disease who are treated with chemotherapy. Most patients will have their anaemia attributed to the cytokine-mediated anaemia of chronic disease. Many of these patients with anaemia will be symptomatic wit...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200225070-00006
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. OBJECTIVE:The aim of the study was to characterize ADRs reported to the WHO-ADR database, ...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/BF03262002
更新日期:2012-12-01 00:00:00
abstract::Drug-induced torsade de pointes is a rare life-threatening adverse drug reaction (ADR) which is strongly influenced by gender. Drugs that prolong cardiac repolarisation include antiarrhythmics, gastrokinetics, antipsychotics, antihistamines and antibacterials. Such drugs share the potential to block cardiac voltage-ga...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200124080-00002
更新日期:2001-01-01 00:00:00
abstract::Similar to other beta-lactam antibacterials, carbapenems have a neurotoxic potential that seems to be higher than that of the penicillins and cephalosporins. Seizures have been reported in several large studies of patients treated with imipenem/cilastatin. However, it seems clear that the main factor increasing the ri...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199615020-00001
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND:The roll out of various public health programmes involving mass administration of medicines calls for the deployment of responsive pharmacovigilance systems to permit identification of signals of rare or even common adverse reactions. In developing countries in Africa, these systems are mostly absent and the...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-200831100-00005
更新日期:2008-01-01 00:00:00
abstract::In the original publication of the article, the trend line for non-EEA cases in figure 4 is incorrect. In this correction, the original Fig. 4 (Fig. 1) and the correct Fig. 4 (Fig. 2) are published. ...
journal_title:Drug safety
pub_type: 杂志文章,已发布勘误
doi:10.1007/s40264-018-0700-0
更新日期:2018-12-01 00:00:00
abstract::The complications of failure, neural injury and local anaesthetic toxicity are common to all regional anaesthesia techniques, and individual techniques are associated with specific complications. All potential candidates for regional anaesthesia should be thoroughly evaluated and informed of potential complications. I...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200124060-00002
更新日期:2001-01-01 00:00:00
abstract::The most frequently reported symptoms in heart failure are fatigue and dyspnoea, which limit exercise tolerance. However, several surveys reveal other changes in physical and psychological well-being which affect the patient's perception of 'quality of life'. The introduction of new treatments for heart failure has st...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199106040-00002
更新日期:1991-07-01 00:00:00
abstract::It has been more than 25 years since an adverse drug reaction (ADR) monitoring agency was first established in China. In the past few years, the National ADR Monitoring System (NADRMS) has developed rapidly in the country. However, this system has not been reviewed in detail in the literature. Our aim was to demonstra...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.1007/s40264-016-0446-5
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:The epidemiology of naturally occurring intussusception is known to increase significantly between the ages of 3 and 8 months. Post-licensure studies have reported a fivefold and twofold increase in intussusception in the first week after the first dose and second dose, respectively, of current rotavirus v...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-016-0424-y
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Researchers using observational data to understand drug effects must make a number of analytic design choices that suit the characteristics of the data and the subject of the study. Review of the published literature suggests that there is a lack of consistency even when addressing the same research question...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-013-0103-1
更新日期:2013-10-01 00:00:00
abstract::A number of affluent countries are moving to eliminate thiomersal (thimerosal), an ethylmercury preservative, from vaccines as a precautionary measure because of concerns about the potential adverse effects of mercury in infants. The WHO advocates continued use of thiomersal-containing vaccines in developing countries...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200528020-00001
更新日期:2005-01-01 00:00:00
abstract::While classifications into generations according to antimicrobial activity has helped clinicians incorporate the increasing number of cephalosporins into their pharmacological repertoire, adverse effects among the different agents fail to follow similar categories. In general, cephalosporins are fairly well tolerated ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199309020-00005
更新日期:1993-08-01 00:00:00
abstract::Postoperative nausea and vomiting (PONV) is an age-old problem; more so since the blooming of ambulatory or day surgery centres within the last 2 decades. The aetiology of PONV is multifactorial. The incidence of PONV is usually higher in women and children than in men. PONV not only causes patient discomfort, anxiety...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199614030-00005
更新日期:1996-03-01 00:00:00