[Analgesics: use, poisonings, too much?].
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Biomedical subjects
Publications and source records attributed to J P Kampmann.
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A number of randomised studies indicate that a single high dose of aminoglycoside every 24 h may be more efficient and less toxic than the same dose divided into multiple daily doses. In the meta-analysis of 16 studies described here, which included more than 1200 patients, the relative chance (i.e. the relative risk, RR) of cure of the single-dose regime compared with the multiple-dose regime was 1.027, indicating that the single daily dose regime had a 2.7% higher cure rate (NS). The RR of avoiding nephrotoxicity was 1.001 (NS) and the RR of avoiding ototoxicity was 1.001 (NS). It is concluded that there is no difference concerning efficacy and safety between single-dose and multiple-dose regimes for administration of aminoglycosides.
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Two different beclomethasone dipropionate inhalation aerosols (Andion and Becotide) were compared in a double-blind, cross-over study in patients with stable, steroid-dependent asthma. Fifty-two patients were included in the study, and 44 completed the two 6-week periods of treatment. The difference in therapeutic efficacy on FEV1 between Andion and Becotide was -0.018 1, and likewise no differences in therapeutic efficacy on FVC and peak expiratory flow were found. There were no significant differences between the two treatment periods regarding peak expiratory flow rates, symptoms, frequency of adverse effects, and amount of salbutamol and beclomethasone dipropionate employed. In conclusion, no significant differences could be demonstrated between Andion and Becotide with regard to pulmonary function, symptoms, and frequency of adverse effects in the treatment of patients with steroid-dependent bronchial asthma.
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Patient's knowledge about their own medicine is often insufficient, and this is possibly a contributory factor for noncompliance. We interviewed 65 patients (median age 61 years) from an out-patient clinic with free access and 86 patients (median age 68 years) from a hospital outpatient clinic. In both groups, knowledge about the dosage and the adverse effects of the drugs was poor. Old age and polypharmacy were associated with poor knowledge; there were no differences as regards knowledge between the two out-patient clinics. The 86 patients from the hospitals out-patient clinic were randomised to either 30 minutes of extended verbal information or to the standard information of the department. At the subsequent visit eight weeks later, a repeated interview indicated, that the informed group had generally improved knowledge about their own medication, while this was not the case in the control group. A statistically significant difference between the groups was, however, only found for medication knowledge about side effects. It is concluded that out-patients knowledge about their own medication is often poor, but can be improved by verbal information.
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Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three-compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0-49.1%); the distribution volume at steady state, 2.3 l/kg (range, 1.0-3.5 l/kg); clearance (CL), 7.6 ml/min/kg (range, 4.8-10.8 ml/min/kg); and t1/2(z) 7.9 h (range, 3.2-13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups, whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time, because cyclosporin absorption seems to follow zero-order kinetics.
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To study a potential interaction between digoxin and two non-steroid anti-inflammatory drugs, indomethacin (50 mg three times daily) and ibuprofen (600 mg three times daily) were given for 10 days to 10 and 8 patients, respectively, on chronic digoxin treatment. Serum digoxin measured by fluorescence polarisation immunoassay increased significantly (P less than 0.05) during treatment with indomethacin from pre-treatment values of 0.73 +/- 0.34 nmol l-1 (mean +/- s.d.) to a mean value of 1.02 +/- 0.43 nmol l-1, while administration of ibuprofen did not change the steady state serum concentration of digoxin. The result demonstrates that some non-steroidal anti-inflammatory drugs such as indomethacin increase serum digoxin to levels high in the therapeutic range. This should be taken into consideration when co-administering other drugs known to increase the serum concentration of digoxin such as several antiarrhythmics.
The pharmacokinetics of each of the enantiomers of disopyramide were examined after i.v. bolus administration of 150 mg racemic drug in a randomized cross-over study before and after the administration of cimetidine 400 mg twice daily orally. Clearance and volume of distribution (Vz) of total drug were significantly (P less than 0.001) higher for the R-(-) enantiomer than the S-(+) enantiomer (7.9 vs 4.6 l h-1 and 89 vs 50 l, respectively), whereas no significant difference in half-life could be demonstrated. The clearance of free drug was significantly (P less than 0.05) higher for the S-(+) enantiomer than that of the R-(-) enantiomer (34.6 +/- 5.4 l h-1 vs 27.2 +/- 5.6 l h-1), whereas no significant enantioselective difference in unbound volumes of distribution (258 +/- 38 l vs 226 +/- 42 l) could be demonstrated. Coadministration of cimetidine did not alter the pharmacokinetics of disopyramide. A significant concentration- or time-related decrease in the renal clearance of each of the enantiomers measured with respect to total drug in serum was observed, whereas renal clearances of the free enantiomers were similar.
Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.
The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted due to acute exacerbation of chronic bronchitis seems of no help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.
The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted on account of acute exacerbation of chronic bronchitis does not appear to help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast, general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.
Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double-blind cross-over study comparing two seven-days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO2 increased insignificantly (0.05 less than P less than 0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO2 decreased by 0.12 kPa (P greater than 0.10). There was no correlation between changes in PaCO2 and changes in PaO2. FVC, FEV1 and dyspnoea at rest were unchanged. Gastrointestinal side effects were reported significantly (P less than 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects.
Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.
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