Pharmatherapeutica最新文献

Sixty elderly patients suffering from initial mental deterioration (less than 6 months) were divided at random into two groups, homogeneous for age, sex and life habits. For 28 weeks Group I was given a placebo and Group II was given 400 mg pentoxifylline ('Trental' 400) 3-times daily for two 3-month periods interrupted by a 4-week wash-out period. Neuropsychological performance and haemorheological parameters were evaluated at the beginning and at the end of each phase of the study. The results showed that pentoxifylline medication significantly improved the psycho-intellectual performance, decreased whole blood viscosity and increased red cell filterability. The results indicate a need to concentrate further study on haemorheological factors in the clinical aspects of the ageing brain, also with a view to allowing for sufficiently long treatment periods.

An open, non-comparative study was carried out by four general practitioners into the efficacy and tolerability of a new antifungal preparation, bifonazole 1% gel. The preparation was used once daily to treat clinically diagnosed, superficial dermatophytoses and erythrasma of the feet or groin in 91 patients of which 51 were confirmed by mycological examination. A complete mycological evaluation was available for 28 patients and a cure was recorded in 23 (89%) of these cases. Four patients reported discomfort and burning on application of the preparation and changed to alternative treatments.

A total of 192 patients suffering from mild to moderate depression, with or without anxiety, accompanied by one or more specific somatic symptoms, was entered into a double-blind, multi-centre trial to compare flupenthixol and diazepam as treatments for psychosomatic syndromes in general practice. Each patient was treated for 4 weeks and assessed after 1, 2 and 4 weeks on the Hamilton Depression Scale, with visual analogue scales of depression and somatic symptoms, by global assessments (psychological and somatic symptoms) and on a side-effects scale. The principal somatic symptoms were tension headache (69 patients), epigastric discomfort (59 patients), chest pain (39 patients) and backache (25 patients). There were 9 drop-outs (2 on flupenthixol and 7 on diazepam), of whom 5 (2 on flupenthixol and 3 on diazepam) who were treated for at least 2 weeks were included in the analysis of results. All patients received 1 tablet a day (0.5 mg flupenthixol or 2.5 mg diazepam) for the first week. Thereafter, all except 5 patients (3 on flupenthixol and 2 on diazepam) had their dose doubled for the remaining 3 weeks of study. Both drugs were effective in producing consistent improvement in all four somatic symptom groups in terms of both depression and somatic symptoms over the 4 weeks of study. There was a trend throughout in favour of flupenthixol as the more therapeutically effective. Flupenthixol was significantly more effective in relieving depressive symptoms and somatic symptoms in all four somatic symptom groups considered together. It was also superior to diazepam as measured by its effect on the depression sub-scales, anxiety, agitated depression, retarded depression and melancholia. Both drugs were well tolerated, although diazepam-treated patients showed a moderate increase in side-effects scores initially, while the scores in patients treated with flupenthixol decreased consistently over all 4 weeks of the trial. It is concluded from this study that flupenthixol has an important place in the management of patients with psychosomatic illness.

A study was undertaken to investigate the possible interaction between pentoxifylline and coumarin. Ten patients on a previously stable anticoagulant treatment were investigated twice prior to, then 13 and 27 days after initiation of treatment with 1600 mg pentoxifylline daily. Coumarin therapy was continued in unaltered dosage. Parameters recorded were: bleeding time, platelet count, platelet adhesivity, spontaneous and collagen-induced platelet aggregation, activated partial thromboplastin time, prothrombin time, prothrombin-proconvertin activity, plasminogen activator and fibrin(ogen) degradation products. Platelet aggregation studies revealed a slightly higher sensitivity to collagen in 2 patients compared to pre-treatment values and in 1 patient the tendency to spontaneous aggregation was slightly increased after treatment. No other single test result changed significantly from premedication baseline values.

A double-blind, parallel group study was carried out in 51 mild to moderately depressed hospital out-patients to assess the therapeutic efficacy and side-effects of once-daily flupenthixol (1 mg) administered in the morning compared with once-daily mianserin (30 mg) administered in the evening. Patients were treated over a period of 6 weeks and assessments were made before and during treatment using the Newcastle Rating Scale, the Clinical Global Impression, the Hamilton Depression Scale, the Leeds Self-Rating Scale for Depression, and a check-list of side-effects. The results showed that 91% of flupenthixol patients and 80% of mianserin patients were assessed as 'normal' on completion of the study period. Depressive symptoms decreased progressively in both groups. Reports of side-effects in both groups showed a progressive reduction in number and severity during the study. The reduction at the end of the first week of treatment with mianserin was not as great as that seen with flupenthixol; reports of drowsiness accounted for most of the difference.

