Drugs
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The traditional classification of nonsteroidal anti-inflammatory drugs (NSAIDs) as exclusively 'peripherally acting' agents is no longer valid. For many of these agents there is a growing body of evidence in favour of an additional central mechanism for their anti-inflammatory and analgesic effects. This view is further supported by the recent discovery that a substantial component of the hyperalgesia and allodynia that characterise postinjury hypersensitivity occurs in the CNS, notably the spinal dorsal horn. ⋯ Despite much effort, it remains a formidable task to assess the significance of these differential mechanisms upon clinical pain states. In the meantime, however, it may be possible, on the basis of in vivo studies, to evaluate the impact of putative spinal analgesic mechanisms that are unrelated to inhibition of prostaglandin synthesis. This approach has recently been extended to include the identification of pharmacokinetic and clinical correlates of these derived in vivo parameters, and in this way attempt to demonstrate clinical relevance.
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The optimal treatment of pain requires an understanding of the mechanisms involved. Pain is a sensory end-point that can be generated by a number of dissimilar processes. Consequently, the concept of treating pain as a unitary symptom is obsolete. ⋯ Clinical pain is more than a reflection of sustained peripheral input and it is, to a large extent, the expression of changes produced in the CNS, including the phenomenon of central sensitization. We need to treat both the disease/injury process in the periphery and the changes it induces or triggers in the CNS. Prevention of central sensitization will substantially eliminate the hyperalgesia and allodynia that patients find so distressing, and it offers new possibilities for the development of novel analgesics or antihypersensitivity drugs.
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(+/-)-Tramadol is a central analgesic with low affinity for opioid receptors. The rate of production of its M1 metabolite (O-demethyl tramadol) is influenced by debrisoquine-type polymorphism, and this metabolite shows a higher affinity for opioid receptors than the parent drug. Experimental and clinical data suggest that tramadol may also exert its analgesic effect through direct modulation of central monaminergic pathways. ⋯ Approximately 2-fold accumulation of the parent compound and the M1 metabolite may be expected during multiple dose treatment. The duration of analgesic effect after a single oral dose of tramadol 100 mg is about 6 hours. Clinical experience has confirmed that tramadol is an effective and relatively safe analgesic that may be of value in several pain conditions not requiring treatment with strong opioids.
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This paper reviews the use of tramadol in the management of acute pain. Tramadol is a weak opioid analgesic with a potency comparable to that of pethidine. While it is not recommended as a supplement to general anaesthesia because of its insufficient sedative activity, tramadol has been successful in the treatment of postoperative pain. ⋯ There have been only a few studies of oral or spinal application of tramadol in acute pain states. Tramadol has also been used for the control of pain associated with labour and acute myocardial infarction, as well as for the management of trauma pain. In summary, tramadol can be recommended as a basic analgesic for the treatment of patients with moderate to severe pain.