Pharmatherapeutica最新文献

One hundred and sixteen mentally handicapped patients with behavioural disorders were studied in a double-blind clinical comparison of zuclopenthixol decanoate injection (mean dosage 123 mg/week) and placebo. The study consisted of a 4-week open phase, in which all patients were treated with zuclopenthixol decanoate, followed by a 12-week double-blind phase where approximately half of the patients were changed to placebo. Patients were assessed every 2 weeks using the Clinical Global Impression, the Nurse's Observation Scale for In-patient Evaluation, a specific behaviour rating scale designed for this study and a side-effects check-list. Fourteen patients in the placebo group were withdrawn because of an increase in the frequency and severity of their behavioural disorders compared to only 4 in the zuclopenthixol decanoate group. Analyses of the rating scales of the patients remaining in the study also showed zuclopenthixol decanoate to be superior to placebo in the treatment of mentally handicapped patients with behavioural disorders. Side-effects in general were not a problem and did not affect treatment.

Haemorheological knowledge achieved in the past decade has revealed the essential interactions of flow properties of blood with haemostatic, coagulation, and vessel wall mechanisms in blood flow disturbances. Fine tuning of these factors maintains the physiologically adequate perfusion of the nutritive microcirculation. Under pathological conditions, therefore, the most beneficial effect can be expected from the therapeutic approaches which, apart from the disturbed flow properties of the blood itself, improve also all the other factors involved. In consequence, it is suggested that treatment of circulatory disturbances should be directed not only at the reduction of enhanced red blood cell aggregation and improvement of impaired red blood cell deformability, but also at a diminuation of enhanced platelet and white cell hyperreactivity as well as at an amendment of hypercoagulability and of the affected endothelial and vessel wall systems. Experimental and clinical studies are reviewed to show that pentoxifylline meets these different requirements to a great extent. Its multi-functional pharmacological profile suggests new aspects in the treatment of circulatory disorders in many diseases and in the prevention of thrombotic events.

A retrospective study of 107 neonates with meningitis showed that in 45% of cases the condition occurred during the first 48 hours after birth, probably following a materno-foetal infection. Male neonates accounted for 70% of the cases. In 15% of cases, the mothers previously had a known infectious disease and 55% of cases came from an unfavourable socio-economic environment. Over 50% of the infants had to be resuscitated at birth. The majority of organisms isolated were Gram-negative bacteria or Enterobacteriaceae; the commonest organism was Haemophilus influenzae. The most effective specific treatment (91% favourable results) was intravenous amoxycillin plus intramuscular gentamicin. It is recommended that the newborn infant of parents living in unfavourable socio-economic circumstances should receive careful follow-up during the first week after birth so that the diagnosis of bacterial meningitis can be made at the start of infection. The neonate should receive effective prophylactic antibiotic cover if resuscitated, if the mother has suffered from an infectious disease during pregnancy or if premature rupture of the membranes has occurred.

A study was carried out in 15 stable asthmatics and 5 patients with partially reversible airflow obstruction to compare the efficacy and tolerability of a single dose of 200 micrograms fenoterol plus 80 micrograms ipratropium bromide ('Duovent') administered either by metered dose aerosol or as a dry powder preparation for inhalation ('Inhalets'). Using a double-dummy technique, patients received each formulation, in random order, on 2 separate days within 1 week. Spirometric measurements were made over a period of 6 hours after the dose. The results showed that a 35% peak improvement in mean FEV1 occurred with each method of administration and there was no statistical difference between responses. Improvements of 25% were sustained for over 4 hours and effects on pulse rate and tremor were similar for both preparations.

A study was carried out to investigate whether diltiazem influence blood rheology, as has been reported for some other calcium channel blockers. Twenty patients with clinical, stable angina pectoris were treated with 2 x 90 mg diltiazem per day for 2 weeks. Blood viscosity, plasma viscosity, haematocrit, blood cell filterability and red cell aggregation were taken as in vitro measures quantifying the flow properties of blood. After 1-week's treatment, low and middle shear blood viscosity had declined significantly. This change was more pronounced after 2-weeks' medication. At this point, there was also an increase in blood cell filterability. All other variables did not show significant alterations. The results suggest a significant fluidification of blood during diltiazem treatment. This effect may reduce the viscous component of the total peripheral resistance, and therefore, it may contribute to an increase in perfusion and to the anti-anginal properties of the drug.

