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)

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.
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PMID:Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. 266 49

Carcinoid tumors are the most frequent gut neuroendocrine tumors accounting for more than 50% of all tumors of the gastroenteropancreatic (GEP) axis. These tumors appear to derive from a stem cell line capable of differentiating into a variety of malignant cells that secrete many different peptides and amines. The symptoms of carcinoid tumors are often non-specific, vague abdominal pain that may precede the diagnosis by a median of 9 years. Carcinoid syndrome occurs in less than 10% of patients. We evaluated the effects of SMS 201-995 in 14 such patients, 12 with diarrhea, 8 with flushing, 3 with wheezing, one with tricuspid valve incompetence, 6 with facial telangiectasia, 3 with a pellagra type dermatosis and one with myopathy. Diarrhea was abolished or significantly reduced in 83%, flushing in 100%, wheezing in 100%, and myopathy improved in the one patient. Blood serotonin was resistant to change, urine 5HIAA fell in 75%, and most gut neuropeptide hormones apart from somatostatin were suppressed. Tumor growth appeared to be slowed in 2/3 of cases treated for up to 4 years. The analog of somatostatin appears to be a useful addition to the therapeutic armamentarium for carcinoid tumors and the symptom complex.
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PMID:Use of somatostatin analog in management of carcinoid syndrome. 292 Jun 54

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.
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PMID:Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. 819 20

Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517 patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day. Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were changes in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety data included adverse events and laboratory values over the 2-year study period. LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week 96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96). Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only modest decreases in total cholesterol (12% and 13%, respectively), whereas total cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and by 28% and 40%, respectively (week 96). All changes from baseline were significant (p <0.001). Niaspan was generally well tolerated, although flushing was common (75%); however, there was a progressive decrease in flushing with time from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was used by one third of patients before Niaspan dosing to minimize flushing episodes. Although serious adverse events occurred in about 10% of patients, none were considered probably or definitely related to Niaspan. Adverse events in general varied widely, but their true relation to the study drug is difficult to ascertain without a placebo (control) group. No deaths occurred. There were statistically significant changes in hepatic transaminases, alkaline phosphatase, direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these changes were mostly small and are not likely to be biologically or clinically significant (the decrease in phosphorus is a new finding in niacin therapy). No myopathy was observed. Thus, this long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation.
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PMID:Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. 991 66

Advicor (lovastatin and extended-release niacin) is the first cholesterol-lowering combination product to become available for the management of hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein (a) and markedly increases high-density lipoprotein cholesterol. These effects are ideal for managing a variety of lipid disorders, including metabolic syndrome. Lovastatin and niacin reduce coronary heart disease mortality in primary and secondary prevention patients, respectively. The extended-release niacin component uses a unique technology to minimize adverse effects (e.g., flushing and hepatotoxicity) while retaining the same lipid-altering effects as immediate-release niacin. The combination product appears to be well tolerated, with discontinuation due to adverse effects other than flushing occurring in a similar percent of patients as for lovastatin in clinical trials. Approximately 9% of patients discontinued the combination product due to flush. No confined cases of myopathy or hepatotoxicity have been reported with this product. Once-daily dosing provides ease of administration that should improve compliance and result in a greater proportion of patients meeting their low-density lipoprotein cholesterol goals. The nomenclature surrounding niacin products used to treat dyslipidemias is confusing. While only two types of niacin formulations exist (immediate-release formulations and formulations which dissolve more slowly than immediate-release formulations), government regulations allow for slowly dissolved niacin formulations to be divided into two types of niacin products; those that are available over-the-counter (OTC) and those that are available by prescription only. Over-the-counter slowly dissolved niacin preparations are not classified as OTC per se, but are considered "nutritional supplements". For this reason, they fall under the jurisdiction of the Federal Trade Commission and do not fall under the umbrella of the FDA branch that controls dyslipidemic products (Endocrine and Metabolic Division of the Center for Drug Evaluation and Research). The slowly dissolved niacin nutritional supplements have not been reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor are they required to meet generic drug rules (even though various brands are available). These brands are described on their labels as "sustained-release", "timed-release", and "slow-release" for example. Only two slowly absorbed niacin products have been approved by the FDA for the treatment of dyslipidemia; they are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to these two products to simplify the terminology and differentiate the products from immediate-release niacin. In this review, we will use "extended-release" to refer to the FDA approved slowly dissolving niacin preparation and "sustained-release" to refer to the nutritional supplements (not FDA approved).
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PMID:Lovastatin and extended-release niacin combination product: the first drug combination for the management of hyperlipidemia. 1197 44

The new combination of niacin extended-release (ER) and lovastatin (Advicor, Kos pharmaceuticals), is a powerful lipid modifying agent and takes advantage of the different mechanisms of action of its two components. Niacin decreases hepatic atherogenic apolipoprotein (apo) B production whereas lovastatin increases apoB removal. Whereas niacin potently increases high density lipoprotein (HDL) levels by decreasing hepatic removal of antiatherogenic apoA-I particles, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors ('statins') appear to increase production of apoA-I. Although there is no outcome data with this combination product, each component has been independently associated with a reduction of cardiovascular event risk by approximately 25 - 35%. The results of a long-term trial in 814 patients, where > 600 had been treated for 6 months and > 200 for 1 year, found reductions of 45 and 42% in low density lipoprotein cholesterol and triglycerides, respectively, at the maximum dose (niacin ER 2000 mg/ lovastatin 40 mg). HDL cholesterol increased by 41%. In addition, the combination decreased lipoprotein (a) by 25% and C-reactive protein by 24%. The niacin ER/lovastatin combination was generally well-tolerated. Flushing was the most common side effect, with approximately 10% of patients intolerant to niacin ER/lovastatin. Hepatotoxicity in this study was 0.5% and myopathy did not occur. Recent studies indicate that niacin can be used safely in diabetic patients who have good glucose control (HbA(1c) < 9%). Once-daily niacin ER/lovastatin exhibits potent synergistic actions on multiple lipid risk factors and represents an effective new agent in the clinical management of dyslipidaemia. Outcome studies are needed to evaluate if combination therapy would result in additive effects on morbidity and mortality.
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PMID:Niacin extended-release/lovastatin: combination therapy for lipid disorders. 1247 73

