Agents and actions
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Of the currently available mu agonist drugs, the following are relatively contraindicated: 1. Methadone--unpredictable duration of action [5]. 2. Pethidine--unwanted central effects, metabolised to an active metabolite and too short acting. 3. ⋯ Morphine remains the drug of choice for chronic pain when administered in a sustained release preparation. MS Contin, a slow release oral formulation of morphine, is available and has a predictable duration of action lasting from 8-12 h, while improved formulations are about to be released in the near future in some countries. Prescribers need to take into account the relatively poor oral bioavailability of morphine when calculating the daily morphine dose.
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Clinical Trial
Possible link between anaphylactoid reactions to anaesthetics and chemicals in cosmetics and biocides.
Binding-inhibition studies involving human IgE antibody to suxamethonium, SUX (from a patient with a near-fatal reaction), were performed with five different quaternary ammonium compounds (QAC): three common ingredients of cosmetics and two commonly used disinfectants, cetrimide and benzalkonium. All the five QAC showed immunological cross-reaction with SUX. In addition, at high concentrations, they released histamine from basophils of normal subjects. Thus, QAC may be both sensitizers and histamine releasers.
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Randomized Controlled Trial Clinical Trial
Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis.
Most of the previous studies dealing with the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the synthesis of inflammatory mediators involved in joint damage have been done in cells cultured in vitro or in blood cells from patients treated for short periods of time. In this work we have evaluated the long-term effect of aceclofenac, a new NSAID, and diclofenac on the production of a series of inflammatory mediators by blood cells from 30 patients with severe knee osteoarthritis. Both aceclofenac and diclofenac significantly inhibited prostaglandin E2 (PGE2) synthesis by blood mononuclear and polymorphonuclear cells after 180 days of treatment. ⋯ Interleukin-6 (IL-6) synthesis was not affected by aceclofenac while it was diminished by diclofenac. The decrease in IL-6 in all treated patients was significantly correlated with a worsening of the clinical condition. On the whole, these data could afford a pathogenetic basis for the long-term employment of these drugs in patients with inflammatory conditions.
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E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid], a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor-alpha (TNF-alpha) generation from monocytes/macrophages in vitro. E3330 (1-100 microM) reduced lipopolysaccharide (LPS, 10 mg/ml or 1 microgram/ml)-induced TNF-alpha generation from rat resident and Propionibacterium acnes (P. acnes)-elicited peritoneal macrophages, rat and human monocytes, rat Kupffer cells, and splenic mononuclear cells in a concentration-dependent manner. ⋯ Northern blot analysis showed that LPS-induced expression of TNF-alpha messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF-alpha generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF-alpha mRNA expression.
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Chemically and pharmacologically unrelated molecules release histamine in humans to produce both cutaneous and systemic responses. It has been suggested that molecular changes in the new benzylisoquinoline-derived muscle relaxant, atracurium, make it less likely to cause histamine release. We therefore injected volunteers intradermally with equimolar concentrations of various muscle relaxants, morphine, papaverine (a benzylisoquinoline), and histamine, to evaluate the relative ability of these drugs to cause wheal and flare responses, and mast-cell degranulation. ⋯ Skin biopsies after morphine and atracurium injections revealed mast-cell degranulation. All evaluated benzylisoquinoline muscle relaxants are equipotent histamine releasers at equimolar concentrations. A hydrogenated, benzylisoquinoline-nitrogen-containing ring, present in atracurium but not in papaverine, appears to be the molecular conformation responsible for mast-cell degranulation by atracurium.