Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used 4 escalating doses (niacin/lovastatin in milligrams): 500/10 for the first month, 1,000/20 for the second, 1,500/30 for the third, and 2,000/40 for the fourth month through week 52. Dose-dependent effects were observed for all major lipid parameters. At week 16, mean low-density lipoprotein (LDL) cholesterol and triglycerides were reduced by 47% and 41%, respectively; mean high-density lipoprotein (HDL) cholesterol was increased by 30% (all p <0.001). LDL/HDL cholesterol and total/HDL cholesterol ratios were also decreased by 58% and 48%, respectively. These effects persisted through week 52, except for the mean increase in HDL cholesterol, which had increased to 41% at 1 year. Lipoprotein (a) and C-reactive protein also decreased in a dose-related manner (by 25% and 24%, respectively, on 2,000/40 mg; p <0.01 vs baseline). Treatment was generally well tolerated. The most common adverse event was flushing, which caused 10% of patients to withdraw. Other adverse events included gastrointestinal upset, pruritus, rash, and headache. Drug-induced myopathy did not occur in any patient. The incidence of elevated liver enzymes to >3 times the upper limit of normal was 0.5%. Once-daily niacin/lovastatin exhibits substantial effects on multiple lipid risk factors and represents a significant new treatment option in the management of dyslipidemia.
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PMID:Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. 1189 8

There have been recent increases in the number of female participants in HIV clinical trials and the number of studies addressing the influence of sex on HIV infection. The findings of some studies indicate a potential sex differences in the frequency and severity of adverse reactions to antiretroviral drugs. This article reviews the available data on the incidence and characteristics of potential sex differences in adverse reactions to certain nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Adverse effects for which a sex difference has been reported include lactic acidosis, rash, elevation in liver enzymes, dyslipidemia, and insulin resistance. The reasons for these sex differences in adverse drug events are unclear but may include differences between men and women in body mass index and fat composition, hormonal effects on drug metabolism, or the effects of genomic constitutional differences on the levels of various enzymes. These differences warrant further study.
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PMID:Sex differences in adverse reactions to antiretroviral drugs. 1271 43

In a large HIV-specialty private practice, patients with undetectable or low-grade-positive viral loads with neuropsychiatric side effects or elevated lipids were switched from efavirenz-to nevirapine-based antiretroviral regimens. This is a retrospective analysis of virologic efficacy and changes in adverse neuropsychiatric effects and serum lipid levels after this switch. Forty patients were evaluated. Thirty-six had undetectable viral loads prior to the treatment switch, and their levels remained undetectable after the switch for a median of 25 months (range, 6 to 59 months). Four patients had persistently low-grade-positive viral loads before the switch; viral loads in two of the four patients remained low-grade-positive, while the levels in two patients became undetectable. Twenty patients reporting neuropsychiatric symptoms (depression, anxiety, or fatigue with or without sleep disturbances) before the switch demonstrated significant improvement, with complete resolution of symptoms in 15 patients. Four patients with isolated sleep disturbances had significant improvement. No rash developed in any patient during the switch. Mean lipid levels improved significantly following the switch. Mean total cholesterol decreased 17.8 mg/dL; low-density lipoprotein cholesterol decreased 25.5 mg/dL; triglycerides decreased 70.1 mg/dL; and high-density lipoprotein cholesterol increased 5.3 mg/dL (all p < 0.05). These results demonstrate that patients who are virologically controlled on efavirenz-containing regimens with treatment-associated side effects can be successfully switched to nevirapine-containing therapy with maintenance of virologic control, reduction in neuropsychiatric side effects, and improvement in dyslipidemia.
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PMID:Switch from efavirenz to nevirapine associated with resolution of efavirenz-related neuropsychiatric adverse events and improvement in lipid profiles. 1689 23

Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B; high triglycerides, low high-density lipoprotein (HDL) cholesterol and apoA1; and high lipoprotein(a) (lp[a]). We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacin(ER)) formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels > or = 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg) and niacin(ER) (500 mg) combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg) and niacin(ER) (1000 mg). An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10%) were lost to follow-up and 4 (3%) withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL) at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 +/- 27, 206.3 +/- 27, 189.8 +/- 31, and 174.9 +/- 27 mg/dL; LDL cholesterol 153.4 +/- 22, 127.3 +/- 21, 109.2 +/- 27, and 95.1 +/- 23 mg/dL; triglycerides 171.1 +/- 72, 159.5 +/- 75, 149.2 +/- 45, and 135.2 +/- 40 mg/dL; HDL cholesterol 45.6 +/- 7, 48.9 +/- 7, 51.6 +/- 9, and 53.9 +/- 10 mg/dL; lp(a) 48.5 +/- 26, 40.1 +/- 21, 35.4 +/- 21, and 26.9 +/- 19 mg/dL; and apoA1/apoB ratio 0.96 +/- 0.7, 1.04 +/- 0.4, 1.17 +/- 0.5, and 1.45 +/- 0.5 (p < 0.01). The percentage of decline in various lipids at 4, 12, and 24 weeks was: total cholesterol 11.8%, 18.8%, and 25.2%; LDL cholesterol 17.0%, 28.8%, and 38.0%; triglyceride 6.8%, 12.8%, and 21.0%; lp(a) 17.5%, 26.9%, and 44.5% respectively (p < 0.01). HDL cholesterol and apoA1/apoB increased by 7.2%, 13.1%, and 18.2%; and 7.9%, 21.9%, and 51.6% respectively (p < 0.01). Target LDL levels (< 100 mg/dL in subjects with manifest coronary heart disease or diabetes; < 130 mg/dL in subjects with > 2 risk factors) were achieved in 92 (80.7%) patients. No significant changes were observed in systolic or diastolic blood pressure, blood creatinine, transaminases, or creatine kinase. A fixed dose combination of lovastatin and niacin(ER) significantly improved cholesterol lipoprotein lipids as well as lp(a) and apoA1/apoB levels in Asian Indian dyslipidemic patients. Satisfactory safety and tolerability profile in this population was also demonstrated.
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PMID:Evaluation of efficacy and safety of fixed dose lovastatin and niacin(ER) combination in asian Indian dyslipidemic patients: a multicentric study. 1731 73

Underlying causes and precipitating causes of heart failure (HF) should be treated when possible. Persons with HF and normal left ventricular ejection fraction (LVEF) should have maintenance of sinus rhythm, treatment of hypertension, myocardial ischemia, dyslipidemia, and anemia, slowing of the ventricular rate below 90 bpm, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers and angiotensin-converting enzyme (ACE) inhibitors. If persons are unable to tolerate ACE inhibitors because of cough, angioneurotic edema, rash, or altered taste sensation, angiotensin II type I receptor antagonists (ARBs) should be given. If HF persists despite diuretics, beta blockers, and ACE inhibitors or ARBs, isosorbide dinitrate plus hydralazine should be administered. Beta blockers, verapamil, diltiazem, and digoxin may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with HF in sinus rhythm with normal LVEF. Exercise training should be encouraged in persons with mild to moderate HF to improve functional status and to decrease symptoms.
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PMID:Treatment of heart failure with normal left ventricular ejection fraction. 1802 14

Implementation of combination antiretroviral therapies has transformed the prognosis of HIV infection during the past decade. Because of its low-pill burden, convenient administration once or twice daily without food restrictions and, in the case of nevirapine, favorable metabolic profile and proven safety in pregnant women and newborns, nonnucleoside reverse transcriptase inhibitors have been shown to be often superior to protease inhibitors as third agents in combination with a backbone of two nucleoside reverse transcriptase inhibitors. Therefore, two nucleoside reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor are currently the most popular used first-line therapies. Hepatotoxicity during the first weeks of therapy with nevirapine, particularly when initiated in women with CD4 counts > 250 cells/mm3, has prompted changes in guidelines and led to a modification in the product label. Recent data, however, suggest that virologically suppressed patients under any other antiretroviral drug combination may safely switch to nevirapine as a part of a simplification strategy, regardless of their current CD4 count. This subset of patients does not show an increased risk of hepatotoxicity or rash with elevated CD4 counts, as has been reported in drug-naive HIV persons. This information is important and may expand the number of candidates who could benefit from nevirapine use, since a substantial proportion of HIV patients show metabolic abnormalities (dyslipidemia, insulin resistance, liver steatosis) and are at increased cardiovascular risk. Fortunately, many of these conditions may ameliorate or improve using nevirapine.
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PMID:Risk for immune-mediated liver reactions by nevirapine revisited. 1861 21

