thromboxane-a2 and Drug-Hypersensitivity

The major benefits of the perioperative administration of nonsteroidal anti-inflammatory drugs (NSAIDs) are related to the ability of these agents to provide analgesia without cardiovascular or respiratory depression. However, there are several possible adverse effects of NSAIDs. All NSAIDs reduce the synthesis of prostaglandins by the kidneys, but their administration in the perioperative period appears to have little potential for renal toxicity when adequate hydration is maintained and renal function is not dependent on renal prostaglandins. However, NSAIDs may cause impairment of renal function in patients with conditions such as hypovolaemia, congestive cardiac failure, or hepatic cirrhosis, since renal function in these patients may be dependent on the vascular effects of prostaglandins. Platelet aggregation is inhibited by the administration of NSAIDs, and most studies of their haematological effects report that NSAIDs are associated with an increase in bleeding times. In patients with normal haemostatic function before NSAID administration, almost all indices of coagulation remain within the normal range after NSAID treatment. Most studies of perioperative blood loss have reported no significant difference between the effects of NSAIDs and placebo in this regard. The incidence of major allergic reactions in the general population appears to be small with NSAIDs. Overall, NSAIDs appear to be safe and well tolerated drugs with a valuable role to play in the treatment of postoperative pain.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Hemorrhage; Humans; Kidney; Pain, Postoperative; Platelet Aggregation; Postoperative Complications; Prostaglandins; Thromboxane A2

To study pathological significance of circulating thromboxane A2 and prostacyclin in mechanisms of impairment of intrarenal hemodynamics and renal function due to contrast media (CM) in risk group patients and to study protective effects of calcium antagonists in CM nephrotoxicity.. To study plasmic concentrations of TxA2 and prostacyclin, we used radioimmunoassay to measure plasmic TxB2 and 6-keto-prostaglandin F1a in patients with chronic glomerulonephritis (group 1), systemic atherosclerosis and coronary heart disease (group 2). The control group consisted of 23 healthy subjects. Diatrizoate (verografin), a high-osmolar CM, was used (40-60 and 250-400 cc in groups 1 and 2, respectively).. Plasma TxB2 and serum creatinine concentrations were significantly elevated in group 1 after CM infusion compared to the preinfusion period and healthy controls. Plasma 6-keto-prostaglandin F1a in group 1 before CM infusion was lower than in controls after CM infusion. The data in group 2 were similar to those for group 1. Administration of nifedipine before and after introduction of CM prevented a rise in serum creatinine and had beneficial effects on TxA2 and prostacyclin synthesis.. Ionic CM have a renal vasoconstrictive effects mediated by imbalance between vasoconstrictor TxA2 and vasodilator prostacyclin and may be nephrotoxic in risk group patients. The protective effects of calcium antagonists promote normalization of calcium dependent TxA22 and prostacyclin synthesis.

Topics: Adolescent; Adult; Biomarkers; Calcium Channel Blockers; Chronic Disease; Contrast Media; Coronary Disease; Disease Progression; Drug Hypersensitivity; Epoprostenol; Female; Glomerulonephritis; Humans; Kidney; Male; Middle Aged; Renal Circulation; Thromboxane A2

In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness.

Topics: Administration, Inhalation; Air Pollutants; Airway Resistance; Animals; Asthma; Bronchial Hyperreactivity; Drug Hypersensitivity; Female; Guinea Pigs; Histamine; Lung; Methacrylates; Nitrogen Dioxide; Thromboxane A2; Thromboxane-A Synthase; Time Factors