AbstractProstaglandins increase urine production, electrolytes excretion, detrusor contraction, micturition pressure, lower urethral pressure and inhibit antidiuretic hormone. We hypothesized that high production of prostaglandins or their dominant action on the urinary system may play a role in the pathogenesis of primary enuresis and nocturnal frequency of micturition. To test this, inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin suppositories or diclofenac sodium, or by carbamazepine, were used in their management. Measurement of urine volume and urinary and serum electrolytes and osmolality were performed before and after treatment with indomethacin. Similar to prostaglandins, nitric oxide (NO) causes natriuresis and diuresis, decreases antidiuretic hormone and relaxes trigone and urethra. We hypothesized that NO may play a role in the primary enuresis. Urinary nitrite, the end product of NO, was measured in enuretics before and after treatment with indomethacin and compared with normal control.
Prostaglandins are increased in urinary obstruction and implicated in the urinary calculus formation. The other aspect of the thesis is to determine whether inhibition of prostaglandin synthesis by short acting NS AID (eg: indomethacin suppository), long acting NSAIDs (eg: tenoxicam i.m or i.v, or piroxicam i.m), selective cyclooxygenase inhibitor (eg: sublingual meloxicam), and by calcium antagonist (eg: sublingual nifedipine), could relieve acute or resistant renal colic and facilitate urinary calculus expulsion. The other aims of the thesis are to demonstrate the efficacy and safety of different methods of drug delivery as i.v, i.m, sublingual, oral or rectal routs and their effects on renal function tests and their importance in emergency situations.
Results showed that indomethacin, diclofenac sodium or carbamazepine significantly reduced frequency of bedwetting in most of the patients with enuresis. Urinary nitrite excretion is elevated in enuretics and was decreased significantly when bedwetting episodes decreased by indomethacin. Indomethacin suppository decreased urine volume, urine electrolytes, clearance of free water, filtered sodium, fractional sodium excretion and reduced significantly bedwetting in patients with small as well as normal functioning bladder capacity. Regarding renal colic, indomethacin, tenoxicam, piroxicam, nifedipine and meloxicam alleviated pain of acute renal colic. Long acting NSAIDs had lower incidence of pain relapse and fewer drug administrations when compared to short acting NSAIDs and spasmolytic/analgesic. Indomethacin or nifedipine facilitated passage of urinary calculus and prevented or reduced pain recurrence.
It could be concluded for the first time that prostaglandin and NO might play a role in the pathogenesis of primary enuresis and frequency of micturition, and inhibition of their production might represent a new line for the management. The mechanism of action of indomethacin might be attributed to the significant reduction of urine volume and sodium excretion in addition to its possible effects on bladder and urethral contraction through inhibition of prostaglandin and NO. Short and long acting NSAIDs, COX-2 inhibitor and calcium antagonist, are safe and effective to alleviate pain of acute renal colic and could facilitate passage of urinary calculus. The different methods of drug administration, including rectal or sublingual which could be selfadministered, are effective and safe in the treatment of the diseases. No significant deterioration in renal functions was encountered after treatment with the drugs. The mode of actions of the drugs in respect to prostaglandin inhibition, NO and calcium influx are discussed.
|Date of Award||Jun 2001|
|Supervisor||Phillip Collier (Supervisor) & T. E. J. Buultjens (Supervisor)|