Prostaglandin synthetase inhibitors

Paradoxically, the thia2ides are efficacious, especially if combined with a prostaglandin synthetase inhibitor such as indomethacin or aspirin, in the treatment of nephrogenic diabetes insidipus, in which the patient s renal tubules fail to reabsorb water despite the excessive production of ADH (28). Thia2ides can decrease the urine volume up to 50% in these patients. 

Pugh WJ, Sambo K. (1988). Prostaglandin synthetase inhibitors in feverfew. J Pharm Pharmacol. 40(10) 743-45. 

As a prostaglandin synthetase inhibitor, diflunisal exhibits analgesic, fever-reducing, and anti-inflammatory action. It is used for long- and short-lasting symptomatic relief of low to moderate pain in osteoarthritis and rheumatoid arthritis.Synonyms for this drug are dolobid, adomal, noladol, and others. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

Two pyrrole derivatives bearing a significant structural resemblence to indomethacin are tolmetin (10) and chlopirac (11) (78MI30600, 76MI30600). Tolmetin has received clinical comparison with aspirin and with indomethacin in rheumatoid arthritis and generally was found to have comparable effectiveness, but a somewhat diminished tendency to cause lesions in the digestive tract. Like indomethacin, it seems to function as a prostaglandin synthetase inhibitor. 

Moncada S, Ferreira SH, Vane JR. Sensitization of pain receptors of dog knee joint by prostaglandins. In Robinson HJ, Vane JR, editors. Prostaglandin Synthetase Inhibitors. New York Raven Press, 1974 189. 

C. L. Joyce and L. J. D. Zaneveld. Vaginal contraceptive activity of hyuluronidsse and cyckroaiygenase (prostaglandin synthetase) inhibitors in (he rabbit. Fert. Ster. 44 426 (1985). 

Zwergel U, Zwergel T, Ziegler M (1991) Effects of prostaglandins and prostaglandin synthetase inhibitors on acutely obstructed kidneys in the dog. Urol Int 47 64-69... 

Levin DL, Fixler DE, Morriss FC, Tyson J. Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors. J Pediatr 1978 92(3) 478-83. 

Hendricks SK, Smith JR, Moore DE, Brown ZA. Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour. Br J Obstet Gynaecol 1990 97(4) 312-16. 

H.J. Robinson and J.R. Vane, Ed., Prostaglandin Synthetase Inhibitors," Raven Press, New York, 1974. 

In addition to eliciting a contact hypersensitivity response, benzo[a]pyrene has been shown to suppress this response, to other sensitizers. The effects of dermally applied benzo[a]pyrene (alone or following dermal pretreatment with the prostaglandin synthetase inhibitor, indomethacin) on contact hypersensitivity (cell-mediated immunity), and production of antibodies to dinitrophenol (DNP) (humoral immunity) were studied in male BALB/c mice treated for 6 weeks to 6 months (Andrews et al. 1991a). A group of mice treated with acetone served as controls. Benzo[a]pyrene alone caused a significant reduction (p<0.01) in the contact hypersensitivity response to dinitrofluorobenzene (DNFB) as measured by increases in ear thickness when compared to the vehicle controls. However, indomethacin pretreatment prevented the benzo[a]pyrene-induced contact hypersensitivity response. Benzo[a]pyrene also reduced antibody titres to DNP in treated mice. This suppressive effect on humoral immune function was not restored by pretreatment with indomethacin. These findings led the authors to conclude that the mechanism of... 

Effect of prostaglandin synthetase inhibitors on non-analgesic actions of morphine... 

Influence of prostaglandin synthetase inhibitors on the analgesic activity of morphine in the rat... 

Cole, C.H. and O Regan, S. (1981). Effects of treatment with prostaglandin synthetase inhibitors in the erythrocyte sodium transport abnormality in Bartter s syndrome. Pediatr. Res., 15, 926-29... 

Carter, C. A., MithoUand, R.J., Shea, W., and Ip, MM. (1983) Effect of the Prostaglandin Synthetase Inhibitor Indomethacin on 7,12-Dimethylbenz(fl)Anthracene-Induced Mammary Tumorigenesis in Rats Fed Different Levels of Fat, Cancer Res. 43,3559-3562. 

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