thromboxane-b2 and atipamezole

The analgesic effects of the non-steroidal anti-inflammatory drugs (NSAIDs) flunixin and dipyrone were assessed in healthy sheep with no pre-existing inflammation, and in sheep with a chronic inflammatory lesion, using a mechanical noxious stimulus. Saline and dexamethasone were given as controls. Blood taken from healthy sheep after NSAID administration was assayed for thromboxane B2 (TxB2) to compare the ability of these drugs to inhibit cyclo-oxygenase. Both flunixin and dipyrone produced a small but statistically significant rise in pain thresholds (18% and 21% of maximum possible effect respectively) in the healthy sheep which peaked at 30 min and had returned to pre-drug values by 2-3 h. In the lame sheep a similar effect occurred but the response was smaller, much more variable and tended to be prolonged. Saline and dexamethasone had no effect on thresholds over 6 h in either group of sheep. The rise in thresholds was prevented by pre-treatment with naloxone (an opioid antagonist) or atipamezole (an alpha 2-adrenergic antagonist) in the healthy sheep. Naloxone and atipamezole had no effect on thresholds when given alone to healthy sheep. Both NSAIDs inhibited the production of TxB2 to a similar extent. These results indicate that central mechanisms may be involved in NSAID analgesia.

Topics: Adrenergic alpha-Antagonists; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Clonixin; Dipyrone; Double-Blind Method; Drug Interactions; Female; Foot Rot; Imidazoles; Injections, Intravenous; Lameness, Animal; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Random Allocation; Sheep; Sheep Diseases; Thromboxane B2

alpha 2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of alpha 2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the alpha 2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an alpha 2-adrenoceptor antagonist.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Dose-Response Relationship, Drug; Drug Interactions; Female; Half-Life; Imidazoles; Injections, Intravenous; Platelet Activation; Respiration; Sheep; Thromboxane B2; Xylazine