Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotinic acid (CAS 59-67-6) is the only hypolipidemic agent whose activity has been shown both on atherosclerotic lesions and on long term mortality. Unfortunately, its use is hindered by the frequent occurrence ( > 70%) of adverse reactions (i.e. cutaneous rash, pruritus and, most significantly, flush). New prodrugs of nicotinic acid have been prepared by the use of diacylglycerol esters. In the rat, after acute oral administration of these products, a significant decrease of the free fatty acid plasma levels was obtained without the dramatic increase in nicotinic acid plasma levels observed after the oral administration of an equimolecular dose of nicotinic acid. The most interesting ester, S 16961 ((d,l)-1,2-dipalmitoyl-3-nicotinoyl glycerol, CAS 160555-46-4) is undergoing clinical trials.
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PMID:Synthesis of 1,2-diacyl-3-nicotinoyl glycerol derivatives and evaluation of their acute effects on plasma lipids in the rat. 748 22

Nicotinic acid and derivatives are effective in numerous forms of hyperlipoproteinemia. Its primary mode of action is to inhibit lipolysis in adipose tissue and to prevent the utilization of free fatty acids for TG-rich lipoprotein synthesis in the liver. Consequently, it decreases the plasma lipoproteins which are considered to be atherogenic--VLDL, LDL and Lp(a), while it increases the antiatherogenic lipoprotein--HDL. A gradual administration of nicotinic acid or derivatives is useful to reduce the side effects such as flushing and itching. In the secondary prevention trials, nicotinic acid therapy with other hypolipidemic drugs asserted protective effects on the development/progression of cardiovascular disease.
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PMID:[Nicotinic acid and derivatives for therapy of hyperlipoproteinemia]. 785 25

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.
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PMID:Currently available hypolipidaemic drugs and future therapeutic developments. 859 27

Niacin is a useful lipid-modifying drug because it (1) decreases low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and lipoprotein(a), and (2) raises high-density lipoprotein (HDL) cholesterol. Its use tends to be limited by side effects and inconvenient dosing regimens. The availability of an extended-release preparation (Niaspan-which has safety and efficacy similar to immediate-release niacin but which can be given once a day) provides an opportunity to increase the use of this effective lipid-modifying agent. To study the safety and efficacy of escalating doses of extended-release niacin, hyperlipidemic patients were randomly assigned to placebo or Niaspan. A forced dose-titration was done with the dosage increasing by 500 mg every 4 weeks to a maximum of 3,000 mg/day. Niaspan showed dose-related changes in total, LDL, and HDL cholesterol levels, triglycerides, cholesterol/HDL ratio, and lipoprotein(a). At a dosage of 2,000 mg/day, total cholesterol decreased by 12.1%, LDL cholesterol by 16.7%, triglycerides by 34.5%, and lipoprotein(a) by 23.6%; HDL cholesterol increased by 25.8%. Flushing was the most commonly reported side effect; flushing episodes tended to decrease with time despite an increasing dose of niacin. Of the reported side effects, only pruritus and rash were significantly different between the 2 groups. Aspartate aminotransferase, lactate dehydrogenase, and uric acid increased in a dose-dependent fashion, but fasting blood sugar increased by about 5% across most dosages. Two subjects had aspartate aminotransferase levels greater than twice the upper limit of normal, but there were no subjects in whom transaminases increased to 3 times the upper limit of normal. Women tended to have a greater LDL cholesterol response to the medication and also experienced more side effects, especially at higher dosages. Thus, the use of lower dosages of niacin may be desirable in women. The results of this dose-escalation study show beneficial effects of Niaspan on the entire lipid profile. At the maximum recommended dosage of 2,000 mg/day, all lipid and lipoprotein levels changed in desirable directions. Side effects (other than flushing) and blood chemistries were comparable to those seen with immediate-release niacin.
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PMID:Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. 991 61

Pellagra is a systemic disturbance caused by a cellular deficiency of niacin, resulting from inadequate dietary nicotinic acid and/or its precursors, the essential amino-acid tryptophan. In Europe and North America cases of pellagra are rarely encountered, but in some developing countries this disease is frequent, and is the most frequent clinical feature of nutritional deficiency of adult. The principal causes of pellagra are: nutritional niacin deficiency; chronic alcoholism; gastro-intestinal malabsorption; some medications (5-fluoro-uracil, isoniazid, pyrazinamide ehtionamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol). The diagnosis of pellagra is based on the patient's history and the presence of "3 D syndrome": dermatitis, diarrhea, and dementia. The dermatitis caused by pellagra is a bilaterally symmetrical erythema at the sites of solar exposure. The dermatitis begins in the form of an erythema with acute or intermittent onset gradually changing to an exsudative eruption on the dorsa of the hand, face, neck, and chest with pruritus and burning. Acute dermatitis of pellagra resembles sunburn in the first stages, sometimes with vesicles and bullae. The gastro-intestinal disturbances are: anorexia, nausea, epigastric discomfort and chronic or recurrent diarrhea. Anorexia and malabsorbative diarrhea lead to a state of malnutrition and cachexia. Stools are typically watery, but occasionally can be bloody and mucoid. Neuropsychologic manifestation included photophobia, asthenia, depression, hallucinations, confusions, memory loss and psychosis. As pellagra advances, patient become disoriented, confused and delirious; then stuporous and finally die. Pathological changes in the skin is non-specific, there are no chemical tests available to definitively diagnose pellagra. However low levels of urinary excretion of N-methylnicotinamide and pyridone indicates niacin deficiency. The treatment of pellagra consisted to exogenous administration of niacin or nicotinamide cures. Topical management of skin lesions with emollients may reduce discomfort. The therapy should also include other B vitamins, zinc and magnesium as well as a diet rich in calories. The prevention is based in the nutritional education (food sources of niacin: eggs, bran, peanuts, meat, poultry, fish, red meat, legumes and seeds), and the eviction of alcohol.
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PMID:[Pellagra]. 1620 85

