RESUMO
BACKGROUND: Peripheral arterial disease affects five per cent of men and women by late middle age. Approximately 25% of those affected will develop critical limb ischaemia (rest pain, ulceration and gangrene) within five years. Naftidrofuryl is a vasoactive drug which may be beneficial in the treatment of critical limb ischaemia. OBJECTIVES: To determine whether naftidrofuryl, when administered intravenously, is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2012) and CENTRAL (2012, Issue 4). We searched the reference lists of articles. We also contacted pharmaceutical companies for any unpublished trials. SELECTION CRITERIA: All randomised controlled trials of critical limb ischaemia in which participants were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. People with intermittent claudication were not included. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified, but eight were excluded because of poor methodology. The eight included trials involved a total of 269 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and mean differences were estimated where appropriate. MAIN RESULTS: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (mean difference (MD): 0.42; 95% confidence interval (CI)1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also non-significant. The effect on mean ankle systolic pressure was inconclusive. AUTHORS' CONCLUSIONS: Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.
Assuntos
Extremidades/irrigação sanguínea , Isquemia/tratamento farmacológico , Nafronil/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Vasodilatadores/uso terapêutico , Amputação Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Infusões Intravenosas , Masculino , Nafronil/administração & dosagem , Dor/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasodilatadores/administração & dosagemRESUMO
Two groups of tinnitus patients (n=93) were recruited, one of which was treated with standard infusion therapy and further acute medical intervention, while the other obtained an additional psychotherapeutic intervention. Questionnaires and interviews were taken at beginning of the treatment, and 9 days and 3 years after treatment. The accompanying psychotherapeutic intervention consisted primarily of client-centered counseling, guided relaxation techniques from clinical hypnosis, and some standard and tinnitus-related methods for a better coping with stress. After 9 days, both treatment groups showed significant improvement in several psychological characteristics. However, there was no evidence for the superiority of the combined treatment with psychological intervention. Psychotherapeutic treatment accompanying the acute medical treatment probably shows better effectiveness in an ambulant setting with both patients and medical healthcare professionals rating it as 'very helpful'. This pilot study has contributed initial results for the integrated treatment of the acute tinnitus and has helped in the development of further therapeutic strategies as well as an evidence based concept for further evaluation. This study received one of the two scientific first prizes of the "German Tinnitus League".
Assuntos
Derivados de Hidroxietil Amido/administração & dosagem , Nafronil/administração & dosagem , Pentoxifilina/administração & dosagem , Psicoterapia , Transtornos Somatoformes/terapia , Zumbido/terapia , Vasodilatadores/administração & dosagem , Adaptação Psicológica , Adulto , Terapia Cognitivo-Comportamental , Terapia Combinada , Cortisona/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Psicoterapia Centrada na Pessoa , Inventário de Personalidade , Terapia de Relaxamento , Papel do Doente , Transtornos Somatoformes/psicologia , Inquéritos e Questionários , Zumbido/psicologiaRESUMO
Naftidrofuryl (CAS 31329-57-4) is used, mainly in elderly patients, in the treatment of various vascular disorders. The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in caucasian male and female subjects with renal impairment versus healthy volunteers. This prospective and open study was conducted in three parallel groups: Group A = healthy subjects with a Cl(CR) > 80 ml/min, Group B = uraemic patients with a 20 < or = Cl(CR) < 40 ml/min, Group C = uraemic patients with a Cl(CR) < 20 ml/min. Blood samples were taken over a period of 32 h after dosing. The mean values (+/-SD) of the pharmacokinetic parameters of naftidrofuryl for group A were as follows: tmax: 1.3 h (median), Cmax: 174 +/- 46 ng/ml, t(1/2 beta): 4.4 +/- 1.1 h, AUC(0-infinity): 1541 +/- 384 ng x h/ml; for group B: tmax: 2.5 h (median), Cmax: 239 +/- 94 ng/ml, t(1/2 beta): 5.0 +/- 1.2 h, AUC(0-infinity): 2361 +/- 751 ng x h/ml; for group C: tmax: 3.0 h (median), Cmax: 236 +/- 104 ng/ml, t(1/2 beta): 5.0 +/- 2.1 h, AUC(0-infinity): 2488 +/- 2003 ng x h/ml. The statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each group. No significant difference between each group was observed. In conclusion, renal insufficiency did not appear to influence the pharmacokinetic profile of oral naftidrofuryl.
