Determinantes funcionais e morfológicos de ação de droga sobre os pulmões utilizando um modelo experimental em cobaias sob o uso do cloridrato de fluoxetina / Functional and morphological determinants of drug action on the lungs through an experimental model in guinea pigs under use of fluoxetine

Muito se tem pesquisado sobre os efeitos adversos dos antidepressivos tricíclicos sobre o sistema respiratório, embora sejam poucos com relação a tal aspecto na literatura médica sobre a fluoxetina (Prozac®)- um inibidor seletivo da recaptação da serotonina. As principais indicações clínicas de ambas substâncias- fluoxetina e tricíclicos são os quadros depressivos, obsessivo-compulsivos, ansiedade, Síndrome do Pânico, entre outros. Entretanto, dentre os poucos e raros efeitos adversos descritos na literatura científica, destaca o comprometimento do aparelho respiratório na forma de doença pulmonar intersticial , como a pneumonite de hipersensibilidade e fosfolipidose. O principal objetivo do presente trabalho é verificar a ação da fluoxetina sobre o aparelho respiratório, com relação à mecânica e resposta histopatológica à injúria, particularmente sobre o interstício pulmonar, através de um modelo experimental em cobaias / Although there have been quite a lot references in the medical literature about adverse effects of tricyclic antidepressants on the respiratory system, we find few ones about the selective serotonin-reuptake inhibitors, particularly fluoxetine (Prozac®). Their main clinical indication are depression, panic syndrom and anxiety. Among the fluoxetine’s published reports we should mention hypersensitivity pneumonitis, phospholipidosis and interstitial lung disease.The purpose of this project is to investigate the fluoxetine treatment action on respiratory tract, concerning to the mechanics and histhopathological answer to the injury, more specifically over the pulmonary interstitium, using an experimental model in guinea-pigs...

Inhibition of tryptophan-pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats

To investigate in-vitro as well as in-vivo effects of various doses of fluoxetine [SSRI] on tryptophan metabolism in rats. Design: A pre-clinical study. Place and Duration of Study: Clinical Biochemistry Research Laboratory, Department of Biochemistry, University of Karachi. The investigation was carried out during 2000 to 2001. Subjects and Male Wistar rats [150-200 g body wt] were selected and divided into control and test groups [n = 5] for comparison. In in-vitro [10 - 1000mM] as well in-vivo [0.5 ' 30 mg/kg body wt.] studies, fluoxetine showed a statistically significant inhibition of rat liver tryptophan pyrrolase [tryptophan-2,3-dioxygenase; EC 1.13.11.11] activity. Significant increases were noted at 10 and 30 mg/kg doses in brain, serum [total and free] and liver L-tryptophan concentrations. Similarly, serum non-estrified free fatty acids showed a significant increase at both doses. There was no effect on serum glucose and albumin concentrations. It is suggested that major mechanism of action of fluoxetine is that of elevating brain tryptophan concentration and hence 5-HT synthesis by increasing the availability of circulating tryptophan to the brain secondarily to inhibition of major tryptophan degrading enzyme, hepatic tryptophan pyrrolase. It is assumed that fluoxetine inhibits the binding of apoenzyme form of tryptophan pyrrolase with its cofactor haem. The results are discussed in relation to possible involvement of disturbed hepatic tryptophan metabolism in depressive illness

Efecto de la fluoxetina sobre la insulino resistencia en pacientes obesos no diabéticos / Effects of fluoxetine on insulin resistance in non diabetic patients

Fluoxetine, a serotonin re-uptake inhibitor with antidepressive and appetite reduction effects, could improve insulin sensitivity. The aim of this work was to assess this effect of fluoxetine in obese subjects. We studied 12 subjects with a body mass index over 30, with normal oral glucose tolerance test and not subjected to dietary restrictions. Insulin sensitivity using Bergman's minimal model, sex hormone binding globulin (SHBG) and insulin like growth factor binding protein 1 (BP 1) were evaluated before and after three weeks of treatment with 60 mg OD of fluoxetine. During treatment, subjects lost a mean of 1.9 kg. When compared with basal values, insulin sensitivity index (S1) improved significantly at the end of threatment (1.71ñ0.44 and 2.72ñ0.63 respectively), SHBG increased (28.9ñ5.1 and 18.2ñ3.4 nM/ml respectively) and BP 1 did not change (2.8ñ0.9 and 1.5ñ0.3 ng/ml respectively). The changes in insulin sensitivity did not correlate with weight changes (r=0.4 NS). Weight or insulin sensitivity changes did not correlate with initial degree of insulin resistance. We conclude that the improvement in insulin sensitivity elicited by fluoxetine is not related to weight changes and may be useful in the treatment of insulin resistant obese subjects

Fluoxetina: uma breve revisäo / Fluoxetine: a brief review

Os autores fazem uma revisäo sobre os conceitos atuais, histórico, características farmacológicas e aplicações clínicas da fluoxetina

Treatment of post withdrawal depressive symptoms in detoxified heroin addicts with fluoxetine and naltrexone maintenance

Depression is a common phenomenon which might lead to early relapse in the first few weeks after opiate detoxification. There is strong evidence that depression is related to the central nervous serotonin system. To prove the hypothesis of the impact of serotonin in depressive detoxified addicts, a selective serotonin re-uptake inhibitor in the after care was used. In a prospective, open clinical trial, forty detoxified opiate addict males were randomly assigned to two groups receiving either 50mg naltrexone alone or with fluoxetine 20mg. After 30 days, the depression score was significantly lower in the floxetine group, but the incidence of continued opiate intake remained higher in this group. However, the additional naloxone provocation test did not lead to withdrawal signs, proving the naltrexone maintenance