Non-opioid Analgesics

The second group of non-opioid analgesics, which are not classified as NSAIDs, consists of substances that lack anti-inflammatory properties, such as phenazones, metamizole (dipyrone) and paracetamol. Their molecules are neutral or weakly basic, have no hydrophilic... 

Pain management is an important component of therapy and is similar to that of acute pancreatitis. Non-opioid analgesics are preferred, but the severe and persistent nature of the pain often requires opioid therapy. Patients can require chronic doses of opioid analgesics, with a resulting risk of addiction. Pain can also be managed by removing the stimulus of exacerbation if identified.31,38... 

Mild 1-3/10 Non-opioid analgesic regular scheduled dosing Acetaminophen 1000 mg every 6 hours Ibuprofen 600 mg every 6 hours Consider adding an adjunct or using an alternate regimen if pain is not reduced in 1-2 days... 

Daly, J.W. GarrafTo, H.M. Spande, T.F. Decker, M.W. Sullivan, J.P. Williams, M. (2000) Alkaloids from frog skin the discovery of epibatidine and the potoitial for developing novel non-opioid analgesics. Nat. Prod. Rep., 17, 131-5. 

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

White PF The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005 101 S5. 

Analgesics and anesthetics adequately cover pain management and are sometimes used with adjuvant therapies such as sedatives, antidepressants and anxiolytics. In the following sections, and for convenience, general pain therapy will refer to opioid and non-opioid analgesics that normally are given orally (or... 

Almost all non-opioid analgesics are non-steroidal anti-inflammatory drugs (NSAIDs) and have varying degrees of analgesic, anti-inflammatory and antipyretic activity. Acetylsalicylic acid (Aspirin ), used to relieve mild to moderate pain and certain types of severe pain, is the archetypal NSAID and is probably the best known and most used therapeutic drug worldwide. 

Bannon, A. W., Decker, M. W., Holladay, M. W., Curzon, P., Donnelly-Roberts, D. L., Puttfarcken, P. S., Bitner, R. S., Diaz, A., Dickenson, A. H., Porsolt, R. D., Williams, M., Arneric, S. P. Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors, Science 1998, 279, 77-81. 

All agonists in this therapeutic group decrease the sensation of painful stimuli, which is their main clinical application. They tend to subdue dull, persistent pain rather than sharp pain, but this difference is to some extent dose dependent. The major difference between the non-opioid analgesics such as aspirin and the opiates is that the former reduce the perception of peripherally mediated pain, by reducing the synthesis of local hormones that activate the pain fibres, whereas the latter attenuate the affective reaction to pain without affecting the perception of pain. This clearly suggests that the site of action of the opiate analgesics is in the central nervous system. 

Figure 2.13 Minor structural modifications of the antihistaminic drug diphenhydramine 39 (Figure 2.11) produced the anticholinergic drug orphenadrine 45 and the non-opioid analgesic nefopam 46.

Nefopam is a centrally acting non-opioid analgesic used for mild to moderate pain its mechanism of action is uncertain but may be due to an inhibition of serotonin, noradrenaline and dopamine reuptake. It is considered by some to act on GABA B receptors and is likely to interact with other drugs affecting these neuro transmitters,... 

Inoue M, Nakayamada H, Tokuyama S, Ueda H (1997) Peripheral non-opioid analgesic effects of kyotorphin in mice. Neurosd Lett 236 60-62... 

Nefopam, an orphenadrine derivative, is a centrally acting non-opioid analgesic. Various adverse effects have been reported, including nausea, vomiting, epigastric pain, dizziness, drowsiness and mental confusion, hypotension, tachycardia, skin rashes, xerostomia, and urinary retention some of these may be related to its anticholinergic properties (SEDA-11, 100). Its unsatisfactory adverse effects profile was confirmed in two studies of pain control in cancer and rheumatoid arthritis (SEDA-15, 104)... 

W 2964M) is a pyridylcarbamate, a non-opioid analgesic, with an undefined mode of action. It is a possible (NMDA) GLUTAMATE RECEPTOR ANTAGONIST. 

The nicotinic acetylcholine receptor antagonist ( )-epibatidine 285 is a potent, non-opioid analgesic that can be prepared by a cross-coupling reaction [100]. The advanced intermediate 284 was assembled by the Pd-catalyzed reaction of 282 with 283. o... 

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