Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in the general population. Its prevalence doubles with each advancing decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89 years. It is also becoming more prevalent, increasing in men aged 65-84 years from 3.2% in 1968-1970 to 9.1% in 1987-1989. This statistically significant increase in men was not explained by an increase in age, valve disease, or myocardial infarctions in the cohort. The incidence of new onset of AF also doubled with each decade of age, independent of the increasing prevalence of known predisposing conditions. Based on 38-year follow-up data from the Framingham Study, men had a 1.5-fold greater risk of developing AF than women after adjustment for age and predisposing conditions. Of the cardiovascular risk factors, only hypertension and diabetes were significant independent predictors of AF, adjusting for age and other predisposing conditions. Cigarette smoking was a significant risk factor in women adjusting only for age (OR = 1.4), but was just short of significance on adjustment for other risk factors. Neither obesity nor alcohol intake was associated with AF incidence in either sex. For men and women, respectively, diabetes conferred a 1.4- and 1.6-fold risk, and hypertension a 1.5- and 1.4-fold risk, after adjusting for other associated conditions. Because of its high prevalence in the population, hypertension was responsible for more AF in the population (14%) than any other risk factor. Intrinsic overt cardiac conditions imposed a substantially higher risk. Adjusting for other relevant conditions, heart failure was associated with a 4.5- and 5.9-fold risk, and valvular heart disease a 1.8- and 3.4-fold risk for AF in men and women, respectively. Myocardial infarction significantly increased the risk factor-adjusted likelihood of AF by 40% in men only. Echocardiographic predictors of nonrheumatic AF include left atrial enlargement (39%/ increase in risk per 5-mm increment), left ventricular fractional shortening (34% per 5% decrement), and left ventricular wall thickness (28% per 4-mm increment). These echocardiographic features offer prognostic information for AF beyond the traditional clinical risk factors. Electrocardiographic left ventricular hypertrophy increased risk of AF 3-4-fold after adjusting only for age, but this risk ratio is decreased to 1.4 after adjustment for the other associated conditions. The chief hazard of AF is stroke, the risk of which is increased 4-5-fold. Because of its high prevalence in advanced age, AF assumes great importance as a risk factor for stroke and by the ninth decade becomes a dominant factor. The attributable risk for stroke associated with AF increases steeply from 1.5% at age 50-59 years to 23.5% at age 80-89 years. AF is associated with a doubling of mortality in both sexes, which is decreased to 1.5-1.9-fold after adjusting for associated cardiovascular conditions. Decreased survival associated with AF occurs across a wide range of ages.
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PMID:Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. 980 95

The health status of 623 elderly people aged 60 years and over in different residential areas of Beijing was investigated. Among them 289 lived in the Xuanwu district, an urban area, 194 lived in a suburb area of Beijing, the Daxing county and 140 lived in a mountain area of the Huairou county. It was found that the prevalence rates of overweight (BMI 24-27) and obesity (BMI > or = 28), hyperlipidemia and diabetes in urban residents were much higher than that in the suburb and mountain residents (P < 0.01 and 0.05, respectively). The rate of obesity is higher in female than in male (P < 0.05). The rates of overweight and obesity decreased with increase of age (P < 0.001). In subjects with overweight and obesity the rates of hyperlipidemia, hypertension and diabetes were higher than those in the subjects without (P < 0.001). The detected rates of coronary heart disease and calcified valvular heart disease between the four groups with different body weight did not differ significantly.
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PMID:[The investigation of risk factors of cardiovascular diseases in elderly people in Beijing]. 981 55

This review is dealing with currently available medications used in the treatment of obesity. Unfortunately currently available drugs did not prove effective in the long term treatment of obese patients. Fenfluramin and D-Fenfluramin has been withdrawn from the market because of severe side effects as pulmonary hypertension and valvular heart disease. Sibutramin, a serotonin noradrenalin reuptake inhibitor, will be available this year. Orlistat, an inhibitor of pancreatic lipases, has proven effective for weight reduction in obese patients. New drugs as alpha 2-adrenergic antagonists, cholecystokinin, neuropeptide y, bombesin and leptin are in the pipeline.
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PMID:[Drug therapy of obesity]. 987 89