Etravirine (ETR) is the first representative of a new generation of non-nucleoside reverse transcriptase inhibitors (NNRTI) and is indicated in patients with HIV infection and virological failure. The recommended dose is 200 mg (two tablets) every 12 hours after a meal. ETR has good tolerability and the tablets can be dissolved in water, which can aid swallowing in some patients. This drug has a plasma half-life of 30-40 hours and consequently is a candidate for once-daily regimens. The most frequent adverse effect is rash (affecting 19% of patients), which is usually mild (grades 1 or 2) and does not lead to drug withdrawal. The DUET 1 and 2 studies, which compared ETR versus placebo, with both groups receiving boosted darunavir and an optimized background regimen, did not demonstrate a higher incidence of liver toxicity, neuropsychiatric symptoms, gastrointestinal disturbances or atherogenic dyslipidemia in patients receiving ETR. The safety profile of ETR suggests that it could be used as a substitute drug in patients with toxicity induced by first-generation NNRTIs or other antiretroviral drugs.
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PMID:[Safety and tolerability of etravirine]. 2011 24

Intrahepatic Cholestasis of Pregnancy (ICP) constitutes the most common, reversible liver disease closely connected with pregnancy and spontaneously resolving in puerperium. ICP usually reoccurs in consecutive pregnancies (45-90%), often in a more intensified form. Many compounds (hormones, cytokines, medicines, endotoxins) can impair transport in the hepatocyte, disturb the intracellular transport and increase the permeability of the intercellular connections. As a result, the elements of bile may appear in the peripheral blood. Gestational cholestasis constitutes a classic example of intrahepatic cholestasis. The etiology of ICP is multifactorial with hormonal, genetic and environmental factors participating in the process. The diagnosis is based on the presence of pruritus, elevated values of bile acids in the blood serum and of aminotransferases (aspartic, aminopropionic and gamma-glutamylotranspeptydase (AspAt, AlAt, GGTP)), as well as spontaneous remission in the second or third week after childbirth, of lack of other illnesses causing pruritus and icterus. Clinical and biochemical symptoms of ICP include: pruritus without skin rash (usually after 30 weeks of gestation), mild icterus, steatorrhea etc. Abnormalities in the laboratory tests of the LFT (liver function tests) encompass: an increase in the serum concentration of fatty acids (BA) which can be the first and only laboratory abnormality. Concentrations surpassing 10 micromol/l are considered to be abnormal. Concentration of BA higher than 40 micromol/l allows to recognize a case of severe ICP, connected with the risk of premature delivery presence of the meconium liquor, surgical means of delivery and low APGAR score of the newborn (< 7 pt). In about 80% of pregnant women with ICP, the BA concentration ranges between 10-40 micromol/l, but perinatal results are comparable with uncomplicated pregnancies. Some authors are of the opinion that abnormal AlAt value is the most sensitive test, other authors consider the abnormal values of alkaline phosphatase and bilirubin to be the most pathognomonic factors. Other abnormal tests include: higher activity of alpha-hydroxybutyric dehydrogenase correlated with an increase of the alkaline phosphatase and bilirubin; mild metabolic acidosis; dyslipidemia with elevated concentrations of the total lipids, total cholesterol and free LDL cholesterol and apolipoprotein; abnormal glucose tolerance test. ICP constitutes a medical problem that carries a considerable risk for the fetus, resulting from an increased flow of bile acids to the fetal blood circulation (elevated level in the amniotic fluid, in the umbilical blood serum and meconium). The risk of adverse effects for the fetus correlates with the rise of BA concentration in maternal blood serum. Cholestasis increases the risk of premature labor, presence of meconium in the amniotic fluid, fetal bradycardia, intrauterine asphyxia and stillbirth, particularly when the concentration of serum bile acids on an empty stomach is above 40 micromol/l. However, maternal clinical signs and symptoms do not correlate with the fetal outcome. Aspiration of bile acids or their accumulation in the fetal blood circulation are responsible for the increased frequency of RDS appearing in ICP. The aim of the obstetric management of ICP is to reduce maternal symptoms and biochemical disorders and to minimize the risk of premature delivery fetal distress and sudden death. ICP management should include: bed regime, light, low-fat diet, no stress, upper abdomen ultrasound examination, LFT tests and thrombotic tests once a week, monitoring of the fetal well-being with the available biophysical methods, pharmacotherapy and therapeutic termination of pregnancy in case of serious illness and/or the fetal distress. Ursodeoxycholic acid (UDCA) is the basis of the pharmacological treatment of pregnant women and currently constitutes the most promising treatment option of ICP. UDCA is administered orally in the dosage of 10-16 mg/kg/24, what in practice means 250-300 mg/2-3 times a day.
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PMID:[Clinical practice guidelines of the Team of Experts of the Polish Gynecological Society: management of the intrahepatic cholestasis of pregnancy]. 2334 3

