Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotropin-releasing hormone (GnRH) agonists are the mainstay of treatment for recurrent and metastatic prostate cancer. GnRH agonists are also an important part of therapy for many men with localized or locally advanced prostate cancer. Although GnRH agonists improve survival in certain settings, they involve adverse effects including vasomotor flushing, obesity, and osteoporosis. This article describes the evidence that GnRH agonists increase risk for diabetes and cardiovascular disease and reviews the potential mechanisms for treatment-related morbidity.
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PMID:Androgen deprivation therapy and risk for diabetes and cardiovascular disease in prostate cancer survivors. 1876 13

Niacin has long been used in the treatment of dyslipidemia and cardiovascular disease. Recent research on niacin has been focused on understanding the mechanism of action of niacin and preparation of safer niacin formulations. New findings indicate that niacin does the following: 1) it inhibits hepatic diacylglycerol acyltransferase 2, resulting in inhibition of triglyceride synthesis and decreased apolipoprotein B-containing lipoproteins; 2) it decreases the surface expression of hepatic adenosine triphosphate synthase beta-chain, leading to decreased holoparticle high-density lipoprotein catabolism and increased high-density lipoprotein levels; and 3) it increases redox potential in arterial endothelial cells, resulting in inhibition of redox-sensitive genes. Flushing, an adverse effect of niacin, results from niacin receptor GPR109A-mediated production of prostaglandin D2 and E2 via DP1 and EP2/4 receptors. DP1 receptor antagonist (laropiprant) attenuates the niacin flush. A reformulated preparation of extended-release niacin (Niaspan; Abbott, Abbott Park, IL) lowers flushing compared with an older Niaspan formulation. These advancements in niacin research have rejuvenated its use for the treatment of dyslipidemia and cardiovascular disease.
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PMID:Niacin: an old drug rejuvenated. 1908 Jul 27

There are many factors that increase the risk of cardiovascular disease, and a prominent factor among these is dyslipidemia. The following literature review focuses on the use of niacin therapy in order to treat dyslipidemia and how to control the associated "niacin flush." The associated studies gathered are reviews and randomized control trials. They were obtained by using electronic searches. Certain keywords took precedence, and articles focusing on niacin therapy were chosen. Recent research has found promising insight into more effective prevention of the niacin-mediated flush through a selective antagonist for the prostaglandin D2 receptor, laropiprant. Aspirin (or NSAIDs) also provide some prevention for flushing, although recent studies have shown that it is not as effective as laropiprant. There is a need for further research in order to come to a clear conclusion regarding combined therapies of aspirin and laropiprant pretreatment, as well as exact dosage requirements.
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PMID:Mechanisms of flushing due to niacin and abolition of these effects. 1987 84

Statin therapy is widely used in treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is not associated with significant increase in high-density lipoprotein cholesterol (HDL-c) or significant decrease in triglyceride level. Importantly, emerging evidence has suggested that low HDL-c and high triglyceride are strong risk factors associated with CVD. Niacin is a unique lipid-lowering medication with a capacity to lower low-density lipoprotein cholesterol (LDL-c), triglyceride and increase HDL-c. In this context, there is considerable interest in trials involving niacin as monotherapy and in association with statins. Recent trials showed that the combination of statin and niacin is an effective treatment not only for dyslipidaemia (high LDL-c, high triglyceride and low HDL-c) but also for carotid intima-media thickness, one of the important features of atherosclerosis. Furthermore, niacin is distinguished by its unique capacity to effectively lower lipoprotein (a) [Lp(a)] levels. Flushing is the only factor that limits the wide use of niacin. The combination of statin and niacin has potential as a future treatment of atherogenic dyslipidemias; however, further evidence is needed. Importantly, the impact of niacin and statin on insulin sensitivity is not yet known. This article projects the potential benefits of current and possible future niacin clinical trials.
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PMID:What does the future hold for niacin as a treatment for hyperlipidaemia and cardiovascular disease? 2068 17

Recently two studies on the effect of addition of extended-release niacin to statin treatment on measures of carotid atherosclerosis were estimated in the ARBITER 6-HALTS study (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies) study and the Oxford Niacin Study were published. Adding niacin to statin treatment significantly diminished carotid atherosclerosis as measured by ultrasound carotid intima-media thickness or magnetic resonance imaging. An inhibitor of niacin induced flushing, laropiprant has been developed and demonstrated to considerably improve the tolerability of niacin therapy without impeding on its effect on lipoproteins. Still however clear evidence for the clinical benefit of long-term niacin treatment on cardiovascular morbidity and mortality is lacking. The development situation for ezetimibe is similar to that of niacin. Long-term interventional studies with hard endpoints of both therapies are ongoing. Also both drugs, when proven efficient and safe, are eagerly needed in the prevention of cardiovascular disease.
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PMID:HDL and LDL as therapeutic targets for cardiovascular disease prevention: the possible role of niacin. 2073 53