This review evaluates the benefits and potential health risks of the currently used drugs that are approved for the pharmacological treatment of obesity. Analysis of several long term clinical trials indicates that all of these drugs are efficient in reducing excess bodyweight, and that the majority of them allow the maintenance of the reduced bodyweight for at least 1 year. However, the loss of bodyweight attributable to these drugs is in general rather modest, approaching only 0.2 kg per week during the first 6 months of treatment, and at least a partial regain of bodyweight occurs when these drugs are used for periods longer than 1 year. All of these drugs induce several adverse effects. Although most of these adverse effects are mild and transient, the prolonged use of adrenergic or serotonergic anorectic drugs, or their use as combination treatment, may induce serious and potentially life-threatening complications, such as primary pulmonary hypertension or valvular heart disease. The adrenergic appetite-suppressing drugs are not recommended for the treatment of obesity, since their safety has never been evaluated in long term clinical trials, and because of their stimulatory effects on the cardiovascular and nervous systems. The serotonergic drugs, such as fenfluramine and dexfenfluramine, have been the most widely used during the past decade; however, both these compounds have recently been withdrawn from the market, since their use was associated with serious cardiovascular complications. The safety of the prolonged therapeutic use of newer compounds such as sibutramine and orlistat has not yet been demonstrated. Therefore, none of the currently available anti-obesity medications meets the criteria of an 'ideal anti-obesity drug' and, if prescribed, these medications should be used with caution and only under careful medical supervision. Since obesity is recognised as a chronic health-threatening condition, and since classical behavioural therapeutic approaches lack long term efficacy, there is clearly a need for an efficient pharmacological treatment offering an acceptable safety profile. Such a treatment is not available at present. Development of new agents and a more careful assessment of the safety of currently available drugs are needed.
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PMID:A risk-benefit assessment of anti-obesity drugs. 1008 70

Patients in western Sweden who underwent CABG from 1988 to 1991 received prior to coronary angiography and 2 and 5 years after CABG a questionnaire, in which they were asked about symptoms of chest pain and dyspnea. In all, 1,226 patients answered the inquiry prior to CABG, 1,531 patients 2 years and 1,359 patients 5 years after surgery. Both in terms of chest pain and dyspnea there was a marked improvement 2 and 5 years after CABG as compared with prior to surgery. However, between 2 and 5 years after surgery there was a minor deterioration, both regarding chest pain and dyspnea. The most statistically significant preoperative predictors for the occurrence of chest pain more than twice a week 5 years after surgery were concomitant valvular heart disease and obesity.
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PMID:Symptoms of chest pain and dyspnea and factors associated with chest pain after coronary artery bypass grafting. 1054 76

Physicians have struggled with the pharmacological treatment of obesity. In the past, thyroid hormone was often used inappropriately. Dangerous drugs such as dinitrophenol and amphetamines were prescribed, with serious side effects. In the 1980s, a 3 1/2-year study using antiobesity medications with different mechanisms of action supported the theory that patients treated with combination therapy experienced greater weight loss than the placebo-treated patients and that those who remained on therapy were more likely to keep the weight off. Thus, physicians began prescribing "fen-phen" to their patients in the mid-1990s. In 1997, manufacturers voluntarily withdraw the fenfluramines from the market after study results linked their use with valvular heart disease. Since then, two new drugs with different mechanisms of action have been approved for use by the FDA. Sibutramine (Meridia) is a serotonin-norepinephrine reuptake inhibitor acting on the appetite center in the hypothalamus, and orlistat (Xenical) is a pancreatic lipase inhibitor. Research on antiobesity drugs continues. More than 30 potentially new drugs are in various stages of research. It could be years, however, before any of them are proven useful and safe. Antiobesity pharmacology is meant to be used as a tool to treat the disease. Lifestyle changes in the form of diet and exercise patterns are still the crux of therapy.
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PMID:Pharmacological treatment of obesity. Past, present, and future. 1112 76