Assuntos
Nefropatias/metabolismo , Nafronil/farmacocinética , Antagonistas da Serotonina/farmacocinética , Adulto , Cromatografia Líquida de Alta Pressão , Creatinina/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Nafronil/administração & dosagem , Nafronil/efeitos adversos , Estudos Prospectivos , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/efeitos adversos , Comprimidos , Uremia/metabolismoRESUMO
BACKGROUND: Testicular cancer has a favorable prognosis in the majority of patients due to the excellent susceptibility to chemotherapy with cisplatin, etoposide and bleomycin (BEP), which is commonly administered over 3-4 cycles of treatment. CASE REPORT: A 22-year-old male failed to achieve complete response after unconventional treatment with 6 courses of BEP for intermediate-risk metastasized testicular cancer. The patient developed chemotherapy-induced digital necrosis and substantial loss of digital function after this excessive treatment. This condition resolved with infusional alprostadil combined with oral clonidin and pentoxifyllin. RESULT: Infusional alprostadil adds substantial clinical benefit to combined vasoactive therapy in chemotherapy-induced vascular toxicity, even after the onset of digital necrosis.
Assuntos
Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Dedos/patologia , Doença de Raynaud/tratamento farmacológico , Doença de Raynaud/etiologia , Neoplasias Testiculares/tratamento farmacológico , Vasodilatadores/administração & dosagem , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Clonidina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Masculino , Nafronil/administração & dosagem , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Falha de Tratamento , Resultado do TratamentoRESUMO
In the present study, we investigated the effects of a single and a repeated (5 days) administration of naftidrofuryl, a serotonin 5-HT2 receptor inhibitor having neuroprotective properties, on functional brain physiology in male healthy elderly subjects, using quantitative electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twelve subjects aged 60 +/- 3.8 years completed the quantitative EEG study, where the effects of 400 and 600 mg were assessed, and 12 other subjects (aged 56 +/- 4.7 years) completed the fMRI study, where the effect of 400 mg was assessed on the brain activation induced by the continuous performance test (CPT). Naftidrofuryl induced a transient reduction in alpha activity followed by a specific synchronisation of the 9.5- to 11-Hz EEG activity most pronounced after repeated administration. Such regimen also increased the CPT-induced brain activation visualized by way of fMRI. The results of the present study can be interpreted at the functional level that naftidrofuryl induced an improved level of vigilance or an increased capacity of alertness in healthy elderly subjects.
Assuntos
Encéfalo/efeitos dos fármacos , Nafronil/farmacologia , Antagonistas da Serotonina/farmacologia , Encéfalo/fisiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nafronil/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Antagonistas da Serotonina/administração & dosagemRESUMO
Enzymatic retinyl ester hydrolysis is a key reaction for maintaining cellular retinol homeostasis. The ability of naftidrofuryl and erythromycin to inhibit retinol liberation by retinyl ester hydrolase (REH) in vitro suggests an ability to interfere with vitamin A metabolism in vivo, particularly during hepatic processing. To address this question, systemic and local response to these agents were studied in Brown Norway (BN) and Long-Evans (LE) rats. The study was conducted in two parts: a drug-loading phase and a washout phase. Analysis of variance of the time course changes in plasma retinol during the post-treatment period (Days 10-18) showed rat strain (p < 0.04) and time (p < 0.001; strain-by-time interactive effect, p < 0.001) to be significant factors, but drug exposure (p = 0.19) was not significant. Endpoints included hepatic REH activity, size and composition of the liver vitamin A stores, and retinoid content of the kidneys. Rats recovering from naftidrofuryl dosing demonstrated a lower REH activity than did animals recovering from erythromycin treatment (p < 0.009). The major side effect of erythromycin is vitamin A accumulation in the liver (p < 0.001) and reductions in retinol reserves (p < 0.02) were among the consequences of naftidrofuryl treatment. In the kidney of LE rats, there were higher concentrations of vitamin A (p < 0.003) secondary to naftidrofuryl exposure. Together our data suggest that clinically achievable concentrations of the drugs, given as a continuous infusion, produce aberrations in vitamin A metabolism.