Diphenpyramide is a non-steroidal anti-inflammatory compound which has no free ionizable or particularly reactive groups, in contrast to conventional non-steroidal anti-inflammatory agents. In animal tests, diphenpyramide showed anti-inflammatory action as powerful as that of indomethacin or phenylbutazone, with major peripheral analgesic, antipyretic and uricosuric properties. The therapeutic index was more favourable than that of the reference compounds. Diphenpyramide inhibits the synthesis of inflammatory prostaglandins and antagonizes the mediators of inflammation, but does not affect platelet aggregation or blood clotting. The major biotransformation products are biphenylacetate (BPA), which is pharmacologically active, p-hydroxy-biphenylacetate (p-HBPA) and alpha-aminopyridine (AP). The first is metabolized to p-HBPA which is excreted in the urine. The serum levels of the parent drug and BPA do not result in particularly elevated peaks. Elimination occurs mostly through the faeces. The anti-inflammatory action of diphenpyramide has been extensively proven in clinical trials in which patients with various inflammatory conditions, mainly of a musculoskeletal nature, were treated. The overall therapeutic efficacy was over 80% with a high proportion in osteoarthritis. In double-blind studies, the efficacy of diphenpyramide was significantly better than that of acetylsalicylic acid or indomethacin in osteoarthritis, and comparable with that of naproxen. The preferred dose of diphenpyramide in adults was 1000 mg/day in 2 divided doses for a period of about 30 days. The effective and safe dose in children was 13 to 33 mg/day. Side-effects were seldom reported (2.5%), were mild and transient and mainly of a gastro-intestinal nature. Specific tests on possible drug influence on the gastric mucosa showed diphenpyramide to be 'gastrosafe' both on short-term, high-dose as well as on long-term standard treatments. Biopsy and endoscopy of the mucosa failed to indicate any impairment; occult blood in stools could not be detected. Diphenpyramide seems, therefore, to be an anti-inflammatory drug that combines efficacy and tolerance in the treatment of a wide variety of inflammatory musculoskeletal disorders of primary of secondary nature, as well as the associated pain. Clinical observations also suggest that diphenpyramide could safely be administered to susceptible patients, such as children and infants or elderly, in need of effective anti-inflammatory treatment.

The clinical efficacy of terconazole (triaconazole), a new triazole ketal structurally similar to ketoconazole, was evaluated in a single-blind, randomized comparative clinical trial including 60 patients with symptoms and clinical signs of vulvovaginal candidosis confirmed by microscopic examination and positive culture for Candida albicans. Three comparable groups were treated with 200 mg clotrimazole or 80 mg terconazole vaginal tablets once daily for 3 consecutive days, or one 240 mg terconazole vaginal tablet followed by 2 identical placebo pessaries. No differences in relief and initial symptomatic cure according to patient recordings on diary cards were demonstrated between the three regimens. Cure rates were 90% or more in all treatment groups 1 week after completion of therapy. At the second follow-up visit 3 weeks later, a significantly higher mycological cure rate (94%), due to significantly better therapeutic response in patients with recurrent vulvovaginal candidosis, was recorded after 3-day therapy with terconazole, while the mycological cure rates after clotrimazole and single-dose terconazole treatment only were 65% and 55%, respectively. It was concluded that terconazole represents an efficient and well-tolerated therapeutic alternative in the topical treatment of vulvovaginal candidosis.

A double-blind crossover study, with placebo periods preceding each active treatment, was carried out in 29 patients with ischaemic heart disease to compare the clinical efficacy of isosorbide 5-mononitrate 40 mg twice daily and the same regimen of sustained-release isosorbide dinitrate. Assessment was by bicycle ergometry, symptomatology and blood nitrate level measurements. After 2-weeks' therapy with isosorbide 5-mononitrate, mean ST segment depression at the highest comparable exercise level for each patient was reduced by 32.5% (p less than 0.01), the mean maximum exercise level was increased from 87 to 102 Watts (17.8%, p less than 0.01), and mean work capacity was increased from 581 Watts-minutes to 783 Watts-minutes (34.6%, p less than 0.01). With sustained-release isosorbide dinitrate, ST segment depression was reduced by 16.5% (p less than 0.05); maximum exercise level showed only a small non-significant increase, from 89 to 97 Watts (8.6%), but work capacity increased (p less than 0.05) from 593 Watts-minutes to 705 Watts-minutes (18.9%). There was no significant difference between drugs as regards ST segment reduction but a slight difference in favour of isosorbide 5-mononitrate (p less than 0.05) in terms of maximal exercise level and work capacity. Both drugs resulted in very small reductions in blood pressure (p less than 0.001 for systolic with isosorbide 5-mononitrate; p less than 0.01 for systolic and p less than 0.05 for diastolic with sustained-release isosorbide dinitrate). Heart rate and rate-pressure product changed little with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

An open, crossover study lasting 8 weeks was performed to establish if a twice daily regimen of combined inhalation of salbutamol and beclomethasone dipropionate from a single inhaler was as effective in controlling asthma as the 4-times daily regimen. The results from these two treatment periods were compared with an initial 4-week baseline period when all patients received the same agents from separate inhalers on a 4-times daily dose schedule. Twenty stable asthmatics were entered into the study and 19 completed the three treatment periods. The clinic lung function data, symptomatic inhaler usage, requests for additional therapy and physician's subjective assessment of treatment showed that all three treatment regimens were similarly effective in managing the patients' asthma. There was no significant difference between the mean PEFR measurements taken 4 times each day between the two treatment regimens of the combination inhaler. However, except for PEFR in the afternoon, the mean values for both treatment schedules of the combination inhaler were significantly greater (p less than 0.05) than those during the separate inhaler baseline period. More than half the patients considered that both treatment schedules of the combination inhaler provided better control of their asthma than treatment with the separate inhalers, and the majority preferred the twice daily regimen to the 4-times daily regimen. The results, overall, showed that in stable asthmatics the combined administration of salbutamol and beclomethasone dipropionate from one inhaler provides significantly better therapy than the same agents from separate inhalers and that the twice daily dose schedule of the combination inhaler is equally as effective as a 4-times daily regimen.

The acute effects of a single 10 micrograms dose of a new dopamine agonist, pergolide, were investigated in 6 healthy women and 6 women with cyclical oedema. There was a prompt and significant reduction in mean plasma prolactin concentrations with maximum suppression occurring at 4 hours in both groups. However, the prolactin suppression was significantly less in the women with cyclical oedema. This is further evidence for a prolactin disturbance in cyclical oedema, and consistent with the proposal that reduced dopaminergic tone may be an important abnormality in the disorder.