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)

The aim of this randomized, double-blind trial of postoperative thoracic epidural analgesic infusions was to determine whether clonidine at 10 microg/h (group C10, n = 22), 15 microg/h (Group C15, n = 24), or 20 microg/h (Group C20, n = 24) improved postoperative analgesia in patients undergoing abdominal gynecologic surgery, without side effects or hemodynamic changes, when added to a 5-mL/h infusion of 0.125% bupivacaine and fentanyl 2 microg/mL (Group CO, n = 22). The 24-h study infusion was supplemented, as required, by patient-controlled epidural fentanyl. Groups were similar for age, weight, duration, and type of surgery. Clonidine produced a dose-dependent improvement in analgesia at rest. Only 20 microg/h significantly increased the percentage of patients who experienced no pain with coughing (relative risk 1.44, 95% confidence interval 1.24-1.94), reduced pain scores with coughing (P < 0.05), and significantly lowered supplementary fentanyl requirements (P < 0.05). Groups were similar for sedation, pruritus, nausea, time to ambulation, and satisfaction with analgesia. Clonidine produced a dose-dependent decrease in blood pressure and pulse rate and an increase in vasopressor requirement (P < 0.01). Epidural clonidine infused at 20 microg/h improves analgesia during coughing when combined with epidural bupivacaine-fentanyl in patients undergoing lower abdominal surgery but is associated with hemodynamic changes and increased vasopressor requirement.
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PMID:Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl. 917 14

Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1.4. Three disulfide-deficient analogues of KIIIA were initially synthesized in which the native disulfide bridge formed between either C1-C9, C2-C15, or C4-C16 was removed. Deletion of the first bridge only slightly affected the peptide's bioactivity. To further minimize this analogue, the N-terminal residue was removed and two nonessential serine residues were replaced by a single 5-amino-3-oxapentanoic acid residue. The resulting "polytide" analogue retained the ability to block sodium channels and to produce analgesia. Until now, the peptidomimetic approach applied to conotoxins has progressed only modestly at best; thus, the disulfide-deficient analogues containing backbone spacers provide an alternative advance toward the development of conopeptide-based therapeutics.
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PMID:Structurally minimized mu-conotoxin analogues as sodium channel blockers: implications for designing conopeptide-based therapeutics. 1910 60