Assuntos
Hidrolases de Éster Carboxílico/antagonistas & inibidores , Eritromicina/farmacologia , Fígado/metabolismo , Nafronil/farmacologia , Vitamina A/metabolismo , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Hidrolases de Éster Carboxílico/metabolismo , Eritromicina/administração & dosagem , Infusões Intravenosas , Infusões Parenterais , Rim/metabolismo , Cinética , Fígado/enzimologia , Masculino , Nafronil/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Endogâmicos BN , Ratos Long-Evans , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologia , Vitamina A/sangue , Deficiência de Vitamina A/induzido quimicamenteRESUMO
BACKGROUND: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. PATIENTS AND METHODS: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values. RESULTS: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.
Assuntos
Claudicação Intermitente/tratamento farmacológico , Nafronil/administração & dosagem , Qualidade de Vida , Vasodilatadores/administração & dosagem , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nafronil/efeitos adversos , Estudos Prospectivos , Vasodilatadores/efeitos adversosRESUMO
PURPOSE: To evaluate the effects of an S2 specific antiserotonine agent (Naftidrofuryl) on the optic nerve head blood flow in glaucomatous patient. PATIENTS AND METHOD: 11 glaucomatous subjects were enrolled in the study. After administration of 200 mg naftidrofuryl twice daily for 7 days: values of optic nerve head blood flow (Fonh), velocity and volume were recorded in the temporal rim and cup of the optic nerve head. Blood flow measurements were performed by laser doppler flow-metry at day 0 and day 7 before and one and two hours after drug administration. RESULTS: Our study showed a significant improvement of perfusion pressure (p = 0.02) at day 7 and an increase of mean ophthalmique artery pressure (p = 0.03). DISCUSSION: Our preliminary results on a small number of patients and a short follow-up indicate that the use of naftidrofuryl may enhance optic nerve head blood flow in glaucomatous patients. Further studies may confirm these results.
Assuntos
Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma/tratamento farmacológico , Nafronil/administração & dosagem , Disco Óptico/irrigação sanguínea , Antagonistas da Serotonina/administração & dosagem , Vasodilatadores/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Glaucoma/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Nafronil/efeitos adversos , Antagonistas da Serotonina/efeitos adversos , Vasodilatadores/efeitos adversosRESUMO
BACKGROUND: Hearing loss resulting from exposure to permanent or repeated amplified music in professional musicians and music consumers is described in literature. The risk of hearing loss does not exist only after prolonged exposure to music. Short-term exposure to very high sound levels, for example in concerts, can also cause hearing loss and tinnitus. PATIENTS: The retrospective study includes 24 patients who required rheologic therapy between 1994 and 1997 due to a music related acoustic trauma. The type, intensity, and length of music exposure as well as the distance and the position to the source of noise were examined. The type of hearing damage and its development during rheological treatment was studied by pure-tone audiometry. RESULTS: In the majority of examined patients (67%) the hearing loss developed on the basis of one-time exposure at a rock concert or pop concert, followed by hearing loss from attending discotheques (17%) or parties (12%), and music exposure from personal cassette players (4%). The majority of patients showed a maximum hearing loss of 40-60 dB (A) in a frequency between 3 kHz and 4 kHz. Pure-tone audiometry in 58% of the patients exhibited a unilateral threshold in a frequency between 3 kHz and 4 kHz combined with ipsilateral tinnitus of the same frequency. Twenty-one percent of the patients showed a symmetric bilateral threshold and tinnitus between 3 kHz and 4 kHz. In 8% there was a unilateral tinnitus, and in 13% a bilateral tinnitus without any hearing loss. All patients improved their hearing loss during rheologic treatment. Improvement in the tinnitus was only achieved in 33% of the examined cases. CONCLUSION: The risk of permanent hearing loss resulting from short-term exposure to amplified music is low compared to the risk of continuous tinnitus. Given the lack of acceptance of personal ear protectors, the risk of acute hearing damage due to amplified music could be reduced by avoiding the immediate proximity to the speakers.
