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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.
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PMID:Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats. 3 81

Aspirin and codeine, standard reference analgesics, are frequently used as positive controls in clinical trials of new oral analgesics. In randomized parallel double-blind studies, single doses of aspirin and codeine were compared with placebo in episiotomy pain (99 patients) and in postpartum uterine pain (130 patients), common models in analgesic trials. With aspirin, 600 and 1,200 mg, in episiotomy pain, analgesia as measured by pain intensity difference (PID) scores began within 1 hr, peaked at the second hour (p less than 0.01), and continued to the fifth hour (p less than 0.01). In uterine pain, responses with aspirin, 650 mg, were observed to be equally good. With codeine, 60 mg, in episiotomy pain measurable analgesia was present by the second hour and was significant at the fourth hour (p less than 0.05); in uterine pain, responses were indistinguishable from placebo throughout an 8-hr time-course. Codeine seemed ineffective and therefore umacceptable as a positive control in uterine pain. These data imply that the two postpartum pain models are qualitatively different: episiotomy pain seems sensitive to both aspirin and codeine, while uterine pain appears sensitive to aspirin but not to codeine.
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PMID:Asprin and codeine in two postpartum pain models. 78 93

The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment.
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PMID:Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. 224 79

The present study examined the effect of codeine, a centrally acting opiate, on the respiratory sensations elicited in normal subjects by breathing to exhaustion against externally applied inspiratory threshold loads. Subjects were tested on two separate days following the double-blind, randomized administration of either placebo or codeine (90 mg). The intensity of the sensations of effort and discomfort experienced during two loaded breathing trials (a "high" load that was 73% of the maximum inspiratory pressure (MIP) and a "low" load that was 63% of the MIP) was evaluated using category (Borg) scores on each day of study. To verify that the dosage of codeine administered was sufficient to produce analgesia, we also determined the effect of this dosage on the time that subjects could tolerate immersion of one hand in ice water. Codeine altered neither the perceived effort nor the sense of discomfort associated with breathing against external loads and had no appreciable effect on the time to exhaustion during loaded breathing trials. This dose of codeine did, however, increase the time that ice water immersion could be tolerated and reduced the rate at which the sense of discomfort increased over time during ice water trials. These results indicate that, provided the pressure-time index of respiratory muscle contraction remains constant, analgesic doses of codeine alter neither the sensations elicited by loaded breathing nor the total time that breathing against a fatiguing inspiratory load can be tolerated.
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PMID:Effect of codeine on the sensations elicited by loaded breathing. 235 94

The antinociceptive activity of flupirtine was measured in various test procedures predictive of analgesic activity. In the electrostimulated pain test in mice the oral ED50 for flupirtine was 25.7 mg/kg p.o. Thus, flupirtine was approximately 31.7 times more potent than paracetamol (ED50: 814 mg/kg p.o.) and as potent as pentazocine (ED50: 38.5 mg/kg p.o.). Morphine (ED50: 16.8 mg/kg p.o.) was 1.5 times and buprenorphine (ED50: 2.6 mg/kg p.o.) 9.9 times more potent than flupirtine. In the hot plate test (mice) flupirtine (ED50: 32 mg/kg p.o.) was approximately half as potent as morphine (ED50: 15.5 mg/kg p.o.). The oral and intravenous antinociceptive activity (ED50) of flupirtine in the electrical tooth pulp stimulation test in conscious dogs was 3.5 mg/kg p.o. and 0.7 mg/kg i.v. which was similar to that of pentazocine (ED50: 4.2 mg/kg p.o. and 0.5 mg/kg i.v.). Buprenorphine had, as expected, stronger antinociceptive activity (ED50: 1.0 mg/kg p.o. and 0.04 mg/kg i.v.). Fifteen minutes after oral administration of 40 mg/kg flupirtine, the pain threshold in the electrostimulated pain test was increased by 54%. The maximal antinociceptive effect was observed 30 minutes after dosing. The analgesia lasted at least 75 minutes. Codeine significantly elevated the pain threshold 15 minutes after dosing. Its maximal effect was also reached 30 min after application but the antinociceptive activity wore off earlier than after flupirtine. The intracerebroventricular and intrathecal administration of flupirtine also caused dose dependent antinociceptive activity in dose ranges which, when applied systematically, did not produce analgesia in rats. The antinociceptive activity of flupirtine was not abolished by naloxone whether given orally or by the intraventricular or intrathecal routes. In opiate receptor binding studies flupirtine had no affinity for mu, delta or kappa opiate receptors at the highest concentration used (10(-5) M). Whereas buprenorphine and tramadol showed a striking similarity in the pharmaco-electroencephalogram recorded from different parts of the brain (frontal cortex, thalamus, striatum and the mesencephalic reticular formation) of the freely moving rat, flupirtine was clearly different in action. It produced dose dependent increases in nearly all frequency bands but its effects were different from those of the minor tranquillizer diazepam and the anticonvulsant phenobarbitone. These findings show that the central antinociceptive activity of flupirtine is not based on an opiate mechanism and is not comparable with that of diazepam and phenobarbitone.
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PMID:The antinociceptive activity of flupirtine: a structurally new analgesic. 283 34

