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)

Niacin (nicotinic acid and nicotinamide) is a vitamin used as a source of the NAD+ and NADP+ coenzymes required for many metabolic processes. Its low dietary levels induce the development of pellagra. Niacin has been used for decades in the treatment of patients with disturbed lipid and lipoprotein metabolism, this being the main cause of atherosclerotic changes in cardiovascular diseases. It is still the most efficacious drug in terms of its ability to increase HDL cholesterol content accompanied by a decrease in all atherogenic lipoproteins (VLDL, LDL, and L(a)) as well as fatty acids and triglycerides. Niacin also increases adiponectin level, which might result in additional atheroprotection. There are studies confirming the beneficial action of niacin against migraine and hyperphosphatemia associated with renal failure, ethanol-induced neurodegeneration, and loss of beta-cell function in type 1 diabetes. Moreover, it augments plasma tryptophan concentrations in HIV-infected patients and thyroid radiosensitivity to 131I. Inhibition of the invasion of hepatoma cells has also been proven. However, it is necessary to point out that the currently applied niacin preparations might exhibit such side effects as cutaneous flushing, gastrointestinal disturbances, and hepatotoxicity, particularly during treatment with sustained-release niacin preparations. The recent discovery of the G-protein-coupled receptor GPR109A, which mediates the antilipolytic effects induced by nicotinic acid in adipocytes as well as cutaneous vasodilation, allows the development of new agents interacting with this receptor. In view of these observations, niacin therapy must be accompanied by control of the choice of niacin preparation and its dose in order to eliminate or at least limit its side effects.
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PMID:[Niacin in therapy]. 1755 32

Hyperphosphatemia is an important modifiable risk factor in the dialysis population because it is linked to increased mortality. Existing phosphate-reducing agents either increase the risk of vascular calcification or are costly with high pill burden. Niacin shows promise as a cheap drug with low pill burden and a novel mode of action. Niacin and its metabolite nicotinamide inhibit the small intestinal sodium-phosphate cotransporter. Approximately 50% of intestinal phosphate absorption occurs through this route under physiological conditions. Studies performed on the dialysis population with niacin and nicotinamide have shown significant phosphate reduction with lowering of the calcium-phosphorus product. The well documented increase in serum HDL levels may also offer survival benefits. Side-effects include flushing, which is controlled with aspirin, diarrhea, and thrombocytopenia, which may be treatment-limiting. Niacin is cheap and phosphate reduction can be achieved by administration of one or two tablets per day. These factors will boost compliance in developing countries. Further basic research and large-scale clinical trials are needed in this field.
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PMID:Niacin and analogs for phosphate control in dialysis--perspective from a developing country. 1903 39

Niacin has profound and unique effects on lipid metabolism. In addition to increasing high-density lipoprotein cholesterol, it is also known to decrease total cholesterol, low-density lipoprotein cholesterol, and triglyceride. Interestingly, the plasma concentration of lipoprotein(a) [Lp(a)], which has been suggested to play a role as an independent risk factor for coronary heart disease, is also decreased by niacin. Therefore, it is not surprising that in the literature it was given unique description as broad-spectrum lipid drug. Its impact is referred to as desirable normalization of a range of cardiovascular risk factors. However, its clinical use is limited due to harmless but unpleasant unique side effect of cutaneous flushing. Interestingly, recent experimental and clinical studies suggest the potential benefit of niacin as a treatment of dyslipidemia and high plasma phosphate associated with chronic kidney disease (CKD). Both dyslipidemia and high serum phosphate levels are shown to be associated with higher cardiovascular mortality. Furthermore, niacin administration improves renal tissue lipid metabolism, renal function and structure, hypertension, proteinuria, and histological tubulointerstitial injury. Further studies are required before the use of niacin for the treatment of both dyslipidemia and hyperphosphatemia with CKD advocated.
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PMID:Niacin as potential treatment for dyslipidemia and hyperphosphatemia associated with chronic renal failure: the need for clinical trials. 2048 51

Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia.
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PMID:Recurrent acute kidney injury associated with metastatic bronchial carcinoid. 2200 80

Nearly all patients with end-stage renal disease develop hyperphosphatemia. These patients typically require oral phosphate binders for life-long phosphorus management, in addition to dietary restrictions and maintenance dialysis. Recently, niacin, a traditional antilipemic agent, drew attention as an experimental treatment for hyperphosphatemia. The purpose of this article was to report on new findings regarding niacin's novel effects and to review the possibility of repurposing niacin for hyperphosphatemia treatment in dialysis patients by elucidating its safety and efficacy profiles along with its synergistic clinical benefits. Following approval from the Institutional Review Board, we tracked the yearly trends of order frequency of niacin in comparison with statins and sevelamer in a tertiary care hospital. Also, a Cochrane Library and PubMed literature search was performed to capture prospective clinical trials on niacin's hypophosphatemic effects in dialysis patients. Niacin use in clinical settings has been on the wane, and the major contribution to that originates from the wide use of statins. Niacin use rates have further plummeted following a trial failure which prompted the suspension of the niacin-laropiprant (a flushing blocker) combination product in the global market. Our literature search identified ten relevant articles. Overall, all studies demonstrated that niacin or nicotinamide (the metabolite form) reduced serum phosphorus levels as well as Ca-P products significantly. Additive beneficial effects on lipid parameters were also observed. Sevelamer appeared superior to niacin in a comparative study, but the study design had several limitations. The intervention dosage for niacin ranged from 375 to 1,500 mg/day, with the average daily dose of approximately 1,000-1,500 mg. Niacin can be a patient-convenient and inexpensive alternative or adjunctive therapy for phosphorus management in dialysis patients. Further well-designed, large-scale, long-term, comparative trials are needed to successfully repurpose niacin for the new indication.
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PMID:Niacin as a drug repositioning candidate for hyperphosphatemia management in dialysis patients. 2534 8