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)

Optical coherence tomography (OCT) is a fiber-optic technology that enables high-resolution intracoronary imaging. The aim of this study was to evaluate the safety and feasibility of intracoronary imaging with OCT in the clinical setting; 76 patients with coronary artery disease from 8 centers were enrolled. The OCT imaging system (ImageWire, Light Imaging Inc., Westford, Massachusetts) consists of a 0.006 inch fiber-optic core that rotates within a 0.016 inch transparent sheath. OCT imaging was performed during occlusion of the artery with a compliant balloon and continuous flushing. Intravascular ultrasound (IVUS) imaging was performed in the same segments. We assessed the safety and feasibility of the OCT imaging, compared with IVUS. Vessel occlusion time was 48.3 +/- 13.5 seconds and occlusion-balloon pressure was 0.4 +/- 0.1 atmospheres. Flushing with lactated Ringer's solution was performed at a rate of 0.6 +/- 0.4 ml/s. No significant adverse events, including vessel dissection or fatal arrhythmia, were observed. Procedural success rates were 97.3% by OCT and 94.5% by IVUS. The OCT image wire was able to cross 5 of 6 tight lesions that the IVUS catheter was unable to cross. Of the 98 lesions in which both OCT and IVUS were successfully performed, OCT imaging had an advantage over IVUS for visualization of the lumen border. Minimum lumen diameter and area measurements were significantly correlated between OCT and IVUS imaging (r = 0.91, p <0.0001 and r = 0.95, p <0.0001, respectively). In conclusion, this multicenter study demonstrates the safety and feasibility of OCT imaging in the clinical setting.
Am J Cardiol 2008 Mar 01
PMID:Safety and feasibility of an intravascular optical coherence tomography image wire system in the clinical setting. 1830 99

Niacin (nicotinic acid) is not optimally used mainly because of flushing, a process mediated primarily by prostaglandin D(2), which leads to poor patient compliance and suboptimal dosing. This phase II dose-ranging study was designed to assess whether the prostaglandin D(2) receptor 1 antagonist laropiprant (LRPT; MK-0524) would (1) reduce extended-release niacin (ERN)-induced flushing in dyslipidemic patients and (2) support a novel accelerated ERN dosing paradigm: initiating ERN at 1 g and advancing rapidly to 2 g. In part A of the study, 154 dyslipidemic patients were randomized to LRPT 150 mg/day or placebo in a 9-week, 2-period crossover study. Patients who completed part A (n = 122) entered part B (after a 2-week washout), together with additional patients who entered part B directly (n = 290). Part B patients were randomized to placebo, ERN 1 g (Niaspan, no previous titration), or ERN 1 g coadministered with LRPT 18.75, 37.5, 75, or 150 mg for 4 weeks, with doubling of the respective doses for the remaining 4 weeks. Patients treated with LRPT plus ERN experienced significantly less ERN-induced flushing than those treated with ERN alone during the initiation of treatment (ERN 1 g, week 1) and the maintenance treatment (ERN 1 to 2 g, weeks 2 to 8). All doses of LRPT were maximally effective in inhibiting niacin-induced flushing. LRPT did not alter the beneficial lipid effects of ERN. LRPT plus ERN was well tolerated. In conclusion, the significant reduction in ERN-induced flushing provided by LRPT plus ERN supports an accelerated ERN dose-advancement paradigm to achieve rapidly a 2-g dose in dyslipidemic patients.
Am J Cardiol 2008 Mar 01
PMID:Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. 1830 10

Niacin, or nicotinic acid, has established efficacy for the treatment of dyslipidemia, but the clinical use of niacin has been limited by cutaneous flushing, a well-recognized associated adverse effect. Flushing has been cited as the major reason for the discontinuation of niacin therapy, estimated at rates as high as 25%-40%. A number of studies have established that moderate doses of prostaglandin inhibitors reduce the cutaneous flushing response from niacin administration. Other strategies for reducing flushing include regular consistent dosing, the use of extended-release formulations, patient education, dosing with meals or at bedtime, and the avoidance of alcohol, hot beverages, spicy foods, and hot baths or showers close to or after dosing. Because niacin has recognized cardiovascular benefits, promoting patient awareness of factors that can minimize niacin-induced flushing can help enhance the tolerability of this valuable dyslipidemic agent.
Am J Cardiol 2008 Apr 17
PMID:Niacin use and cutaneous flushing: mechanisms and strategies for prevention. 1837 36