Assuntos
Perda Auditiva Provocada por Ruído/etiologia , Música , Zumbido/etiologia , Doença Aguda , Adolescente , Adulto , Audiometria de Tons Puros , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Humanos , Infusões Intravenosas , Masculino , Nafronil/administração & dosagem , Pentoxifilina/administração & dosagem , Piracetam/administração & dosagem , Prognóstico , Estudos Retrospectivos , Espectrografia do Som , Zumbido/tratamento farmacológico , Vasodilatadores/administração & dosagemRESUMO
The present study was devised to determine whether the pattern of hearing loss has any meaning for prognosis in patients with sudden hearing loss. The audiograms and clinical records of 145 patients with sudden deafness between 1991 and 1993 were reviewed. Forty-eight of the patients were females and 97 were males. All patients had been hospitalized and treated with intravenous infusions of naftidrofuryl. The best recovery rate was seen in patients with low-tone hearing losses (68.8% complete and 25% partial recoveries), whereas in patients with high-tone and flat losses the recovery rates were 41.9% and 45.5% respectively for complete recovery and 52.4% and 36.3% for incomplete recovery. The entire group showed an overall recovery rate of 52.4% for complete recovery and 30.3% for incomplete recovery. Immediate treatment resulted in a positive effect on prognosis. Patients under 30 years of age had a somewhat better recovery rate than did older patients. Pre-existing risk factors (diabetes, hypertension, etc.) or accompanying symptoms of vestibular disturbances did not influence prognosis, whereas patients with pre-existing inner ear deafness or with a recurrence of sudden deafness showed relatively lower recovery rates. The possible reasons responsible for exceptionally good prognosis of low-tone hearing losses are discussed.
Assuntos
Perda Auditiva Súbita/etiologia , Adulto , Idoso , Audiometria de Tons Puros , Limiar Auditivo/efeitos dos fármacos , Diagnóstico Diferencial , Feminino , Perda Auditiva Súbita/tratamento farmacológico , Humanos , Infusões Intravenosas , Masculino , Doença de Meniere/etiologia , Pessoa de Meia-Idade , Nafronil/administração & dosagem , Prognóstico , Vasodilatadores/administração & dosagem , Testes de Função VestibularRESUMO
Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.
Assuntos
Oxalato de Cálcio/urina , Cálculos Renais/induzido quimicamente , Nafronil/efeitos adversos , Vasodilatadores/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Cristalização , Relação Dose-Resposta a Droga , Feminino , Avaliação Geriátrica , Humanos , Cálculos Renais/urina , Masculino , Nafronil/administração & dosagem , Vasodilatadores/administração & dosagemRESUMO
We investigated the action of oral naftidrofuryl, a serotonin (5-HT2)antagonist, on atheromatous plaque formation, endothelial function, and neutrophil activity in cholesterol-fed (1% for 12 weeks) rabbits. Cholesterol feeding caused almost complete (84 +/- 4%) coverage of the aortic surface with atheromas and a marked intimal thickening. The endothelium-dependent relaxation to acetylcholine (ACh 1 nM-10 microM) and substance P (30 nM) was considerably reduced, whereas the relaxing effect to the endothelium-independent nitric oxide donor linsidomine (SIN-1) (100 microM) was unchanged. Treatment of hypercholesterolemic rabbits with naftidrofuryl (50 mg/kg body weight) resulted in a marked (54 +/- 6%, p < 0.05) reduction in aortic plaque formation. Endothelium-dependent relaxation to ACh was significantly improved in rings of both thoracic aorta: 33 +/- 5 versus 14 +/- 5% (p < 0.05) and abdominal aorta 68 +/- 9 versus 37 +/- 10% (p < 0.05). Similar results were obtained with substance P, but the responses to SIN-1 were unchanged. Zymosan-induced, luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMN) was markedly stimulated in cholesterol-fed rabbits. Naftidrofuryl reduced this hyperreactivity to that of control rabbits. There was no change by naftidrofuryl in any of these parameters in control rabbits, precluding a direct action of the compound in nonhypercholesterolemic conditions. These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation.
