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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To develop an appropriate combination of ephedrine and caffeine consisting of clinically relevant doses, we examined the acute thermogenic, metabolic, and cardiovascular effects of different doses of caffeine (C) and ephedrine (E) given separately and in combination to normal subjects. The thermogenic effect after E+C (20 mg/200mg) was larger than that of any other combinations, and E and C exerted a supra-additive synergism on thermogenesis and systolic blood pressure, while being without effect on diastolic blood pressure. The combination also had pronounced effects on glucose metabolism by increasing plasma glucose, insulin and C-peptide concentrations. During chronic treatment the effect of E+C on energy expenditure is maintained, while side effects subside because tolerance develops to its hemodynamic and metabolic effects. During dietary energy restriction E+C promotes fat loss and preserves fat-free mass, which may contribute to its chronic effect on energy balance. In conclusion, the hemodynamic and side effects to E+C are transient during chronic treatment, while the effect on energy expenditure persists. The compound also possesses repartitioning properties, which may be useful in the treatment of obesity.
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PMID:Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. 838 79

Obesity is common enough to constitute a serious medical and public health problem. Drug prescription for obese patients is difficult since dosages based on pharmacokinetic data obtained in normal-weight individuals could induce errors. In obese patients, physiopathological modifications are likely to affect drug tissue distribution and elimination. Body constitution is characterised by a higher percentage of fat and a lower percentage of lean tissue and water. Although the cardiac output and total blood volume are increased, the blood flow per gram of fat is less than in nonobese individuals. Histological hepatic alterations are commonly reported in morbidly obese individuals. A higher glomerular filtration rate is also observed. Most of the pharmacokinetic information concerning obesity deals with distribution. Published data concerning molecules with moderate and weak lipophilicity are homogeneous. In obese compared with normal weight individuals, the total volume of distribution (Vd) is moderately increased (aminoglycosides, caffeine) or similar (H2-blockers, neuromuscular blockers), but the Vd corrected by kilogram of actual bodyweight is significantly smaller. These drugs distribute to a limited extent in excess bodyweight. For highly lipophilic drugs, despite this common characteristic, discrepancies in distribution in obesity exist between drugs belonging to different pharmacological classes. Some drugs show a clear augmentation of Vd and elimination half-life (benzodiazepines, carbamazepine, trazodone, verapamil, sufentanil), indicating a marked distribution into adipose tissue. For others, Vd and Vd/kg are decreased (cyclosporin, propranolol), suggesting that factors other than lipid solubility intervene in tissue distribution. As a general trend, the total clearance (CL) of drugs metabolised by oxidation, conjugation or reduction, and also of drugs with flow-dependent hepatic clearance, is not diminished in obesity. Usually CL is identical in obese and nonobese individuals, sometimes it is increased in obesity (enflurane, halothane, prednisolone, some benzodiazepines). With some drugs a significant reduction in CL is observed in obese individuals (methylprednisolone, propranolol). Renal clearance of aminoglycosides and cimetidine increases in obese individuals. Practical guidelines for dosage adjustment are proposed. For drugs with distribution restricted to lean tissues, the loading dose should be based on the ideal bodyweight of patients. For drugs markedly distributed into fat tissue the loading dose is based on total bodyweight. Adjustment of the maintenance dose depends on possible changes in CL. In some cases (atracurium, prednisolone) dosage adjustment does not follow these recommendations, owing to pharmacodynamic data.
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PMID:Clinical pharmacokinetics of drugs in obesity. An update. 840 34

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
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PMID:Combined drug treatment of obesity. 869 49

Extremes of intracranial pressure commonly cause headache. Benign intracranial hypertension is a rare syndrome of increased intracranial pressure manifesting as headache, intracranial noises, transient visual obscuration, and palsy of the sixth cranial nerve. Endocrine disorders such as obesity and hypoparathyroidism, hypervitaminosis A, tetracycline use and thyroid replacement are probable causes of benign intracranial hypertension. In the majority of cases, however, it is idiopathic. Benign intracranial hypertension is though to be caused by cerebral edema, high cerebrospinal fluid outflow resistance and high cerebral venous pressure, or a combination of the three. The management of benign intracranial hypertension includes, symptomatic headache relief, removal of offending risk factor(s), and medical or surgical reduction of intracranial pressure. Spontaneous intracranial hypotension is more rare than benign intracranial hypertension. Postural headache (worse in the upright position) is the hallmark of spontaneous intracranial hypotension. Typically, the cerebrospinal fluid pressure is less than 60 mm H2O. Diminished cerebrospinal fluid production, hyperabsorption, and leak are postulated mechanisms of spontaneous intracranial hypotension. Empirical treatment includes bed rest, administration of caffeine, corticosteroids or mineralocorticoids, epidural blood patch, and epidural saline infusion.
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PMID:Headache caused by raised intracranial pressure and intracranial hypotension. 883 14