An open, multi-centre, general practice study was carried out in 80 patients with acute diarrhoea to compare the effectiveness and tolerability of treatment with a liquid formulation of smectite, a hydrated aluminium-magnesium silicate (Liquid 'Diasorb'), and loperamide. Patients were allocated at random to receive one or other treatment for a maximum of 48 hours. Thirty-three of the patients on the smectite preparation and 30 of those on loperamide had acute diarrhoea of at least 24 hours but no longer than 48 hours in duration. Patients received a daily dose of 6 to 9 g smectite or 8 to 12 mg loperamide, depending on the symptoms. Details of red and white cell counts, serum electrolyte concentrations and stool culture for pathogens and parasites were recorded on entry and after 1 week. The results, judged in terms of resolution of symptoms after 2 and 7 days, doctor and patient assessment of response to therapy, and incidence of side-effects, showed that both treatments were equally effective and well-tolerated. Two patients were withdrawn, 1 patient (Liquid 'Diasorb') because of lack of response and the other (loperamide) because of dryness of the mouth and nausea. Laboratory parameters remained unchanged apart from a slight decrease in leucocytes in both groups.

In view of the lack of published data on the oral bronchodilator preparation 'Franol' (120 mg theophylline, 11 mg ephedrine hydrochloride and 8 mg phenobarbitone per tablet) a double-blind study was carried out to compare the effects on lung function of a single dose of 2 'Franol' tablets, 1 'Franol' plus 1 placebo tablet, or 2 placebo tablets over a period of 8 hours in 30 asthmatic patients with reversible airways resistance (mean FEV1 1.31 l increasing to 1.71 l after 200 micrograms salbutamol inhalation). 'Franol' produced dose-dependent bronchodilation. Two tablets caused significant bronchodilation from 90 minutes to 8 hours (peak change from baseline at 2.5 hours: FEV1 20.8%, PEFR 22.3%). One tablet of 'Franol' produced significant bronchodilation only between 60 minutes and 3 hours (change from baseline at 2.5 hours: FEV1 7.5%, PEFR 7.9%). There was no change in lung function with placebo (change from baseline at 2.5 hours: FEV1 5.4%, PEFR 5.9%). Median serum theophylline levels at 2.5 hours were 6.38 micrograms/ml for 2 tablets and 3.18 micrograms/ml for 1 tablet. Median peak phenobarbitone levels were 0.5 micrograms/ml. There were no clinically relevant changes in pulse rate and blood pressure during the study and no adverse events were reported.

An assessment was carried out in 59 women with proven vaginal candidosis to compare the efficacy and tolerance of itraconazole used in three different treatment regimens. Patients were allocated at random to receive a single oral dose of 200 mg itraconazole for 1, 2 or 3 days. They were reassessed 1 week and 4 weeks after treatment for remission of clinical signs and symptoms and repeat mycological investigations. All three regimens yielded successful clinical results, global evaluation at 4 weeks showing complete remission in 100% (5/5), 81.5% (25/27) and 92.3% (24/26) of patients, respectively. One patient (on 2-day treatment) required alternative treatment before the 4-week assessment. Minor gastric side-effects were reported by a few patients on the 2-day and 3-day treatment regimens; these resolved spontaneously.

An open pilot study was carried out over a period of more than 2 years to assess the steroid-sparing effect of ketotifen (1 mg twice daily) in 12 steroid-dependent asthmatic patients. Daily steroid consumption (prednisolone equivalent) was calculated for the year before and for 1 and 2 years of ketotifen treatment from the total of all doses given throughout the year. Results showed that in 6 of the 12 patients who responded with reduced steroid consumption the mean daily dose decreased from 5.7 mg to 4.1 mg/day (p less than 0.05) in the first year of ketotifen: the final mean reduction rate at the end of the 2-year trail was 83.6% (p less than 0.005). Furthermore, the mean daily consumption of beta 2-stimulants (salbutamol equivalent) decreased from 8.7 to 6.2 mg/day (p less than 0.025) in the responders. In the 6 non-responders, there was a slight increase in mean daily steroid consumption from 2.4 mg to 3.0 mg/day. The most frequently reported side-effect of ketotifen was dizziness, which occurred in one-third of the patients; all patients, however, were able to continue with treatment.

Seventy-six patients with labyrinthine diseases of vascular origin were treated in a 6-week double-blind comparative study with either 400 mg pentoxifylline ('Trental') or 75 mg cinnarizine 3-times daily. Clinical evaluations, supported by audiological tests and vectornystagmography, were carried out before and after treatment. Statistical analysis of the results showed pentoxifylline to be globally superior to cinnarizine and especially to have a more intense antivertiginous effect. No significant differences were observed between the two drugs in respect of tinnitus and hearing loss therapy. Side-effects were occasional, mild and well tolerated in the pentoxifylline group, and more pronounced and frequent with cinnarizine.