This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels > or =160 mg/dl without coronary artery disease, or > or =130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a).
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PMID:Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE]). 1263 95

Niacin (nicotinic acid) favourably modifies all aspects of the lipoprotein profile; it raises high-density lipoprotein cholesterol (HDL-C) levels, lowers triglyceride, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) levels and reduces atherogenic small, dense LDL particles. One large monotherapy trial and multiple trials of niacin in combination with other lipid-modifying drugs show remarkable consistency in the ability of niacin to improve angiographic and clinical outcomes. In practice, however, the use of regular, immediate-release niacin (niacin IR) has been limited by the side effect of flushing. Sustained-release (SR) formulations, developed in order to reduce flushing, were found to cause serious hepatotoxicity at varying frequencies. Extended-release niacin (niacin ER; Niaspan), Kos Pharmaceuticals, Inc.) is a prescription formulation of niacin, administered once-daily at bedtime. Niacin ER is as effective in modifying lipoprotein levels as an equal daily dose of niacin IR and it causes less flushing. In addition, niacin ER administered once-daily is not associated with the increased hepatotoxicity reported with SR formulations. Niacin ER has been studied extensively in combination therapy with statins, including lovastatin in a recently introduced combination tablet. Myopathy has not been a substantial problem in statin/niacin ER combination therapy. Finally, a study of niacin ER given to diabetic patients showed only mild trends towards increased glycosylated haemoglobin concentrations and a need for additional antidiabetic medication. Thus, niacin ER represents an effective and safe option in the management of low levels of HDL-C and other lipoprotein abnormalities in a variety of settings.
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PMID:Extended-release niacin for modifying the lipoprotein profile. 1516 82

Niacin extended-release/lovastatin is a new combination product approved for treatment of primary hypercholesterolemia and mixed dyslipidemia. This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings. A total of 4,499 patients with dyslipidemia requiring drug intervention was enrolled at 1,081 sites. Patients were treated with 1 tablet (500 mg of niacin extended-release/20 mg of lovastatin) once nightly for 4 weeks and then 2 tablets for 8 weeks. Patients also received dietary counseling, educational materials, and reminders to call a toll-free number that provided further education about dyslipidemia and niacin extended-release/lovastatin. Primary end points were study compliance, increases in liver transaminases to >3 times the upper limit of normal, and clinical myopathy. Final study status was available for 4,217 patients (94%). Compliance to niacin extended-release/lovastatin was 77%, with 3,245 patients completing the study. Patients in the southeast and those enrolled by endocrinologists had the lowest compliance and highest adverse event rates. Flushing was the most common adverse event, reported by 18% of patients and leading to discontinuation by 6%. Incidence of increased aspartate aminotransferase and/or alanine aminotransferase >3 times the upper limit of normal was <0.3%. An increase of creatine phosphokinase to >5 times the upper limit of normal occurred in 0.24% of patients, and no cases of drug-induced myopathy were observed. Niacin extended-release/lovastatin 1,000/40 mg, dosed as initial therapy, was associated with good compliance and safety and had very low incidences of increased liver and muscle enzymes.
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PMID:Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. 1527 93

Familial combined hyperlipidemia (FCH) is a frequent familial lipid disorder associated with insulin resistance, low HDL cholesterol, high triglycerides and cholesterol levels with variable phenotypes within the same family. FCH is linked to a high risk for cardiovascular diseases. Treatment goals for lipid abnormalities are changing in recent years. Lowering elevated levels of LDL e Non HDL-cholesterol levels are primary targets of therapy. Lower LDL-C than 70 mg/dL seems to be useful to lower cardiovascular risk in patients with very high risk. Many statins are available, with different potencies and drug interactions. Combination therapy of statins and bile acid sequestrants or ezitimibe may be necessary to further decrease LDL cholesterol levels in order to meet guideline goals. High triglycerides and low HDL cholesterol are also important goals in the treatment of these patients, and frequently statins alone are insufficient to normalize the lipid profile. Combination therapy with fibrates will further lower triglycerides and increase HDL cholesterol levels; this combination is also associated with higher incidence of myopathy and liver toxicity; appropriate evaluation of patients' risk and benefits is necessary. Association of statin/niacin seems be very useful in patients with FCH, especially as niacin is the best drug to increase HDL cholesterol; this association is not linked to a higher frequency of myopathy. Niacin causes flushing, that can in part be managed with use of aspirin and extended release forms (Niaspan); niacin also may increase plasma glucose and uric acid levels. Evaluation of risks and benefits for each patient is needed.
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PMID:[Treatment of dyslipidemia: how and when to combine lipid lowering drugs]. 1676 1


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