Advances in clinical lipidology during the last 18 months include the establishment of high-sensitivity C-reactive protein (hsCRP) as an important risk marker for cardiovascular disease. Determining hsCRP levels should help the clinician single out patients at particularly high risk. However, more research needs to be done in this area. Furthermore, statins do not seem to be of benefit in patients with severe congestive heart failure, on chronic hemodialysis, or with aortic stenosis. Next, plasma triglyceride levels are now considered an important risk marker for cardiovascular disease, but the therapeutic benefits related to lowering triglyceride levels remain difficult to achieve. Also, nicotinic acid has gained more interest partly because recent studies have demonstrated positive effects on atherosclerosis development and partly because the side effect of flushing seems to be partially avoidable with the concomitant administration of laropiprant. Both the raising of high-density lipoprotein cholesterol by nicotinic acid and the additional lowering of low-density lipoprotein cholesterol by ezetimibe and eprotirome will need to demonstrate hard endpoint reductions in large-scale intervention trials. Trials of niacin/laropiprant (the AIM-HIGH and HPS2-THRIVE studies) and ezetimibe (the IMPROVE-IT study) are already under way.
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PMID:Recent advances in preventing cardiovascular disorders by managing lipid levels. 2117 59

Hot flushes are complained of by approximately 75% of all postmenopausal women, and hormone therapy (HT) is the most effective way to alleviate them. Hot flushes are characterized by altered vascular function and sympathetic nervous system activity. Hot flushes occurred more often in women attending large, non-randomized observational studies (e.g. Nurses' Health Study), where HT use protected against cardiovascular disease (CVD). However, they were absent (or mild) in randomized HT trials where HT use was accompanied with an elevated risk for CVD. Hot flushes, if a factor for cardiovascular health, could partly explain the conflict between observational and randomized trials. Several cross-sectional studies imply that hot flushes are detrimental to the cardiovascular system. However, the data are not uniform, and hot flushes were recalled retrospectively or during HT use. In our prospective study hot flushes were accompanied with a vasodilatory effect during endothelial testing, and this was related to the severity of hot flushes. Night-time hot flushes were followed with transient rises in ambulatory blood pressure (BP). However, no effect of hot flushes on diurnal BP was detected. The use of estradiol showed no harmful effects on endothelial function in women with hot flushes, but in non-flushing women oral, but not transdermal, estradiol led to vasoconstrictive changes. Estradiol complemented with medroxyprogesterone acetate eliminated the vasoconstrictive effect of sole oral estradiol. Thus, both oral and transdermal estradiol are applicable in flushing women, whereas a transdermal route should be favored in non-flushing women if used e.g. for bone protection.
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PMID:Menopausal hot flushes and vascular health. 2125 7

Abnormal blood lipids are the major modifiable risk factor underlying the development of cardiovascular disease. Niacin has a profound ability to reduce low-density lipoprotein-C, very low-density lipoprotein-C and triglycerides and is the most effective pharmacological agent to increase high-density lipoprotein-C. Recently, the receptor for niacin, GPR109A, was discovered. GPR109A in the adipocyte mediates a niacin-induced inhibition of lipolysis, which could play a crucial part in its role as a lipid-modifying drug. GPR109A in epidermal Langerhans cells mediates flushing, an unwanted side effect of niacin therapy. For the past decade, the functions of GPR109A have been studied and full or partial agonists have been developed in an attempt to achieve the beneficial effects of niacin while avoiding the unwanted flushing side effect. This review presents what is known to date about GPR109A biology and function and the future of GPR109A as a pharmacological target.
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PMID:Future of GPR109A agonists in the treatment of dyslipidaemia. 2141

Niacin is a water-soluble B vitamin (B3) known to have favorable effects on multiple lipid parameters, including raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglycerides (TGs), lipoprotein(a), and low-density lipoprotein cholesterol (LDL-C). Although LDL-C remains the primary target of lipid-altering therapy, current guidelines emphasize HDL-C and other modifiable lipid factors as key secondary targets. Thus, niacin is considered an important therapeutic option to help reduce the risk of cardiovascular disease in patients with mixed dyslipidemia who, in addition to high LDL-C, have elevated TGs and low HDL-C. Although available prescription niacin products, including immediate-release niacin (IR; Niacor) and an extended-release niacin formulation (Niaspan), have demonstrated safety and efficacy in randomized clinical trials, confusion remains among health care providers and their patients regarding the various commercially available nonprescription dietary supplement niacin products. These dietary supplements, which include IR, sustained-release (SR), and "no-flush" or "flush-free" niacin products, are not subject to the same stringent US Food and Drug Administration regulations as prescription drugs. In fact, both the American Heart Association and the American Pharmacists Association recommend against the use of dietary supplement niacin as a substitute for prescription niacin. Although some dietary supplement IR and SR niacin products have demonstrated a lipid response in clinical trials, products labeled as "no-flush" or "flush-free" that are intended to avoid the common niacin-associated adverse effect of flushing generally contain minimal or no free, pharmacologically active niacin and therefore lack beneficial lipid-modifying effects. To clarify important differences between available prescription and dietary supplement niacin products, this article contrasts current regulatory standards for dietary supplements and prescription drugs and provides an overview of available clinical data from key trials of niacin.
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PMID:Important considerations for treatment with dietary supplement versus prescription niacin products. 2147 95

Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin's uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D(2) receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin-laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin's position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences.
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PMID:Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia. 2170 18


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