Pharmatherapeutica最新文献

Oral and/or parenteral amoxycillin was used to treat 52 young and adult patients suffering from moderately severe to severe bronchitis, bronchopneumonia or acute lobar pneumonia. The mean time between onset of disease and start of treatment was 3.8 days. Patients received doses of amoxycillin ranging from 375 mg to 1 g 2 to 3-times daily depending on the severity of the condition for a mean of 6.4 days. There was complete resolution of clinical symptoms such as fever, cough and pleural pain after 3 days in all but 3 of the patients. Response was considered excellent or good in 77% of patients and satisfactory in 14%. Mild to moderate side-effects such as urticaria and nausea were reported in 8 patients but were not severe enough to interrupt treatment. Overall, amoxycillin was considered to be effective in 82% and partially so in 11% of the patients treated.

Apart from alcohol, various other substances with a psychotropic effect have been discussed recently in relation to their association with road traffic safety. There has been a general lack of hard facts, however, on how much drug use and abuse influence this. In the absence of data on the frequency of such effects, a representative random sample (approx. 8000 persons) of the Austrian population was interviewed and questioned on their drug intake. A smaller sample (2007 persons) was also questioned as to their behaviour regarding road traffic participation. The results showed that those drugs taken most frequently belong to the 'analgesic' group, whilst the frequency in use of substances to which greater importance is attached currently regarding road safety is relatively low (tranquillizers by 4%; strictly 'psychotropic' drugs by 0.3% to 0.6% of the population). These findings are similar to those reported in English-speaking countries. Data analysis showed that socio-cultural factors (age, sex, marital status and profession) influence the frequency and type of drug intake. The definition of drug abuse and addiction used (increase of dosage, inappropriate use, effect changes) proved somewhat unreliable and called into question the criteria used for diagnosis and categorization of persons at risk. In view of the results of previous studies and the importance attached by critics, an unexpected finding of this survey was the minor influence exerted by tranquillizers on road traffic safety. However, the number of cases for individual drug classes was relatively small and there is a need for more broadly based studies of a similar design before reaching firm conclusions.

A prospective study was carried out in 15 patients with peripheral obstructive arterial disease (Fontaine Stage II), with obstructions in the thigh region, to assess the effect of treatment with pentoxifylline on clinical and haemodynamically measurable factors, particularly changes in the post-ischaemic increase in peripheral blood pressure. After a 7-day wash-out period, patients were hospitalized for 1 week and received a daily infusion of 300 mg pentoxifylline plus a 600 mg tablet orally in the evening. They were then treated as out-patients for 2 weeks, receiving 1200 mg pentoxifylline orally per day. Pain-free and maximum possible walking ranges, using a treadmill ergometer, were determined on Days 7, 14, 21 and 28 of the study. Measurements were made at the same intervals, using Doppler ultrasound, and the peripheral resting blood pressure index and post-ischaemic blood pressure index calculated. The results showed significant improvement in both pain-free and maximum walking range after intravenous and oral therapy and this was particularly noticeable in those patients who, before treatment, had a walking range of less than 150 metres: their pain-free range doubled in the first week. There was a slight increase in the resting Doppler blood pressure indices during treatment and a clear, significant increase in the post-ischaemic pressure index 90 and 120 sec after the induced ischaemia ended.

The protective effect of xanthines against E. coli-induced and cytokine-induced lung injury in guinea-pigs has been demonstrated recently. In the present study, the possible protective effects were examined of an analogue of pentoxifylline, HWA-138, a xanthine derivative, on lung injury in septic guinea-pigs. Three groups of animals were studied over a period of 8 hours: Group I animals--saline control injected intravenously with 3 ml 2% lysine/normal saline followed by a continuous lysine/saline infusion (1 ml/kg/hr); Group II--septic control injected intravenously with 2 x 10(9)/kg Escherichia coli followed by a continuous lysine/saline infusion (1 ml/kg/hr); and Group III--E. coli septicaemia plus HWA-138 continuous infusion (HWA-138 dissolved in lysine/saline) began with a bolus (10 mg/kg) followed by a HWA-138 continuous infusion (3 mg/kg/hr) started 60 minutes before injection of E. coli. Arterial blood pressure and white blood cell counts were monitored serially for 8 hours. Lung water (wet-to-dry ratio) and the concentration ratio of 125I-labelled albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared to plasma (125I-albumin BAL/plasma, 125I-albumin lung/plasma) were examined. Results demonstrated that an intravenous injection of E. coli caused an increased W/D ratio (p less than 0.01) and an increased 125I-albumin lung/plasma ratio (p less than 0.01). In contrast, the HWA-138-treated group did not demonstrate significantly increased W/D lung ratios (p less than 0.01) and 125I-albumin lung/plasma ratios (p less than 0.05). The data suggest a possible role for HWA-138 in attenuating sepsis-induced lung injury.