In addition to its use as a nutritional supplement, niacin (nicotinic acid or vitamin B3) is medically prescribed to treat hyperlipidemia and hypercholesterolemia. Use of niacin in low doses usually leads to few adverse drug reactions (ADRs); however, at larger doses, niacin can cause skin flushing, itching, and occasionally more serious effects. The 2005 annual report of the American Association of Poison Control Centers documented 3,109 reports of exposures to niacin. During 2006, the Rocky Mountain Poison and Drug Center (RMPDC) in Denver, Colorado, received multiple calls regarding ADRs after nonmedical use of niacin. A review of call records indicated various uses of niacin, including attempts to alter or mask results of urine drug tests, although no scientific evidence exists that ingestion of niacin can alter a drug test result. To determine the extent of niacin use in attempts to alter drug test results, reports to RMPDC of niacin ADRs were reviewed for the period January--September 2006. The results identified 18 persons who reported nonsuicidal, intentional, nonmedical reasons for using niacin, including eight who specified altering drug test results as their reason for using niacin. Ten other persons, among an additional 18 who offered no reason for niacin use, were categorized as possible users of niacin to try to alter drug test results because of their ages or the amount of niacin ingested. Clinicians, especially those whose patients include teens and young adults, should be aware of the potential use of niacin in attempts to defeat urine drug tests.
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PMID:Use of niacin in attempts to defeat urine drug testing--five states, January-September 2006. 1744 21

Niacin is an effective lipid-modifying therapy whose use has been limited by suboptimal tolerability. The adverse effect of flushing is due to prostaglandin D2 (PGD2)-mediated cutaneous vasodilation. Adjunctive treatment with the PGD2 receptor antagonist laropiprant significantly reduces the incidence and severity of niacin-induced flushing. The objective of this study was to assess the effect of aspirin pretreatment on flushing symptoms with extended-release (ER) niacin/laropiprant in healthy volunteers. A randomized, double-blind, placebo-controlled crossover study compared patient-rated flushing following pretreatment with aspirin 325 mg versus placebo administered 30 minutes before ER niacin 2 g/laropiprant 40 mg. Flushing responses were assessed using participant-reported overall symptom severity score (OSSS), including individual characteristics of redness, warmth, tingling, or itching. The overall incidence and severity of flushing were comparable for participants receiving aspirin or placebo before ER niacin 2 g/laropiprant 40 mg. The difference in 3-day average OSSS between treatments was 0.2 (P=.180). Profiles of flushing severity, frequency, and bothersomeness were comparable for the aspirin/ER niacin/laropiprant and ER niacin/laropiprant regimens. All treatments were safe and well tolerated. Coadministration of aspirin 325 mg daily with ER niacin 2 g/laropiprant 40 mg does not further reduce residual flushing symptoms associated with ER niacin 2 g/laropiprant 40 mg alone.
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PMID:Effects of aspirin when added to the prostaglandin D2 receptor antagonist laropiprant on niacin-induced flushing symptoms. 1924 21

Niacin is the most effective lipid-modifying agent for raising high-density lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of English-language literature from January 1, 1985, through April 7, 2009. This search used the title keywords niacin or nicotinic acid crossed with the Medical Subject Headings adverse effects and human. Niacin flushing is a receptor-mediated, mainly prostaglandin D(2)-driven phenomenon, the frequency, onset, and duration of which are largely determined by the distinct pharmacological and metabolic profiles of different niacin formulations. Subjective assessments include ratings of redness, warmth, itching, and tingling. In clinical trials, most (>60%) niacin users experienced mild or moderate flushing, which tended to decrease in frequency and severity with continued niacin treatment, even with advancing doses. Approximately 5% to 20% of patients discontinued treatment because of flushing. Flushing may be minimized by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (alcohol or hot beverages), and taking 325 mg of aspirin 30 minutes before niacin dosing. The current review advocates an initially slow niacin dose escalation from 0.5 to 1.0 g/d during 8 weeks and then from 1.0 to 2.0 g in a single titration step (if tolerated). Through effective counseling, treatment prophylaxis with aspirin, and careful dose escalation, adherence to niacin treatment can be improved significantly. Wider implementation of these measures should enable higher proportions of patients to reach sufficient niacin doses over time to prevent cardiovascular events.
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PMID:A "hot" topic in dyslipidemia management--"how to beat a flush": optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention. 2036 Feb 95

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity.
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PMID:Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera. 2645 62

Five outbreaks of facial flushing accompanied by a feeling of warmth and pruritus were reported in people eating commercially prepared frozen ground beef or processed veal steaks. The outbreaks occurred during a seven-month period in Israel. In all instances niacin (nicotinic acid), a substance known to cause these signs and symptoms was measured in amounts ranging from 0.3 to 6.0 g/kg of raw beef. The chemical was illegally added by two producers in order to enhance color of the meat.
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PMID:Multiple Outbreaks of Niacin (Nicotinic Acid) Intoxication Due to Addition of Meat "Enhancer" to Products by Two Different Meat Processors. 3107 68


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