Assuntos
Arteriosclerose/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Nafronil/uso terapêutico , Neutrófilos/efeitos dos fármacos , Acetilcolina/farmacologia , Administração Oral , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/patologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/patologia , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Modelos Animais de Doenças , Endotélio Vascular/patologia , Fibrinogênio/metabolismo , Medições Luminescentes , Luminol/farmacologia , Masculino , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Nafronil/administração & dosagem , Nafronil/farmacologia , Neutrófilos/fisiologia , Óxido Nítrico/metabolismo , Coelhos , Distribuição Aleatória , Substância P/farmacologia , Vasodilatadores/farmacologia , Zimosan/farmacologiaRESUMO
We report two cases of acute renal failure in patients with arteriosclerosis obliterans treated by intravenous infusion of naftidrofuryl oxalate. At renal biopsy the histological lesions were identical with those found in ARF due to hyperoxaluria of other causes, revealing tubular epithelial necrosis and massive intratubular precipitation of calcium oxalate monohydrate (C1) crystals. A second study was then conducted in four other patients with arteriosclerosis obliterans to evaluate serum and urinary levels of oxalate, and crystalluria during the intravenous administration of 800 mg of naftidrofuryl oxalate per day for 10 days. During the course of treatment, the serum and urinary oxalate levels were found to increase substantially, with the gradual onset of massive C1 crystalluria. These results indicate that naftidrofuryl oxalate was responsible for the acute renal failure in the first two patients. High intravenous doses of naftidrofuryl oxalate must be used cautiously, with close surveillance of renal function.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Rim/efeitos dos fármacos , Nafronil/administração & dosagem , Nafronil/efeitos adversos , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Arteriosclerose Obliterante/tratamento farmacológico , Oxalato de Cálcio/química , Oxalato de Cálcio/urina , Cristalização , Humanos , Infusões Intravenosas , Rim/patologia , Masculino , Pessoa de Meia-Idade , Oxalatos/sangue , Oxalatos/urina , Ácido OxálicoAssuntos
Injúria Renal Aguda/induzido quimicamente , Transplante de Rim , Nafronil/efeitos adversos , Vasodilatadores/efeitos adversos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Adulto , Oxalato de Cálcio/química , Oxalato de Cálcio/metabolismo , Cristalização , Overdose de Drogas , Feminino , Humanos , Infusões Intravenosas , Nafronil/administração & dosagem , Doenças Vasculares Periféricas/tratamento farmacológico , Vasodilatadores/administração & dosagemRESUMO
Naftidrofuryl is commonly used in treatment of peripheral vascular disease. Its vasodilator action has been partly explained by its inhibitory effect of 5-HT2 receptors on peripheral arteries in vitro. The purpose of this study was to test in vivo whether naftidrofuryl selectively inhibits 5-hydroxytryptamine (5-HT)-mediated constriction of large arterioles in the peripheral microcirculation. This constriction appears to be 5-HT2 receptor-mediated. Three separate protocols were used to test the effects of naftidrofuryl: chronic injection (15 mg/kg, i.p., twice daily for 5-6 days; n = 7), acute intravenous (i.v.) infusion (15 mg/kg over 30 min; n = 7), or topical application (5 x 10(-8) M, n = 6; 5 x 10(-7) M, n = 5; 5 x 10(-6) M, n = 5; 10(-5) M, n = 7). Male Sprague-Dawley rats (145-185 g body weight) were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was prepared for intravital video microscopy. Diameter response of arterioles (70-120 microns) to increasing concentrations of locally applied 5-HT (10(-8)-10(-4) M) was assessed. In rats receiving no drug treatment, 5-HT caused vasoconstriction of arterioles beginning at 10(-6) M and reaching approximately 40% constriction at 10(-4) M. These vasoactive responses were not altered by chronic daily doses or an acute infusion of naftidrofuryl. 5-HT responses obtained with and without naftidrofuryl applied directly into the cremaster-bath also had little effect on the arteriole response at each of the four concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Nafronil/farmacologia , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Técnicas In Vitro , Ketanserina/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , Músculos/irrigação sanguínea , Nafronil/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/efeitos dos fármacosRESUMO
80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.
