Overuse of acid suppressive therapy in hospitalised patients with pulmonary diseases.

OBJECTIVES: Overuse of acid suppressive therapy (AST) has been reported in hospitalised patients, but the use in specific patient categories is unexplored. We assessed the use of and indication for AST and upper endoscopic investigations in hospitalised patients on a pulmonary ward compared with patients on other wards. METHODS: 301 patients were enrolled in the study. 162 were hospitalised on a pulmonary ward with a control group consisting of 139 from both a surgical and general internal medicine ward. Adequate indications for AST were those strongly supported by medical literature. RESULTS: Among the 301 patients enrolled, 132 (44%) used AST. 78 (59%) had no adequate indication for AST. On the pulmonary ward 79 (49%) patients used AST, compared to only 10 (20%) on the internal medicine ward (P < 0.05). On the pulmonary ward 68% of the patients had no adequate indication for AST, which was more common than inappropriate use of ASTon the control wards (P < 0.05). The most common inadequate indication for AST was peptic ulcer prophylaxis during corticoidsteroid therapy. CONCLUSION: In hospitalised patients a significant overuse of AST was observed, particularly among pulmonary patients. More adequate use of AST can contribute to substantial savings for the health-care system.

The clinical relevance of the interaction between carbamazepine and dextropropoxyphene in elderly patients in Gothenburg, Sweden.

OBJECTIVES: To evaluate the clinical importance of the interaction between carbamazepine (CBZ) and dextropropoxyphene in elderly patients. METHODS: All patients (n = 7263) in Gothenburg, Sweden, who were part of a drug-dispensing programme, were included in the study. Eight per cent of the patients took CBZ and 18% took dextropropoxyphene, continuously. Patients who used a combination of these drugs were compared with patients who took only CBZ or dextropropoxyphene or neither of the two drugs. These four groups of patients were matched to each other with reference to gender, age and concomitant medication, which finally resulted in 21 patients in each group. A questionnaire with 30 symptoms of well-being, including symptoms typical of adverse effects of CBZ, were answered by the patients with the help of a registered nurse. Venous blood samples were drawn from the patients for the analysis of CBZ, its metabolite CBZ 10,11-epoxide (CBZ-E) and dextropropoxyphene. RESULTS: The doses of CBZ and dextropropoxyphene were lower among patients who used the combination of the two drugs than among those who only used one of the drugs. The mean level of CBZ in serum (S-CBZ) was, however, significantly higher and the level of CBZ-E in serum (S-CBZ-E) significantly lower among the patients who used the combination of CBZ and dextropropoxyphene, thus indicating an inhibition of the metabolism of CBZ. The prevalence of symptoms indicating side effects of CBZ was significantly higher in the group of patients who used both drugs. CONCLUSION: This study has shown that the combination of CBZ and dextropropoxyphene is hazardous in elderly patients and should be used with caution.

The influence of Rx-to-OTC changes on drug sales. Experiences from Sweden 1980-1994.

OBJECTIVE: A descriptive study of national sales data from Sweden to find out the effect of over-the-counter (OTC) switches on total sales of a number of drugs. During the period 1980-94, 16 drugs were changed from prescription only (Rx) status to the Swedish OTC market. Total sales increased for 14 out of these 16 drugs. The increase was seen soon after the change to OTC status. Two years after the change an average increase of 36% was seen. In the following 2 years, the increase was typically very modest (average 1%). Large differences in the changes were seen for the individual drugs. The prescription of OTC packs decreased on average by 26% during the first 2 years after the switch. Converting this decrease in sales in terms of number of packs no longer prescribed led to an estimated yearly saving of SEK 200 million ($US 30 million) for the national drug budget. Taking account of the total increase in defined daily doses (DDDs) 2 years after the change for those 16 drugs led to an estimated yearly saving of SEK 2.5 billion ($US 400 million).

Pharmacodynamics of oxypurinol after administration of allopurinol to healthy subjects.

1. Eight healthy subjects received 50, 100, 300, 600 and 900 mg allopurinol daily for 1 week each, in random order with 1 week separating each treatment period. The pre-dose plasma concentration of oxypurinol, the extent of inhibition of xanthine oxidase, plasma urate concentration and urine urate excretion rate were assessed on the last 2 days of each treatment week. 2. The ratio of 1-methyluric acid (1MU) over 1-methylxanthine (1MX) in the urine, following a dose of 50 mg 1MX infused intravenously over 20 min, was used to measure the inhibition of xanthine oxidase. 3. The steady-state plasma concentration of oxypurinol increased linearly with increasing dose of allopurinol between 50 mg to 600 mg day-1, with a weak indication of saturation at the higher 900 mg day-1 dose rate. 4. The relationships between plasma oxypurinol concentration and xanthine oxidase inhibition (1MU/1MX ratio), plasma urate concentration and urine urate excretion rate were fitted to an inhibition sigmoid Emax model and the C50 values for oxypurinol were 26.38 +/- 4.87, (mean +/- s.d.) 36.58 +/- 8.36 and 24.61 +/- 9.08 microM, respectively. 5. 1MU/1MX ratio appeared to be a reliable index of xanthine oxidase activity in vivo as the C50 for oxypurinol observed for 1MU/1MX ratio, plasma urate concentration and urine urate excretion rate were similar. 6. The concentration of oxypurinol required for inhibition of xanthine oxidase, as indicated by C50, was lower than those often observed in clinical practice.

Potential drug--drug interactions in 5,125 mostly elderly out-patients in Gothenburg, Sweden.

Of 5,125 mostly elderly out-patients, average age 78.2 years, 1,594 (31%) had at least one interacting drug combination according to the Swedish National Formulary. On average, each patient with drug-drug interactions (DDIs) had 1.6 DDIs. There was no difference in the sex or age between those having DDIs and those without. However, patients with one or more DDIs used a significantly larger number of drugs than those without DDIs, on average 8.1 versus 5.2. This significant difference was independent of age and sex. When classified for clinical significance according to the handbook "Drug Interactions and Updates" by Hansten and Horn, 155 (3%) patients had interactions of 'major clinical significance'. The most common were interactions between beta-adrenergic blockers and antidiabetics, followed by potassium-sparing diuretics and potassium, and carbamazepine and dextropropoxyphene. The methodology allows us to screen routinely for DDIs and to plan further studies with emphasis on clinical outcome.