Protection from gastrointestinal side-effects by azapropazone by its incorporation into a glucose-sodium acid citrate formulation.

Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non-steroidal anti-inflammatory drugs.

Changes in blood pressure, serum potassium and electrolytes with a combination of triamterene and a low dose of chlorthalidone.

A controlled study was carried out in patients with mild to moderate hypertension to compare the efficacy and tolerability of chlorthalidone alone and chlorthalidone combined with the potassium-sparing diuretic triamterene. After a 4-week period on placebo, 129 patients were allocated at random to receive 1 tablet daily of either 25 mg chlorthalidone (67 patients) or 25 mg chlorthalidone plus 50 mg triamterene (62 patients) for 10 weeks. Ninety-one patients (48 who had received chlorthalidone alone and 43 the combination) entered the third part of the study. During this 6-week period there was a partial crossover, approximately half continuing with their existing medication and the other half with the alternative treatment. All patients were then treated for a final 2 weeks with placebo. The placebo periods were single-blind, the active treatment periods were double-blind. Patients were seen at regular intervals throughout the trial. At each visit, measurements were taken of blood pressure and pulse rate and routine haematological and biochemical tests made. The results showed that both treatments produced similar, clinically significant reductions in blood pressure within the first 4 weeks of active medication and by the end of the 10-week period 51% of those on chlorthalidone alone and 57% on the combination showed a decrease of at least 10 mmHg or to less than 90 mmHg in standing diastolic pressure. Serum potassium decreased with both therapies but was less with the combination than with chlorthalidone alone, and the incidence of a serum potassium less than 3.5 mmol/l was significantly less with the combination. After crossover, blood pressure control was maintained but serum potassium decreased in patients changed from the combination to chlorthalidone alone and increased in those changed from chlorthalidone alone to the combination. Few adverse effects were reported and were generally mild and similar in frequency with the two therapies.

A comparison of three ways of measuring pain.

In a double-blind cross-over trial of azapropazone and indomethacin in 20 patients with osteoarthritis of the hip and knee with four weeks on each drug, three methods of assessing pain and pain relief were used. These methods were a simple five-point rating scale, an analogue scale and an eight-point scale using pictures. Acceptable correlation was shown between all three scales in measurement of changes in degree of pain. The picture scale could be useful in patients with language or mental capacity difficulties.

Adverse reactions to alclofenac.

By far the largest proportion of adverse reactions reported with the use of alclofenac relate to skin rashes. Estimates of the incidence of rash in approximately 1,500 patients participating in clinical trials suggest that this reaction occurred principally with the tablet (10.3%) rather than the later capsule formulation (2.1%) and since the tablet form has been discontinued there have been fewer reports. Detailed investigation of medical records and re-examination of patients developing a rash with alclofenac therapy indicate that there may be a "cross-sensitivity" between alclofenac and other drugs such as penicillin, gold salts and salicylates. Other adverse reactions to alclofenac, such as gastro-intestinal haemorrhage and blood disorders, have been reported only rarely.