Changes in food intake, serum adipsin, and obesity were evaluated in the MSG-treated mouse. In Experiment 1, mice treated with MSG had 50% lower serum adipsin and over 2-fold higher percentage of body fat than the lean controls. Both feeding caffeine and restricting intake normalized serum adipsin and caused weight loss, but did not normalize the percentage of body fat. No additional effect was gained by feeding isoproterenol or ephedrine in combination with caffeine. In Experiment 2, we separated the direct effect of caffeine from the associated depression in intake using a paired feeding design, and also determined the effects of selected adrenergic agents and somatotropin (S). Somatotropin increased weight gain and reduced the percentage of body fat in healthy and obese mice, and tended to lower serum adipsin. Caffeine clearly depressed intake, caused weight loss, and increased serum adipsin, but similar results were achieved by restricting intake. None of the adrenergic drugs tested changed serum adipsin. Ephedrine depressed food intake and caused weight loss, but reduced the percentage of body fat only at the highest dietary concentration (2000 mg per kg of diet). Phenylephrine reduced weight gain without a concomitant effect on the percentage of body fat, and isoproterenol did not influence weight gain or body fat.
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PMID:Regulation of adipsin and body composition in the monosodium glutamate (MSG)-treated mouse. 891 74

The acceptance of medication as a legitimate adjunct to diet and behavior modification in the treatment for obesity is an emerging phenomenon spurred by advances in understanding the biologic basis of body weight regulation and by the demonstration of safe and effective chronic maintenance of weight loss using a pharmacobehavioral approach. The decision to medicate for obesity depends on good clinical judgment based on such considerations as body mass index; body composition; body fat dissociation; age; sex; and comorbid conditions, such as diabetes and hypertension. Several nonadrenergic agents and a serotonergic agent have FDA-approved indications for weight loss. Phenylpropanolamine is available over the counter. Clinical trials support the efficacy of fluoxetine and ephedrine or caffeine in producing weight loss, although these agents do not have FDA-approved indications for treatment for obesity. In addition, new agents are being developed or are anticipated for approval. The use of existing agents in combination and their use adjunctive to diet and behavioral approaches to obesity treatment are fertile areas for research. The expectant attention to this subject is demanded by the imperative that the health in one three people in the United States is adversely affected by obesity.
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PMID:Medicating the obese patient. 897 57

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

There is evidence that drugs altering food intake such as dexfenfluramine, sibutramine and orlistat have useful therapeutic effects, with an acceptable side effect profile. 'Thermogenic' drugs, such as ephedrine and caffeine, are also effective, but less well tolerated and may, in any case, work by producing anorexia. The state of drug treatment for obesity now is similar to the early days of antihypertensive treatment in the 1960s when reserpine, ganglion blockers and nonselective adrenergic blocker were all that was available. There is considerable reason for optimism that the next 10 years will bring better treatments for the obese.
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PMID:Present and future pharmacological approaches. 924 43

Obesity is a multifactorial and complex affectation that is characterized by a long-term excess energy intake (EI) above energy expenditure (EE). Since fat oxidation seems to be dependent on SNS activation and also seems to remain acutely unaffected by fat intake, this macronutrient is certainly partly responsible for this situation. In addition, high-fat intake does not induce as potent satiety signals or a compensation effect on subsequent EI as do diets rich in carbohydrates or proteins. Moreover, since alcohol intake acutely inhibits fat oxidation and does not promote subsequent compensation for its energy content, it should consequently be regarded as a substrate which can induce a positive energy balance under free-living conditions. Thus, in a weight reducing context, each energy substrate should be manipulated while taking into account its specific characteristics. Obesity has also often been associated to a decreased sympathetic nervous system (SNS) activity, hence sympathomimetic agents have been proposed as a possible way to partially correct this situation. Two of these agents are the widely consumed caffeine (CAF) and the pungent principle of hot red pepper, capsaicin (CAP), which acutely increase EE and reduce EI under some circumstances. Furthermore, other factors like dietary fibers, that have been shown to increase satiety and fullness, and reduce EI in some cases, should also be considered.
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PMID:Food intake, energy balance and body weight control. 942 60

Low caloric diet is a commonly accepted treatment in obesity. However, owing to moderate results, a pharmacological support has been proposed. As some efficacious drugs activate overall sympathetic activity, they might modify functions of the cardiovascular system. Three groups of subjects were studied: (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg); (3) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg) and yohimbine (2 x 5 mg). The cardiovascular state was evaluated by thoracic electrical bioimpedance, automatic sphygmomanometry and continuous ECG recording. In each patient, the haemodynamic study was performed twice: at rest, i.e. before treatment; and after 10 days of treatment. On the same days in each patient, the haemodynamic tests were performed during physical exercises (handgrip stress and cycloergometer exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients. These two drugs led to an increase in ejection fraction during cycloergometer exercise. Addition of yohimbine increased diastolic pressure and heart rate but decreased ejection fraction and stroke index during rest. We also observed that addition of yohimbine decreased ejection fraction during the handgrip and cycloergometer exercise and increased cardiac load during dynamic exercise. Pharmacological supplement of ephedrine and caffeine to a low caloric diet modified the cardiovascular system weakly, but the addition of yohimbine to this regimen attenuated cardiac performance during rest and handgrip and increased cardiac work during dynamic exercise.
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PMID:Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women. 954 23


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