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

Fluoxetine is a potent and specific inhibitor of 5-HT uptake even after prolonged dosing. Both fluoxetine and norfluoxetine, an active metabolite, have a long plasma half life. The drug is extensively metabolized and undergoes renal elimination. Impairment of renal function, increasing age or obesity do not appear to alter the disposition of fluoxetine, although hepatic impairment predictably decreases the clearance of the drug. Recent data suggests that fluoxetine is an inhibitor of cytochrome P450-II-D6 in man and has been shown to inhibit the metabolism of a number of drugs which are substrates for this isoenzyme. It does not, however, affect the elimination of ethanol and does not enhance the effect of ethanol on psychometric testing. Fluoxetine has no effect on normal blood pressure although mean heart rate is slightly reduced. It does not appear to have a clinically significant effect on pituitary function. Although there is psychometric and EEG evidence to suggest a vigilance enhancing property, fluoxetine does not exhibit stimulant activity of the amphetamine type and has been shown to be well tolerated at doses clinically useful for appetite suppression in extensive clinical trials and widespread clinical use since marketed in 1987 for depressive illness.
 ...
PMID:The human pharmacology of fluoxetine. 133 86

Fluoxetine is a highly specific serotonin reuptake inhibitor. In studies that used a dose of 60 mg once daily, fluoxetine-treated patients consistently had greater weight loss than placebo-treated patients. In six double-blind, placebo-controlled studies of 6-8 wk duration, mean weight changes on fluoxetine were approximately 0.5 kg/wk. Longer term studies have shown maximum mean weight loss to occur at 12-20 wk of therapy. Studies have consistently shown improvements in indices of glycemic control as well as weight loss in obese diabetic patients. Safety analysis has been performed on data from 3491 obese patients in controlled clinical trials of up to 52 wk duration. Adverse events with an incidence of greater than 5%, which were reported significantly more frequently by fluoxetine-treated patients, were headache, asthenia, nausea, diarrhea, somnolence, insomnia, nervousness, sweating, and tremor. Fluoxetine is effective, well tolerated, and safe in the treatment of obesity and obese diabetics.
 ...
PMID:Clinical studies with fluoxetine in obesity. 172 31

In summary, fluoxetine is a highly selective serotonin uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other serotonin uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by serotonin uptake inhibition. Its selectivity for the serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of serotonin in modulating human pathophysiologies.
 ...
PMID:Fluoxetine, a selective inhibitor of serotonin uptake. 199 52

Portal blood flow was measured by means of direct bolus imaging (DBI), a method of measuring flow velocity with magnetic resonance imaging. DBI allows immediate visualization of fluid movement, thereby enabling calculation of a flow velocity from fluid displacement. In a study of 14 healthy male volunteers, portal blood flow was measured with electrocardiographic gating during the 18 seconds subjects could suspend respiration. These measurements showed a close correlation (r = .968) with those obtained by means of Doppler ultrasound (US). Increases in portal blood flow after oral administration of ethanol and glucose were measured with DBI. Glucose caused a statistically greater increase in portal blood flow volume in healthy control subjects than in patients with chronic hepatitis. Blood sugar, on the other hand, showed a significantly greater increase in these patients, possibly reflecting the greater vascular resistance of the liver. DBI is a useful noninvasive method of measuring portal blood flow without the limitations imposed on Doppler US by obesity and intestinal gas.
 ...
PMID:Portal blood flow: measurement with MR imaging. 268 71

Health risks associated with obesity are well known and compliance with standard regimens for weight reduction is frequently unsatisfactory. Fluoxetine is a specific inhibitor of serotonin re-uptake with very minimal affinity for serotonergic or other receptors. It causes a decrement in food intake in animals. Placebo or fluoxetine was given for up to 8 weeks to non-depressed, otherwise healthy, obese patients given minimal dietary advice. Patients given fluoxetine lost 4.5 +/- 4.0 kg, significantly more than those receiving placebo, 1.4 +/- 0.1 kg. The weight loss was correlated with the degree of obesity in the fluoxetine-treated patients. Asthenia was the only event reported significantly more frequently by fluoxetine-treated patients (23 percent) than by those treated with placebo (3 percent) (P less than 0.01). Fluoxetine appears to be safe and effective in inducing weight loss over periods of up to 8 weeks.
 ...
PMID:Use of a serotonin re-uptake inhibitor, fluoxetine, in the treatment of obesity. 350 94