There are four classes of antiretroviral agents used in the treatment of HIV/AIDS. Adverse effects to Highly Active Antiretroviral Therapy (HAART) are common and often difficult to avoid. In many cases, research is not able to identify the exact cause of an adverse event. The severity of adverse reactions varies greatly and difficult to manage; typically prevention is more desirable than treatment. However, this is not always true. This paper will review safety aspect of class-wide Highly Active Antiretroviral Therapy, mechanism of action. A class-wide adverse effect for Reverse transcriptase inhibitors includes lactic acidosis, peripheral neuropathy and lipoatrophy. Class wide adverse effects to non-nucleoside reverse transcriptase inhibitors include rash and hepatotoxicity, while efavirenz has its own unique CNS reactions. Protease inhibitor side effects include hyperglycemia, lipoaccumulation, dyslipidemia, and gastrointestinal (GI) intolerance. Coreceptor CCR5 antagonists, which provide a novel mechanism of action, are a recent addition to the armamentarium of antiretroviral agents. Antiretroviral are an important break-through in the treatment of HIV/AIDS. However, adverse reactions from these drugs can range from mild to life-threatening, and determining which agent is the cause is frequently difficult to discern. Fortunately, side effects can be monitored, treated and in many cases, prevented.
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PMID:Safety Aspects of Antiretroviral Therapy for Management of HIV Infection. 2520 54

Male, of 69 years old, caucasian, farmer, non smoker, with hypertension, dyslipidemia and past pesticide exposition, without known familiar diseases. In October/2005, he initiated dyspnoea and asthenia for moderate efforts, cough and night sibling, with persisted although several antibiotic treatments were done. In December/2005, he went to the Emergency department, where it was seen a right pleural effusion. The pleural liquid study, the bronchofiberscope examination, the biopsy and the studies for cancer staging allowed the diagnosis: Lung Adenocarcinoma stage IIIB (positive pleural effusion) - December 2005. He was submitted to thoracocentesis, pleurodesis and local radiotherapy. He carried through citostatic treatment with Gemcitabine-Carboplatin from 16/02/2006 to 13/07/2006, with some haematological toxicity. The follow up showed progression disease, initiating second line of treatment with Erlotinib 150mg, at 21/08/2006. He maintains the same treatment with disease stability and a general good condition, only showing a grade II rash (face, forearms and hands) as secondary effect of treatment. Rev Port Pneumol 2008; XIV (Supl 3): S83-S86.
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PMID:Long survival with erlotinib as second line treatment in non-small cell lung cancer. 2596 93


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