Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Remifentanil (Ultiva), a fentanyl derivative, is an ultra-short acting, nonspecific esterase-metabolised, selective mu-opioid receptor agonist, with a pharmacodynamic profile typical of opioid analgesic agents. Notably, the esterase linkage in remifentanil results in a unique and favourable pharmacokinetic profile for this class of agent. Adjunctive intravenous remifentanil during general anaesthesia is an effective and generally well tolerated opioid analgesic in a broad spectrum of patients, including adults and paediatric patients, undergoing several types of surgical procedures in both the inpatient and outpatient setting. Remifentanil is efficacious in combination with intravenous or volatile hypnotic agents, with these regimens generally being at least as effective as fentanyl- or alfentanil-containing regimens in terms of attenuation of haemodynamic, autonomic and somatic intraoperative responses, and postoperative recovery parameters. The rapid offset of action and short context-sensitive half-time of remifentanil, irrespective of the duration of the infusion, makes the drug a valuable opioid analgesic option for use during balanced general inhalational or total intravenous anaesthesia where rapid, titratable, intense analgesia of variable duration, and a fast and predictable recovery are required.
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PMID:Spotlight on remifentanil for general anaesthesia. 1633 49

In the spinal dorsal horn, activation of the nicotinic acetylcholine receptors (nAChR) by exogenously applied agonists is known to enhance inhibitory synaptic transmission, and to produce analgesia. However, it is still unknown whether endogenously released acetylcholine exerts a tonic inhibition on nociceptive transmission through the nAChRs in the spinal dorsal horn. Here, we report the presence of such a tonic inhibitory mechanism in the spinal dorsal horn in mice. In behavioral experiments, intrathecal (i.t.) injection of non-selective nAChR antagonist mecamylamine and alpha4beta2 subtype-selective antagonist dihydro-beta-erythroidine (DHbetaE) dose-dependently induced thermal and mechanical hyperalgesia in mice while the alpha7-selective antagonist methyllycaconitine (MLA) had no effect. Similarly, antisense knock-down of alpha4 subunit of nAChR, but not alpha7 subunit, in spinal cord induced thermal and mechanical hyperalgesia. In whole-cell patch-clamp experiments in spinal cord slice preparation from adult mice, the frequency of miniature inhibitory postsynaptic currents (mIPSCs) observed in substantia gelatinosa (SG) neurons was decreased by mecamylamine and DHbetaE, but not by MLA. The amplitudes of the mIPSCs were not affected. The nicotinic antagonists decreased the frequency of both GABAergic and glycinergic IPSCs. On the other hand, the nicotinic antagonists had no effect on the excitatory postsynaptic currents (EPSCs). Finally, acetylcholine-esterase inhibitor neostigmine-induced facilitation of IPSC frequencies in SG neurons was inhibited by mecamylamine and DHbetaE. Altogether these findings suggest that nicotinic cholinergic system in the spinal dorsal horn can tonically inhibit nociceptive transmission through presynaptic facilitation of inhibitory neurotransmission in SG via the alpha4beta2 subtype of nAChR.
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PMID:Tonic inhibitory role of alpha4beta2 subtype of nicotinic acetylcholine receptors on nociceptive transmission in the spinal cord in mice. 1678 Oct 69

Recently, with the introduction of the novel mu-opioid receptor agonist remifentanil, anaesthesiologists have acquired a unique tool to provide adequate, titratable and predictable analgesia throughout surgery, without the risk of opioid-related delay in postoperative recovery. This new compound will therefore mandate a change in anaesthesia practice from opioid-restricted to opioid-dominated anaesthesia. It is the first in the class of esterase-metabolized opioids within the 4-anilidopiperidine series of drugs, and it possesses an analgesic potency similar to that of fentanyl. The advantages of remifentanil are mainly related to its unique pharmacokinetics, whereas its pharmacodynamics are the same as those of fentanyl. Because of these characteristics, remifentanil-based anaesthesia allows profound opioid analgesia intraoperatively, with rapid and predictable awakening thereafter. Review of the recent literature reveals the potential of remifentanil for improving analgesia in gynaecological procedures and its theoretical advantage in obstetric procedures.
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PMID:Remifentanil for gynaecological and obstetric procedures. 1701 13

Adjuvants are compounds which by themselves have undesirable side-effects or low potency but in combination with opioids allow a reduction of narcotic dosing for postoperative pain control. Adjuvants are needed for postoperative pain management due to side-effects of opioid analgesics, which hinder recovery, especially in the increasingly utilized ambulatory surgical procedures. NMDA antagonists have psychomimetic side-effects at high doses, but at moderate doses do not cause stereotypic behavior but allow reduction in opioid dose to obtain better pain control. Alpha-2 adrenergic agonists cause sedation, hypotension and bradycardia at moderate doses, but at low doses can be opioid sparing especially in spinal administration. Gabapentin-like compounds have low potency against acute pain, but in combination with opioids allow a reduction in opioid dose with improved analgesia. Corticosteroids may have only a limited role as adjuvants while acetylcholine esterase inhibitors may have too many side-effects. Newer adjuvants will be needed to reduce opioid dose and concomitant side-effects, even more as same day surgeries become more routine.
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PMID:Useful adjuvants for postoperative pain management. 1748 18

Long-acting analgesia is critical for patients suffering from long-acting pain. The purpose of this study was to develop lipid emulsions as parenteral drug delivery systems for morphine and its ester prodrugs. Morphine prodrugs with various alkyl chain lengths, including morphine propionate (MPR), morphine enanthate (MEN), and morphine decanoate (MDE), were synthesized. The prodrugs were stable against chemical hydrolysis in an aqueous solution, but were quickly hydrolyzed to the parent drug when exposed to esterase and plasma. Lipid emulsions were prepared using phosphatidylethanolamine (PE) as an emulsifier, while squalene was used as an inner oil phase. Drug release was found to be a function of the drug/prodrug lipophilicity, with a lower release rate for more-lipophilic drug/prodrugs. The inclusion of morphine and its prodrugs into lipid emulsions retarded their release. Lipid emulsions, which incorporated cholesterol, generally exhibited a drug/prodrug release comparable to that of emulsions without co-emulsifiers. Pluronic F68 (PF68) further slowed down the release of morphine and its prodrugs from the emulsions. The antinociceptive activity through the parenteral administration of these emulsions was examined using a cold ethanol tail-flick study. Compared with an aqueous solution, a prolonged analgesic duration was detected after application of the drug/prodrug emulsions. Incorporation of co-emulsifiers such as PF68 and cholesterol further increased the duration of action. The combination of prodrug strategy and lipid emulsions may be practically useful for improving analgesic therapy with morphine.
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PMID:The delivery and antinociceptive effects of morphine and its ester prodrugs from lipid emulsions. 1815 22


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