Literature on liver morphology in untreated obesity reveals varying prevalences of various pathological findings. The purpose of this literature study was to summarize and evaluate the published observations and to discuss discrepant findings. A complete search was aimed at utilizing bibliographic methods including a computerized survey. Forty-one original articles were included, comprising information on liver morphology in 1515 morbidly obese patients. Liver biopsy was considered normal in 12 per cent of the cases. The most frequent abnormality reported was fatty change, present in 80 per cent of the biopsies. Portal inflammation was also common (33 per cent). Fibrosis, mainly portal or periportal, was observed in 29 per cent. Cirrhosis, however, involved only 3 per cent. Study of relationships between the degree of liver change and certain possible pathogenetic factors (eg degree and duration of obesity, age, sex, alcohol consumption, diabetes mellitus) does not point towards a single causal factor. Co-influence of additional pathogenetic factors are likely in the development of liver changes in morbid obesity.
 ...
PMID:Liver morphology in morbid obesity: a literature study. 637 41

Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Hypogonadotropic hypogonadism is a major characteristic of patients with PWS, and it is speculated to be due to hypothalamic insufficiency. Two adult female patients with PWS and no prior history of menses are presented. Both of these patients were treated with fluoxetine for psychopharmacologic management of obsessive features in the form of food preoccupation and hyperphagia or for compulsive behaviors in the form of severe self-injurious behaviors. The two female patients with PWS who had primary amenorrhea developed vaginal bleeding believed to be menses following at least 6 months of treatment with fluoxetine. Mature hypothalamic function is characterized by pulsatile release of gonadotropin-releasing hormone (GnRH) in a critical range of frequency and amplitude. Central nervous system neurotransmitters may modify GnRH secretion. Fluoxetine specifically inhibits the reuptake of serotonin which may impact the hypothalamic-pituitary-ovarian system in female patients with PWS.
 ...
PMID:Onset of menses in two adult patients with Prader-Willi syndrome treated with fluoxetine. 749 74

Sleep-related eating disorders distinct from daytime eating disorders have recently been shown to be associated with sleepwalking (SW), periodic limb movement (PLM) disorder and triazolam abuse in a series of 19 adults. We now report eight other primary or combined etiologies identified by clinical evaluations and polysomnographic monitoring of 19 additional adults (mean age 40 years; 58% female): i) obstructive sleep apnea (OSA), with eating during apnea-induced confusional arousals (n = 3); ii) OSA-PLM disorder (n = 1); iii) familial SW and sleep-related eating (n = 2); iv) SW-PLM disorder (n = 1); v) SW-irregular sleep/wake pattern disorder (n = 1); vi) familial restless legs syndrome and sleep-related eating (n = 2); vii) anorexia nervosa with nocturnal bulimia (n = 2) and viii) amitriptyline treatment of migraines (n = 1). In our cumulative series of 38 patients (excluding six with simple obesity from daytime overeating), 44% were overweight (i.e. > 20% excess weight) from sleep-related eating. Nightly sleep-related binge eating (without hunger or purging) had occurred in 84% of patients. Onset of sleep-related eating was also closely linked with i) acute stress involving reality-based concerns about the safety of family members or about relationship problems (n = 6), ii) abstinence from alcohol and opiate/cocaine abuse (n = 2) and iii) cessation of cigarette smoking (n = 2). Current treatment data indicate a primary role of dopaminergic agents (carbidopa/L-dopa; bromocriptine), often combined with codeine and clonazepam, in controlling most cases involving SW and/or PLM disorder. Fluoxetine was effective in two of three patients. Nasal continuous positive airway pressure therapy controlled sleep-related eating in two OSA patients.
 ...
PMID:Additional categories of sleep-related eating disorders and the current status of treatment. 810 56

Fluoxetine hydrochloride (Lovan, Eli Lilly and Company, Indianapolis, Indiana, USA), a specific serotonin uptake inhibitor, was compared with placebo in 458 obese outpatients in a 52-week double-blind randomized ten-site trial to study its effect on weight reduction. Patients in the fluoxetine and placebo groups were predominantly Caucasian (81% and 85%, respectively) and female (81% and 79%, respectively), with a mean body mass index (BMI) of 36.2 and 35.8 kg/m2, respectively, and a mean age of 43 years (both groups). Fluoxetine therapy (60 mg/day) resulted in statistically significantly (P < or = 0.05) greater mean weight loss than placebo to week 28. Although some patients continued to lose weight throughout the 52-week therapy period, maximum mean weight loss occurred at week 20. There was no treatment difference at 52 weeks. The change in visit frequency (biweekly to week 8, monthly to week 20, then bimonthly to week 52) may have affected results. Patients with higher baseline BMIs (> 40 kg/m2) attained and maintained a greater weight loss than patients with lower baseline BMIs (< 40 kg/m2). Two sites demonstrated greater efficacy than the study as a whole. The use of nutrition counselling at one site and behaviour modification at the other, or other site-to-site differences, may account for the improved efficacy. Fluoxetine was well tolerated and appeared to be safe therapy for the treatment of obesity with efficacy demonstrated for 28 weeks.
 ...
PMID:Fluoxetine: a randomized clinical trial in the treatment of obesity. 818 9

Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 micrograms/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the 'serotonergic syndrome'. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds.
 ...
PMID:Clinical pharmacokinetics of fluoxetine. 819 83


1 2 3 4 Next >>