1. The influence of four diuretics on renal prostaglandins was investigated in a study designed in two parts (A and B): A, 24 normal subjects on a constant sodium intake received frusemide (80 mg daily), or hydrochlorothiazide (100 mg), or triamterene (200 mg) or spironolactone (300 mg); B, the same subjects were pretreated for 3 days with indomethacin (150 mg daily), which was continued during the 3 day administration of the respective diuretics and during a 2 day post-diuretic period. 2. In study A, only triamterene provoked a rise in urinary prostaglandins E2 and F2 alpha (+ 474 +/- SEM 92%, P less than 0.01, and + 192 +/- 7%, P less than 0.01). In study B, prostaglandins were significantly inhibited in all subjects. After indomethacin, the natriuretic effect of frusemide and spironolactone was reduced by 80 +/- 12% (P less than 0.01) and 54 +/- 11% (P less than 0.001), whereas the natriuresis induced by hydrochlorothiazide and triamterene was unchanged. No correlation was found between urinary PGE2 and F2 alpha and natriuresis. 3. When triamterene was associated with indomethacin, two subjects developed reversible acute renal failure. 4. Plasma renin activity and urinary aldosterone were stimulated by the four diuretics in study A, but their response was blunted in study B. Urinary antidiuretic hormone was not modified by diuretics but was suppressed by indomethacin. 5. Diflunisal, a structurally unrelated nonsteroidal anti-inflammatory drug, given to 12 of the subjects provoked similar interactions with frusemide, hydrochlorothiazide and spironolactone. 6. The results suggest that prostaglandins contribute to the natriuretic effects of frusemide and spironolactone, but not to those of hydrochlorothiazide and triamterene.
Oxprenolol is a non-selective~-adrenoceptor blocking drug extensively metabolized in the liver. Forty milligrams of oxprenolol were given p.o. to 6 hemodialyzed patients and 7 healthy subjects. Blood concentration profiles of oxprenolol and of the glucuronide Of oxprenolol, the main blood derivative, were determined. Simultaneously the effect of the drug on exercise tachycardia was recorded.In patients with renal failure, both the area under the curve of blood concentration versus time and the peak blood concentrations were higher than in healthy subjects. Blood concentrations of oxprenolol decreased rapidly (mean half-life for patient 1.02 ± SD 0.40 h and for healthy subjects 1.26 ± 0.46 h). During the interdializis interval, there is, in practice, no elimination of glucuronide derivatives. Despite very high blood concentrations of oxprenolol glucuronide, no back transformation into active oxprenolol could be measured.A 40 mg dose of oxprenolol produced higher blood concentrations of oxprenolol in the patients than in the healthy subjects. Inspite of this, this dose did not result in any major difference in cardiac effect between patients and healthy subjects. Thus, administration of oxprenolol does not require dosage adjustement in patients with severe renal failure.
Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) represents the most frequent and difficult problem related to this new form of treatment of ESRD patients. Various treatments have been reported previously. The aim of this study was to investigate the efficiency of a standardized initial treatment in 45 episodes of peritonitis. This was designed to be rapidly efficient, devoided of side-effects and easy enough to be performed by the patients themselves. When peritonitis was clinically suspected, patients received intraperitoneal co-trimoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole), in each of the four daily bags concomitantly with 1,000 U heparin during 2 weeks and half of this dose during 2 other weeks. Our results demonstrate that 88% of the isolates were sensitive to co-trimoxazole and 85% of the patients completed this treatment. All were cured and no relapses were observed. Only 18 days of hospitalisation were required in the 45 episodes of peritonitis. Another anti-infective agent was used in 3 cases of gram-negative peritonitis and 4 other initially resistant to co-trimoxazole. It is concluded that initial treatment of CAPD peritonitis with co-trimoxazole is justified by the high proportion of sensitive germs and that it represents a safe, efficient and inexpensive treatment.
1. Chronic ambulatory peritoneal dialysis allows good control of blood pressure in patients with hypertensive end-stage renal disease. The role of the renin-angiotensin-aldosterone system has therefore been studied in seven patients during the first 6 months of chronic ambulatory peritoneal dialysis treatment.2. Steady increases in plasma renin activity and aldosterone were observed with a good correlation between these two variables. Plasma electrolytes, renin substrate and body weight did not change significantly.3. Angiotensin I1 perfusion tests, performed at the end of the study, showed a relative vascular resistance to angiotensin 11. 4. Stimulation of the renin-angiotensinaldosterone system may be partially explained by this last observation or by removal of an unknown vasopressor substance responsible for the inhibition of the plasma renin activity.
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