A double-blind study was carried out in 48 hospitalized, elderly demented patients with key symptoms of aggressiveness and agitation to evaluate the efficacy and tolerability of zuclopenthixol compared with that of haloperidol/levomepromazine. Patients were allocated at random to receive initial doses of either 4 mg zuclopenthixol daily or 1 mg haloperidol in the morning and 5 mg levomepromazine in the evening over a period of 4 weeks. In Week 4, the mean daily dose was 4.8 mg zuclopenthixol and 1.6/7.6 mg haloperidol/levomepromazine, respectively. After 1 week, the severity of illness was already significantly reduced, and was further reduced after 2 and 4 weeks of treatment in both groups: the reduction, however, was most pronounced in the zuclopenthixol group and after 2 weeks this difference was significant. Side-effects were few. The results of the study indicate that, whilst both zuclopenthixol and haloperidol/levomepromazine were effective and well tolerated in these elderly patients with aggressiveness and agitation, onset of therapeutic effect appeared more rapidly with zuclopenthixol, which furthermore provides the practical advantage that it may be administered once a day.

An open clinical trial was carried out in 21 chronic schizophrenics to assess the effectiveness and side-effects of treatment with depot neuroleptics. All patients had been stabilized on fluphenazine decanoate for at least 6 months and on entry to the study were given the choice of continuing with this treatment or changing over to flupenthixol decanoate. Sixteen patients chose to receive flupenthixol decanoate (40 mg) and the other 5 fluphenazine decanoate (25 mg). Doses were given every 4 weeks during the 12-week study period. Clinical assessments were carried out every 4 weeks (Weeks 0, 4, 8 and 12) using the Brief Psychiatric Rating Scale and a side-effects checklist, and the Hamilton Rating Scale for Depression, the Schedule for Affected Disorders and Schizophrenia--Change Version, and the Global Assessment Scale were completed on entry (Week 0) and at the end of the study (Week 12). The results indicated that symptoms of depression, withdrawal, worrying, and psychomotor retardation were improved significantly (p less than 0.05) more with flupenthixol than with fluphenazine. The frequency of side-effects decreased during treatment with flupenthixol and there was a tendency towards fewer side-effects in the flupenthixol group than in the fluphenazine group after 8 weeks of treatment. It is concluded that a group of schizophrenic patients characterized by depressive symptoms or side-effects attributable to a prescribed neuroleptic might benefit from a switch to flupenthixol treatment.

In a double-blind, placebo-controlled crossover trial, the effects of ramipril, a long-acting non-sulphydryl angiotensin I converting enzyme inhibitor, on phenprocoumon steady-state pharmacodynamics were investigated in 8 healthy male volunteers taking individually fixed doses of phenprocoumon. The results showed that 5 mg ramipril or placebo once daily for 7 days did not alter the anticoagulant response (Quick values) to phenprocoumon after a stabilization phase of 2 weeks. Mean Quick values during the steady-state phase with ramipril and placebo were 67.5% and 69.3%, respectively. The clotting factors II, VII, IX and X as well as protein C decreased in the run-in phase and remained stable both during ramipril and placebo treatment. There were no differences between ramipril or placebo treatments. As the phenprocoumon dosage was kept unchanged during the double-blind phase, the results indicate that ramipril does not interfere with the vitamin K-dependent cascade.

A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

A study was carried out in 68 otherwise healthy male naval crew members to assess the long-term effectiveness and side-effects of routine transdermal scopolamine administration for the prevention of seasickness. The transdermal patches were applied to the mastoid process before each sailing and the subjects generally used 2 patches a week. Check-ups were made every 3 months over a period of 3 years. The average reported seasickness severity (on a scale of 0 to 7) after 6 months at sea prior to the administration of transdermal scopolamine was 5.64 +/- 0.11 (mean +/- S.E.M.), in comparison with 3.14 +/- 0.23 post-administration (p less than 0.001). A significant improvement was found in the self-estimated performance at sea whilst receiving the drug: 65.7% +/- 3.38% (mean +/- S.E.M.), compared to 25% +/- 2.24% beforehand (p less than 0.001). Contact dermatitis precluded the use of transdermal scopolamine in 3 (4.4%) subjects. The only other significant side-effect was dryness of mucous membranes. In conclusion, transdermal scopolamine was found to be effective in the prevention of seasickness and improvement of performance at sea during 3 years of follow-up and routine administration of the drug was not complicated either by severe side-effects or by performance disturbances.

A randomized, multi-centre trial was carried out in 152 hospitalized women with pelvic inflammatory disease to evaluate the efficacy and tolerability of amoxycillin/clavulanic acid compared with that of a standard regimen using three antimicrobial agents (aminopenicillin, an aminoglycoside and metronidazole). Seventy patients initially received 3 to 4 intravenous doses per day of 1 g amoxycillin/200 mg clavulanic acid (mean 7.7 days) and then 4 to 6 tablets per day of 500 mg amoxycillin/125 mg clavulanic acid (mean 11.2 days). The other group of 82 patients initially received parenteral therapy daily (mean 7.7 days) with a combination of 3 to 4 g amoxycillin or ampicillin, 160 mg gentamicin (or 150 mg dibekacin or tobramycin) and 1.5 g metronidazole, and then oral therapy with 2 to 3 g amoxycillin or ampicillin and 1 to 1.5 g metronidazole daily (11.1 days). Clinical results, assessed at discharge from hospital (mean 10 days in both groups), were comparable in both groups, with 96% complete or partial response and no failures in the amoxycillin/clavulanic acid group, and 90% complete or partial successes and 5 failures with the triple therapy regimen. Both treatments were well tolerated and very few side-effects were reported.