Sangeeta Sharma | Central University oh Himachal Pradesh (original) (raw)

Uploads

Papers by Sangeeta Sharma

Drug Development Research, 1995

In this study, the antinociceptivc activity of five non-steroidal anti-inflammatory drugs (NSAIDs... more In this study, the antinociceptivc activity of five non-steroidal anti-inflammatory drugs (NSAIDs) was determined in two animal models of different pain intensity and compared with their capacity t o produce motor incoordination and death. Intravenous clonixine, diclofenac, dipyrone (metamizole), ketorolac, and piroxicam produced dose-dependent antinociception in the acetylcholine-induced writhing test with E D , , values ranging from 14 (clonixine) to 205 (dipyrone) pmol/kg. The behavioral responses in the 55°C hot plate assay were also inhibited in a dosedependent manner, but significantly higher doses were required to display antinociceptive activity, the E D , , values ranging from 116 (clonixine) to 2,263 (dipyrone) pmol/kg. In the writhing test, the antinociceptive effects of NSAlDs were present at doses far below those producing toxic effects. In contrast, their E D , , values against a more intense nociceptive stimulus approached those producing lethal effects so that the therapeutic ratios were very small, ranging from 1.3 (diclofenac) to 3.0 (dipyrone). The antinociceptive activity of the reference drug morphine is striking, since both types of nociceptive responses were eliminated at doses substantially lower than those producing death (therapeutic ratios of 502 and 121). Morphine exhibited the highest antinociceptive efficacy, followed by dipyrone, ketorolac, clonixine, and piroxicam. Diclofenac showed a more limited efficacy. These findings imply potential risks for patients treated iv with this class of drugs and suggest caution in the use of high doses of NSAIDs. Future development of injectable NSAlD formulations should include a detailed analysis of adverse reactions following iv administration of high doses.

Drug Development Research, 1995

In this study, the antinociceptivc activity of five non-steroidal anti-inflammatory drugs (NSAIDs... more In this study, the antinociceptivc activity of five non-steroidal anti-inflammatory drugs (NSAIDs) was determined in two animal models of different pain intensity and compared with their capacity t o produce motor incoordination and death. Intravenous clonixine, diclofenac, dipyrone (metamizole), ketorolac, and piroxicam produced dose-dependent antinociception in the acetylcholine-induced writhing test with E D , , values ranging from 14 (clonixine) to 205 (dipyrone) pmol/kg. The behavioral responses in the 55°C hot plate assay were also inhibited in a dosedependent manner, but significantly higher doses were required to display antinociceptive activity, the E D , , values ranging from 116 (clonixine) to 2,263 (dipyrone) pmol/kg. In the writhing test, the antinociceptive effects of NSAlDs were present at doses far below those producing toxic effects. In contrast, their E D , , values against a more intense nociceptive stimulus approached those producing lethal effects so that the therapeutic ratios were very small, ranging from 1.3 (diclofenac) to 3.0 (dipyrone). The antinociceptive activity of the reference drug morphine is striking, since both types of nociceptive responses were eliminated at doses substantially lower than those producing death (therapeutic ratios of 502 and 121). Morphine exhibited the highest antinociceptive efficacy, followed by dipyrone, ketorolac, clonixine, and piroxicam. Diclofenac showed a more limited efficacy. These findings imply potential risks for patients treated iv with this class of drugs and suggest caution in the use of high doses of NSAIDs. Future development of injectable NSAlD formulations should include a detailed analysis of adverse reactions following iv administration of high doses.