Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Until recently, obesity did not play a major role in considerations of physicians and public health authorities. The impact of health-threatening overweight was so far considered only as a risk factor for various other serious illnesses, such as hypertension, diabetes mellitus, hyperuricemia, elevated blood lipid levels and of vascular diseases of the heart, the brain and the kidneys. Recently however, obesity has been rated by the WHO as an unique disease, resulting in elevated morbidity and mortality. It is of constantly increasing importance because of the raising number of obese individuals in all industrial countries. In Austria an incidence of 8.5% of the adult population is estimated to be obese with a BMI > 30. Though the established concept for treatment of overweight consists of reduction of the caloric intake by diet, there is an obvious need for drugs making dieting easier acceptable to obese patients for prolonged periods. Orlistat is the first representative of a new class of such drugs, inhibiting intestinal acting lipase thus reducing the intestinal absorption of triglycerides; it contributes, therefore, to a reduced calorie intake. Preliminary results of treatment studies with Orlistat are presented, demonstrating its efficacy in inducing weight loss and improving metabolic parameters with tolerable intestinal side effects. After finalization of international studies, demonstrating efficacy and tolerability, orlistat has been registered in Austria in September 1998.
 ...
PMID:[Reduction of obesity and improvement in metabolic parameters by inhibition of intestinal lipases: current results with orlistat]. 987 90

Obesity is an increasing health problem in most developed countries and its prevalence is also increasing in developing countries. There has been no great success with dietary means and life style modification for permanent weight loss. Various surgical treatment methods for obesity are now available. They are aimed at limiting oral energy intake with or without causing dumping or inducing selective maldigestion and malabsorption. Based on current literature, up to 75% of excess weight is lost by surgical treatment with concomitant disappearance of hyperlipidaemias, type 2 diabetes, hypertension or sleep apnoea. The main indication for operative treatment is morbid obesity (body mass index greater than 40 kg/m2) or severe obesity (body mass index > 35 kg/m2) with comorbidities of obesity. Orlistat is a new inhibitor of pancreatic lipase enzyme. At doses of 120 mg three times per day with meals it results in a 30% reduction in dietary fat absorption, which equals approximately 200 kcal daily energy deficit. In the long term, orlistat has been shown to be more effective than placebo in reducing body weight and serum total and low-density lipoprotein cholesterol levels. Orlistat has a lowering effect on serum cholesterol independent of weight loss. Along with weight loss, orlistat also favourably affects blood pressure and glucose and insulin levels in obese individuals and in obese type 2 diabetic patients.
 ...
PMID:New aspects in the management of obesity: operation and the impact of lipase inhibitors. 1009 83

Metabolic syndrome X includes glucose intolerance or type 2 diabetes, dyslipidemia and arterial hypertension which are classical cardiovascular (CV) risk factors. In course of time, other CV risk factors have been added to the syndrome: rheological alterations, endothelial dysfunction, anomalies in the coagulation/fibrinolysis system, microalbuminuria and so on.... Insulin resistance is the cornerstone of metabolic syndrome X, with secondary hyperinsulinism. Upper body obesity is associated with metabolic syndrome X. Simple waist measurements can detect the subjects (10-15% of the population) at increased CV risk with a sensitivity of 70%. This is invaluable for such a simple and cheap test. Diet is the first step in treating these patients and reducing caloric intake is necessary in most of them. Saturated fats will be replaced by polyunsaturated and mono-unsaturated ones. Long-chain carbohydrates with low glycemic index will be suggested. Regular physical activity will be promoted. If these life style modifications fail, drugs can be added: biguanide and glitazone are good candidates. Orlistat has improved metabolic syndrome X on a long-term basis. Drugs that could increase insulin resistance are to be avoided.
 ...
PMID:[The importance of syndrome X in daily practice]. 1119 91

Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.
 ...
PMID:Orlistat in the treatment of obesity. 2694 9

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.
 ...
PMID:Pharmacologic options for the treatment of obesity. 1147 77