Assuntos
Flavonoides/administração & dosagem , Perda Auditiva Súbita/tratamento farmacológico , Derivados de Hidroxietil Amido/administração & dosagem , Nafronil/administração & dosagem , Extratos Vegetais , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Flavonoides/efeitos adversos , Ginkgo biloba , Perda Auditiva Súbita/etiologia , Humanos , Derivados de Hidroxietil Amido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nafronil/efeitos adversos , Zumbido/tratamento farmacológico , Zumbido/etiologiaRESUMO
The aim of the present study was to investigate the influence of long term intravenous administration of naftidrofuryl (Dusodril-Lipha Arzn) twice daily in a dose of 200 mg in continuous, 4-hour infusion in 500 ml 0.9% NaCl to the patients suffering from a peripheral arterial occlusive disease (PAOD) in a clinical condition with special attention paid to transcutaneous partial oxygen pressure measurements (tcPO2) and rheographic parameters. Also the effect of treatment with naftidrofuryl on the platelet adhesion to the bovine extracellular matrix, the leukocyte adhesion to nylon fibres, and the number of platelet-leukocyte aggregates has been studied. We have found that after the naftidrofuryl treatment tcPO2 significantly increased from 38.5 +/- 0.8 mm Hg to 54.6 +/- 11.5 mm Hg, and the impedance plethysmography indexes, such as the height of the rheographic wave, the area of the rheographic wave and the rheographic index were also slightly increased. The leukocyte adherence to nylon fibres, the platelet adhesion to the extracellular matrix and the total number of platelet-leukocyte aggregates were significantly reduced after the treatment with Dusodril. On the basis of this study it seems that the observed influence of naftidrofuryl on leukocyte function in patients with PAOD is an additional mode of action of this drug that can be of new clinical value in the treatment of patients with a peripheral occlusive arterial disease. It seems that tcPO2 measurements in ischaemic legs can be recommended as a very sensitive method of monitoring the efficacy of vasoactive drugs in patients with PAOD.
Assuntos
Arteriopatias Oclusivas/tratamento farmacológico , Monitorização Transcutânea dos Gases Sanguíneos , Nafronil/uso terapêutico , Adulto , Idoso , Animais , Arteriopatias Oclusivas/sangue , Bovinos , Matriz Extracelular/metabolismo , Feminino , Humanos , Infusões Intravenosas , Teste de Inibição de Aderência Leucocítica , Masculino , Pessoa de Meia-Idade , Nafronil/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Pletismografia , Pletismografia de ImpedânciaRESUMO
The case of a 7-year-old boy who suffered a convulsion during parenteral infusion of naftidrofuryl is reported. The effectiveness of adding naftidrofuryl to infusions designed to increase cochlear blood flow in cases of sudden hearing loss has been keenly debated in the otologic literature. Several hazards are associated with this drug, especially when the infusion is performed too fast. We recommend an individual decision for each patient suffering from cochleo-vestibular disorder based on the neurological and cardiological risk factors and the therapeutic possibilities.
Assuntos
Epilepsia Tônico-Clônica/induzido quimicamente , Perda Auditiva Súbita/tratamento farmacológico , Nafronil/efeitos adversos , Limiar Auditivo/efeitos dos fármacos , Criança , Humanos , Infusões Intravenosas , Masculino , Nafronil/administração & dosagemAssuntos
Isquemia/cirurgia , Perna (Membro)/irrigação sanguínea , Nafronil/administração & dosagem , Papaverina/administração & dosagem , Resistência Vascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/cirurgia , Humanos , Injeções Intra-Arteriais , Artéria Poplítea/efeitos dos fármacos , Artéria Poplítea/cirurgiaRESUMO
Eighty patients with idiopathic sudden deafness existing no longer than 10 days were included in a prospective randomized double-blind study. Patients were treated for 10 days with infusions of either 10% low-molecular weight dextran or the combination of low-molecular weight dextran with naftidrofuryl. Before treatment and after 10 days hearing loss in the affected ear was determined at 0.5, 1, 2, 3, 4 and 6 kHz. The mean hearing loss was then calculated as the average from these values. During monotherapy with low-molecular weight dextran the mean hearing loss decreased from 40 to 27 dB compared to 38 to 17 dB when naftidrofuryl treatment was added (p < 0.01 between groups). A significant benefit of naftidrofuryl on hearing loss was also found at frequencies between 0.5 and 3 kHz. Furthermore, patients reported better improvement of tinnitus when naftidrofuryl was combined with dextran. Two patients receiving dextran alone developed side effects: one had an allergic reaction causing withdrawal of treatment, which the other case had vertigo, nausea and headache with spontaneous recovery. The results of the study showed that treatment with naftidrofuryl in addition to hemodilution with low-molecular weight dextran was of therapeutic benefit in the therapy of sudden deafness without increasing the rate of side effects.