Nicotinic acid (niacin) has long been used for the treatment of lipid disorders and cardiovascular disease. Niacin favorably affects apolipoprotein (apo) B-containing lipoproteins (eg, very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], lipoprotein[a]) and increases apo A-I-containing lipoproteins (high-density lipoprotein [HDL]). Recently, new discoveries have enlarged our understanding of the mechanism of action of niacin and challenged older concepts. There are new data on (1) how niacin affects triglycerides (TGs) and apo B-containing lipoprotein metabolism in the liver, (2) how it affects apo A-I and HDL metabolism, (3) how it affects vascular anti-inflammatory events, (4) a specific niacin receptor in adipocytes and immune cells, (5) how niacin causes flushing, and (6) the characterization of a niacin transport system in liver and intestinal cells. New findings indicate that niacin directly and noncompetitively inhibits hepatocyte diacylglycerol acyltransferase-2, a key enzyme for TG synthesis. The inhibition of TG synthesis by niacin results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles. Previous kinetic studies in humans and recent in vitro cell culture findings indicate that niacin retards mainly the hepatic catabolism of apo A-I (vs apo A-II) but not scavenger receptor BI-mediated cholesterol esters. Decreased HDL-apo A-I catabolism by niacin explains the increases in HDL half-life and concentrations of lipoprotein A-I HDL subfractions, which augment reverse cholesterol transport. Initial data suggest that niacin, by inhibiting the hepatocyte surface expression of beta-chain adenosine triphosphate synthase (a recently reported HDL-apo A-I holoparticle receptor), inhibits the removal of HDL-apo A-I. Recent studies indicate that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes, key cytokines involved in atherosclerosis. The niacin flush results from the stimulation of prostaglandins D(2) and E(2) by subcutaneous Langerhans cells via the G protein-coupled receptor 109A niacin receptor. Although decreased free fatty acid mobilization from adipose tissue via the G protein-coupled receptor 109A niacin receptor has been a widely suggested mechanism of niacin to decrease TGs, physiologically and clinically, this pathway may be only a minor factor in explaining the lipid effects of niacin.
Am J Cardiol 2008 Apr 17
PMID:Mechanism of action of niacin. 1837 37

Niacin is the most potent lipid-altering agent for raising high-density lipoprotein (HDL) cholesterol levels. Niacin also lowers triglyceride (TG) levels, lowers low-density lipoprotein (LDL) cholesterol levels, and improves lipoprotein particle size and subclass distribution. Niacin's major adverse experience (AE) is flushing. Niacin may also increase glucose levels, liver enzymes, and uric acid levels and cause other AEs that may have clinical relevance in selected patients. Simvastatin is representative of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) class of lipid-altering drugs, which are the most effective agents for lowering LDL cholesterol levels and also have modest benefits in raising HDL cholesterol and lowering TG levels. The most common AEs with statins are muscle AEs and modest liver enzyme elevations. Because niacin and statins have complementary lipid effects and because individually, niacin and statins have been shown in outcomes studies to reduce atherosclerotic coronary artery disease events, the combined use of these 2 agents has significant potential to not only improve the lipid values of patients but improve their lives as well. Equally important is ensuring that the combination of niacin and simvastatin has an acceptable safety profile, with no greater AEs than would otherwise be expected by adding 1 agent to the other.
Am J Cardiol 2008 Apr 17
PMID:Safety of niacin and simvastatin combination therapy. 1837 39

The efficacy and safety of 2 regimens of a combination of a proprietary niacin extended release plus simvastatin (NER/S; 1,000/20 and 2,000/20 mg/day) were compared with simvastatin monotherapy (20 mg/day) for 24 weeks in 319 high-risk patients with predominantly mixed dyslipidemia who were already at National Cholesterol Education Program Adult Treatment Panel III risk-adjusted goals for low-density lipoprotein cholesterol. After a run-in on simvastatin 20 mg/day, both NER/S doses (1,000/20 and 2,000/20 mg/day) resulted in greater decreases in non-high-density lipoprotein (HDL) cholesterol vs simvastatin 20 mg/day (-13.9% and -22.5% vs -7.4%, respectively; p <0.01). Significant improvements in HDL cholesterol, triglycerides, apolipoprotein B, lipoprotein(a), and total/HDL cholesterol ratio were also observed. Patients with hypertriglyceridemia (triglycerides > or =200 mg/dl) typically had greater lipid responses to NER/S with the notable exception that HDL cholesterol responses to NER/S were similar in those with or without increased triglycerides. Treatment with both doses of NER/S was well tolerated; < or =60% of patients in any treatment group experienced flushing, >90% of flushing was mild or moderate in intensity, and only 7.5% of patients in both NER/S treatment groups discontinued because of flushing. The safety of NER/S was consistent with the safety profile of each individual component. In conclusion, this study showed that NER/S provided additional clinically relevant improvements in multiple lipid parameters and was safe and well tolerated.
Am J Cardiol 2008 May 15
PMID:Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study). 1847 54