The prevalence of hypertension among the obese is twice as high as that in persons of normal weight. Not only the BMI, but, and in particular, the circumference of the waist correlates with blood pressure. A relationship also obtains between BMI and left-ventricular muscle mass, with left-ventricular hypertrophy occurring twelve times more often among the obese than among slim persons. Obesity puts a strain on both the hemodynamics and metabolism of the heart. On the one hand, long-term sequelae include disordered cardiac function extending to cardiomyopathy, on the other, obesity is responsible for sympatho-adrenergic stimulation considered to be a cause of insulin resistance, and is thus, in particular in the hypertensive, closely associated with metabolic syndrome. Specific nondrug treatment options include weight reduction, a low-salt diet and physical exercise. In some cases, Sibutramine and Orlistat may have a supporting role. For the antihypertensive treatment of the obese, drugs with a favorable hemodynamic and metabolic effect should be used.
 ...
PMID:[Hypertension and cardiomyopathy in obesity. Treat the heart simultaneously]. 1169 85

(1) Treatments for obesity are disappointing, and none has yet shown an effect on morbidity or mortality. Non drug treatments have not been assessed adequately. Long-term maintenance of weight loss requires long-term patient management. (2) Orlistat, a gastrointestinal lipase inhibitor, is licensed in Europe for the treatment of obesity, in combination with a low-calorie diet. (3) The risk-benefit ratio of orlistat could not be estimated from the initial assessment file in 1999. There were fears over a possible increase in the risk of breast cancer. (4) Few new efficacy data have been obtained since. Medium-term trials (12-24 months) show that orlistat (120 mg three times a day), combined with dietary intervention, has a minor supplementary effect on weight loss (-3.5 kg on average). (5) A meta-analysis of three of the four available comparative trials lasting two years failed to conclude that orlistat prevents the onset of type 2 diabetes. Likewise, there is no firm evidence that orlistat lowers cardiovascular morbidity or mortality. (6) Orlistat frequently has gastrointestinal adverse effects, and case reports of hypertension have been published. Orlistat probably interacts with a number of other drugs. (7) Follow-up of nearly 8,000 women for only a few years showed no increase in the incidence of breast cancer on orlistat. (8) In practice, dietary intervention and risk factor management remain the cornerstones in the management of obesity. Orlistat is only a minor, optional and temporary aid, although it appears so far to have no serious adverse effects.
 ...
PMID:Orlistat: a second look. At best, a minor adjunct to dietary measures. 1198 67

The growing recognition of the health risks of obesity coupled with the difficulties in treating it successfully by lifestyle modification predicates a need for effective drug treatment. The history of drug treatment in the second half of the 20th century is, however, one of disappointment and concern over drug toxicity. However, the advances in our understanding of the mechanism of weight control, together with improved ways of evaluating anti-obesity drugs, has resulted in two effective compounds, sibutramine and orlistat, becoming available for clinical use. Sibutramine has actions on both energy intake and expenditure and had been shown to enhance weight loss and weight maintenance achieved by diet, in simple obesity as well as when accompanied by complications of diabetes or hypertension. About 50-80% of patients can achieve a >5% loss, significantly more than if patients receive the same lifestyle intervention with placebo. Orlistat, which acts peripherally to block the absorption of dietary fat, has had similar results in clinical trials; a recent study (XENDOS) has just reported results which show that the enhanced, albeit modest, weight loss achieved with orlistat delays the development of diabetes over a 4-year period. A number of other compounds are expected to complete or enter clinical trials over the next decade. There is considerable optimism that we will soon have the pharmacological tools needed to make the treatment of obesity feasible.
 ...
PMID:Pharmacotherapy of obesity. 1246 17

Obesity is a major chronic health problem in adults. It is a complex, multifactorial disorder characterised by excess accumulation of adipose tissue. It is associated with a number of complications including cardiovascular disease, hypertension, type 2 diabetes, dyslipidaemia and cancer. A weight loss in the order of 5-10% is associated with clinically meaningful reductions with respect to all comorbidities. Diet and exercise has been the cornerstone of weight management therapy, but this approach has limitations, especially for weight maintenance. Previous drugs used in obesity had serious side effects including valvular heart disease. However, recent drugs like orlistat and sibutramine have been rigorously tested and proven safe. Orlistat, a lipase inhibitor, inhibits absorption of dietary fat by approximately 30%. Taken with a hypocaloric diet, it produces and maintains clinically meaningful weight loss. Sibutramine is a centrally-acting agent which enhances satiety and thermogenesis by inhibiting serotonin and noradrenaline re-uptake. It is appropriate for patients who are unable to lose weight by lifestyle modification.
 ...
PMID:Pharmacological management of obesity. 1247 68

Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders. However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.
 ...
PMID:Massive hepatocellular [correction of hepatocullular] necrosis: was it caused by Orlistat? 1248 15


1 2 3 4 Next >>