Der Schmerz
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According to the German Drug Law of 1976 the present status of scientific knowledge regarding the benefit/risk-ratio of combination analgesics was reevaluated and is summarized taking the fixed combination of paracetamol plus acetylsalicylic acid as an example. The extensive discussion of the responsible committee for reevaluation of drugs B-3 (Neurology/Psychiatry) at the German Federal Institute of Health (Bundesgesundheitsamt) led to the following results as viewed by the involved members: - the fixed combination has its pharmacological rationale (secure detoxification, even with high single doses; (over)additive analgesic effect in experimental models. - the benefit of the fixed combination is given by a potentially lower liver toxicity as proven with experimental models and by an (over)additive efficacy in cancer pain or headache. - combination-specific risks surpassing the ones of the single substances are not recognizable. ⋯ Even though the clinical efficacy has been proven only in few specific studies the evaluation of the benefit/risk-ratio appears to be positive regarding the not recognizable combination-specific risks. The combination is recommended for acute use.
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alpha(2)-Adrenoceptor agonists like clonidine, dexmedetomidine, and ST-91, inhibit nociceptive reflex activity predominantly by a spinal mode of action. They mimic the action of the inhibitory transmitter noradrenaline, which is released from the terminals of bulbospinal monoaminergic pathways. The inhibition by noradrenaline is due partly to hyperpolarization of the postsynaptic neuronal membrane; however, the selective antinociceptive effect of the alpha(2)-adrenoceptor agonists results from reduction of the release of the excitatory transmitters such as glutamate and substance P, blockade of the binding of substance P to spinal neurones, and enhancement of the action of the inhibitory transmitter, 5-hydroxytryptamine. ⋯ Moreover, impulse conduction in C fibres of peripheral nerves is far more reduced by these compounds than that in A fibres. Antinociceptive effects are reported to occur in various models of clinical pain, e.g. the formalin test, adjuvans-induced arthritis, autotomy following deafferentation, and "hyperalgesia" after nerve ligation. Therefore, the mechanisms involved in antinociception may also be responsible for the analgesia produced by alpha(2)-adrenoceptor agonists.
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Two cases with perineal pain caused by recurrent carcinoma of the rectum are reported. Initially both patients suffered from predominantly nociceptive pain, which was treated adequately with spinal opioids. Tumor growth with epidural spread and infiltration of the plexus lumbosacralis caused severe neuropathic pain. ⋯ Bradycardia and hypotension occurred with initial dose titration and after dose increases and were treated with parasympathicolytic drugs and vasopressor agents. Both patients were given spinal clonidine until their death 4 1/2 and 4 months later. In the final stages, adjuvant systemic administration of morphine was necessary to control dyspnea.