This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders.
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PMID:Serotonin releasing agents. Neurochemical, therapeutic and adverse effects. 1188 73

A variety of drugs release serotonin (5-HT, 5-hydroxytryptamine) from neurons by acting as substrates for 5-HT transporter (SERT) proteins. This review summarizes the neurochemical, therapeutic, and adverse actions of substrate-type 5-HT-releasing agents. The appetite suppressant (+/-)-fenfluramine is composed of (+) and (-) isomers, which are N-de-ethylated in the liver to yield the metabolites (+)- and (-)-norfenfluramine. Fenfluramines and norfenfluramines are potent 5-HT releasers. (+/-)-3,4-Methylenedioxymethamphetamine ((+/-)-MDMA, "ecstasy") and m-chlorophenylpiperazine (mCPP) are substrate-type 5-HT releasers. Fenfluramines, (+/-)-MDMA, and mCPP release neuronal 5-HT by a common non-exocytotic diffusion-exchange mechanism involving SERTs. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of valvular heart disease, whereas the latter activity is implicated in the anorexic effect of systemic fenfluramine. Appetite suppressants that increase the risk for developing primary pulmonary hypertension (PPH) are all SERT substrates, but these drugs vary considerably in their propensity to increase this risk. For example, fenfluramine and aminorex are clearly linked to the occurrence of PPH, whereas other anorectics are not. Similarly, some SERT substrates deplete brain tissue 5-HT in animals (e.g., fenfluramine), while others do not (e.g., mCPP). In addition to the established indication of obesity, 5-HT releasers may help treat psychiatric disorders, such as drug and alcohol dependence, depression, and premenstrual syndrome. Viewed collectively, we believe new medications can be developed that selectively release 5-HT without increasing the risk for adverse effects of valvular heart disease, PPH, and neurotoxicity. Such agents may be useful for treating a variety of psychiatric disorders.
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PMID:Therapeutic and adverse actions of serotonin transporter substrates. 1216 29

Anorectic drugs are widely used for the treatment of obesity. They are thought to decrease appetite through their effects on catecholamine or 5-hydroxytryptamine (5-HT) levels in the brain. Their use has been associated with epidemics of pulmonary hypertension and the development of valvular heart disease, hypertension, stroke and digital or mesenteric ischemia. Understanding the mechanism of the cardiovascular toxicity of anorectic drugs is important because of the modern epidemic of obesity and the resulting plethora of new anorexigens, many of which share similar mechanisms with those that have previously caused cardiovascular disease. In addition, the mechanism by which anorexigens cause vascular disease has relevance to the etiology and treatment of pulmonary and systemic hypertension. Recent discoveries have clarified how the anorexigens cause vasoconstriction and hypertension. Most anorexigens directly inhibit voltage-gated K+ (KV) channels in vascular smooth muscle cells (SMCs). This reduced K+ efflux leads to depolarization, the opening of voltage-sensitive Ca2+ channels, an increase in intracellular Ca2+ and vasoconstriction. Endothelial dysfunction appears to be a predisposing factor for the development of anorectic-induced vascular complications. Vasoconstriction is weak at clinically relevant doses of anorectic drugs. However, when nitric oxide synthase is inhibited, vasoconstriction is significantly enhanced. Anorexigens are the only drugs in widespread clinical use that have KV-channel-blocking properties and it is probable that much of their cardiovascular toxicity relates to this mechanism. Investigators need to examine new anorexigens and other therapeutic molecules for inhibitory effects on KV channels, as this effect may be a marker of drugs that will elicit vascular complications.
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PMID:Anorectic drugs and vascular disease: the role of voltage-gated K+ channels. 1237 23

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.
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PMID:Pharmacological management of obesity. 1247 68


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