Treatment with niacin effectively improves multiple lipid parameters and cardiovascular outcomes. Widespread use of niacin, however, is limited by flushing, which is mediated primarily by prostaglandin D2 (PGD2). Laropiprant is a selective PGD2 receptor 1 (DP1) antagonist that reduces objective measures of niacin-induced flushing symptoms upon initiation of therapy and with more chronic use. Results from early dosing and formulation studies have culminated in the development of a combination extended-release (ER) niacin/laropiprant tablet aimed at providing the beneficial lipid-modifying effects of niacin, while reducing niacin-induced flushing. The improvement in the tolerability of niacin with ER niacin/laropiprant allows niacin dosing to initiate directly at 1 g and rapidly advance to a 2-g target dose. ER niacin/laropiprant generally is tolerated well and represents a new treatment option for dyslipidemia that offers the potential for more patients to receive the lipid-modifying and cardiovascular benefits of niacin.
Cardiol Clin 2008 Nov
PMID:Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors. 1903 52

Ibn Sina, known as Avicenna in the West, was a celebrated Persian thinker, philosopher, and physician who is remembered for his masterpiece, The Canon of Medicine. The Canon that served as an essential medical encyclopedia for scholars in the Islamic territories and Europe for almost a millennium consisted of 5 books. In the third book, Avicenna described patients with symptoms of carotid hypersensitivity syndrome. These patients, who had excessive yawning, fatigue, and flushing, dropped following pressure on their carotids. Based on such history, it seems that Avicenna was the first to note the carotid sinus hypersensitivity, which presents with vasovagal syncope following compression of the carotid artery. In this paper, we presented a brief account of Avicenna's life and works and discuss his description of the so-called carotid hypersensitivity syncope. Notwithstanding his loyalty to the Greek theory of humoralism, Avicenna set forth his own version of "theory of spirits" to explain the mechanism of this disease. An account of the theory of spirits is also given.
Int J Cardiol 2009 May 29
PMID:Vasovagal syncope in the Canon of Avicenna: the first mention of carotid artery hypersensitivity. 2109 29

In a 56-year-old lady, a carcinoid tumor of the terminal ileum metastasized to regional lymph nodes, and the liver was removed by hemicolectomy in 2002. Following a history of cutaneous flushing, diarrhea, and bronchoconstriction 3 years later, a somatostatin therapy was instituted. As flushing and diarrhea resolved and levels of urinary excretion of 5-hydoxyindoleacetic acid decreased, shortness of breath was progressive and prompted a cardiac exam. Despite poor resolution, echocardiography revealed a thickening of the tricuspid valves (TK) with reduced mobility along with right atrial (RA) and right ventricular (RV) dilatation. The pulmonary valve was unobtrusive. Magnetic resonance (MR) imaging revealed extensive fibrous tissue extending from the valvular base to the tip of the tricuspid leaflets. Retraction and immobilization of the TK caused a mild stenosis and a large regurgitant flow. Because medical treatment of tricuspid regurgitation was ineffective, the TK was excised and a Hancock 25-mm bioprosthetic valve was implanted. The postoperative course was uncomplicated, and the patient recuperated and resumed normal daily activities.
Clin Cardiol 2009 Jun
PMID:Magnetic resonance imaging of carcinoid heart disease. 1938 78

Niacin has beneficial effects on a patient's lipid and lipoprotein profiles and cardiovascular risk, particularly at doses >2 g/day, but is underused due to flushing. Laropiprant (LRPT), a selective prostaglandin D(2) receptor-1 antagonist, decreases flushing associated with extended-release niacin (ERN). We compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of Kos Life Sciences LLC). Patients with dyslipidemia (n = 1,455) were randomized 1:1 to ERN/LRPT (1 g for 4 weeks advanced to 2 g for 12 weeks) or N-ER (0.5 g for 4 weeks titrated in 0.5-g increments every 4 weeks to 2 g for the final 4 weeks). Aspirin/nonsteroidal anti-inflammatory drugs were allowed to mitigate flushing. Flushing severity was assessed using the validated Global Flushing Severity Score (GFSS; none 0, mild 1 to 3, moderate 4 to 6, severe 7 to 9, extreme 10). Patients on ERN/LRPT, despite more rapid niacin titration, had less flushing than those on N-ER, as measured by number of days per week with moderate or greater GFSS across the treatment period (p <0.001). More than 2 times as many patients had no episodes of moderate, severe, or extreme flushing (GFSS > or =4) with ERN/LRPT than with N-ER (47.0% vs 22.0%, respectively) across the treatment period. Fewer patients on ERN/LRPT discontinued due to flushing than those on N-ER (7.4% vs 12.4%, p = 0.002). Other than the decrease in flushing, the safety and tolerability profile of ERN/LRPT was similar to that of N-ER. In conclusion, improvement in flushing with ERN/LRPT versus gradually titrated N-ER supports a rapidly advanced 1-g --> 2-g dosing regimen, allowing patients to start at 1 g and quickly reach and tolerate the optimal 2 g dose of ERN.
Am J Cardiol 2009 Jul 01
PMID:Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. 1957 24


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