British journal of clinical pharmacology
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Br J Clin Pharmacol · Oct 1980
Randomized Controlled Trial Clinical TrialMethodological considerations in the evaluation of analgesic combinations: acetaminophen (paracetamol) and hydrocodone in postpartum pain.
1 In a double-blind study, 108 postpartum patients received single oral doses of either placebo, acetaminophen (paracetamol) 1000 mg, hydrocodone 10 mg, the combination of acetaminophen plus hydrocodone, or codeine 60 mg. 2 In the 2X2 factorial analysis, both the acetaminophen and hydrocodone effects were statistically significant, whereas the interaction contrast was not. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the assumption that these constituents are producing analgesia by different mechanisms. 3 Although significantly superior to placebo, codeine seemed to be inferior to the other treatments. 4 Compared with placebo, both codeine and hydrocodone (centrally acting narcotics) seemed relatively more effective in uterine cramp than episiotomy pain; the reverse seemed true with acetaminophen (a peripherally acting analgesic). 5 Some methodological implications for the evaluation of analgesic combinations are discussed.
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1 The intensity of postoperative pain is influenced by many factors, for example, individual variation, site of incision and type of operation, anaesthetic technique, and the interval from the end of operation to the appearance of pain. 2 These factors affect the efficacy of analgesics. 3 Mild analgesics provide adequate pain relief in half of our patients in the immediate postoperative phase when the pain is slight to moderate. 4 The maximum effect of mild analgesics corresponds to that produced by morphine 6-10 mg. Adequate analgesia may not therefore be provided for the treatment of severe postoperative pain unless narcotic analgesics have been used peroperatively. 5 When mild analgesics are combined with narcotics synergism is achieved. 6 As postoperative pain decreases with time, mild analgesics usually provide adequate pain relief on the first and following postoperative days.
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Br J Clin Pharmacol · Feb 1980
Elevated blood histamine levels and mast cell degranulation in solar urticaria.
1 Ultraviolet radiation (UVR)-induced wealing was studied in four patients with solar urticaria, whose measured action spectra were within the range 300 to 700 nm. 2 Elevated histamine levels were found in blood draining wealed skin in all four patients. 3 Histological and electron microscopial studies of the irradiated skin showed evidence of mast cell degranulation. 4 These findings demonstrate an association between histamine release from mast cells and wealing in solar urticaria, and should encourage evaluation of drugs which suppress histamine release in this disorder.
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Br J Clin Pharmacol · May 1979
Interaction of halothane with non-depolarizing neuromuscular blocking drugs in man.
1 Tetanic and single twitch contractions of the adductor pollicis muscles, in response to indirect stimulation of each ulnar nerve, were recorded in patients anaesthetized with thiopentone and nitrous oxide in oxygen. 2 Concentrations of 1 and 2% halothane were administered for 10 min during recovery from neuromuscular paralysis by tubocurarine, dimethyl tubocurarine and gallamine. 3 During exposure to halothane, the peak contraction of the tetanic response was reduced and tetanic fade was increased whereas the single twitch was unaffected. 4 The effects of halothane on the tetanic responses were readily antagonized by intravenous neostigmine preceded by atropine. 5 Halothane could act post-synaptically by a non-depolarizing block or by desensitizing the post-synaptic receptors, but a pre-synaptic action seems more likely since neuromuscular block was only evident when tetanic stimulation was applied. Such an effect could be caused by impairment of the release of acetylcholine.