The influence of replacing the phenolic hydroxyl by the methoxy group on opioid receptor binding, analgesic and antitussive action was investigated in the corresponding couples morphine-codeine, hydromorphone-hydrocodone and O-desmethyltramadol (L 235)-tramadol. Binding was studied on rat whole brain membranes (without cerebellum) with the radioligands dihydromorphine (mu-site), ethylketocyclazocine (k-site), D-Ala2-D-Leu5-enkephalin (delta-site) and naloxone (no selective binding). Analgesia (tail flick) and antitussive action (NH3-vapour induced cough) was investigated in rats and ED50 values 10 min after i.v. application were calculated to compare efficacy. All free hydroxyl compounds had higher opioid receptor affinities than the corresponding methoxy derivatives and were more active at the mu-site. The methoxy derivatives codeine and tramadol only had low affinities lacking selectivity towards mu-, kappa-, or delta-binding. Hydrocodone in contrast showed strong and mu-selective binding. The hydroxy compounds had higher analgesic activity than the methoxy congeners and analgesia appeared to correlate with mu-binding affinity. Codeine and hydrocodone were weaker antitussives than the corresponding hydroxy compounds, whereas no significant difference was found between O-desmethyltramadol and tramadol. Only in the tramadol group the methoxy substitution increased antitussive potency in relation to analgesic potency.
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PMID:Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. 284 50

In a randomized, double-blind crossover study, 40 patients with postherpetic neuralgia were given single oral doses of clonidine, 0.2 mg, codeine, 120 mg, ibuprofen, 800 mg, or inert placebo. Pain relief and side effects were recorded for 6 hours. Patients reported significantly more relief after clonidine than after the other three treatments. Codeine and ibuprofen were ineffective. Sedation, dizziness, and other side effects were more frequent after clonidine (74%) or codeine (69%) than after placebo (36%) or ibuprofen (28%). Reported pain relief was greater during trials in which side effects were present. A single, mild side effect was associated with as much additional pain relief as multiple, severe side effects. Clonidine's superiority to codeine, which had a similar incidence of side effects, argues for a specific analgesic effect. In addition, side effects may have contributed to clonidine analgesia, perhaps by suggesting to patients that they had received a potent drug.
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PMID:Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo. 328 74

The analgesic effects of meperidine, anileridine, codeine and codeine + acetominophen on surgical and non-surgical pain in 101 patients were assessed using the McGill Pain Questionnaire. The quality of analgesia was determined by analyzing the changes in the pain descriptors chosen 1 hour after medication. Meperidine and anileridine differentially reduced pain qualities rated as "bright-phasic" by a student sample. Codeine and codeine + acetominophen produced similar patterns of analgesia that were homogeneous across "bright-phasic" and "dull-tonic" types of pain. The data suggest the possibility that opioids may differ in the quality of analgesia produced either as dose increases or different opioid receptor types are recruited.
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PMID:Qualitative differences in effects of opioids in man: preliminary evidence for multiple mechanisms of analgesic action. 375 41

Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.
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PMID:An appraisal of codeine as an analgesic: single-dose analysis. 637 Oct 63

The analgesic response to codeine of patients with postpartum uterine-cramp pain has recently met with controversy. To readdress this question, we conducted a new study comparing codeine sulfate, 60 mg (N = 32) and 120 mg (N = 31), with aspirin, 650 mg (N = 34), and placebo (N = 32) in hospitalized women with moderate or severe postpartum uterine cramps treated with single oral doses in a parallel, stratified, randomized, double-blind trial. Subjective reports were used as indices of response, and patients rated pain intensity, pain relief, and side effects at periodic, uniformly conducted interviews for 6 hr. Most measures of analgesia exhibited important differences among the treatments. In patients with undifferentiated pain (N = 129) and in a subset of patients with pure uterine cramps (N = 56; i.e., no concomitant episiotomy), aspirin showed the greatest response, whereas codeine responses were equivocal with no evidence of a positive dose response. In contrast, in a subset of patients with mixed episiotomy-uterine pain (N = 73), 120 mg codeine showed good separation from placebo and compared favorably with aspirin. Codeine, 60 mg, showed a similar trend, and there was a strong suggestion of dose-dependent analgesia. Side effects were not remarkable except for dizziness and drowsiness after 120 mg codeine in all sets and subsets of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Codeine and aspirin analgesia in postpartum uterine cramps: qualitative aspects of quantitative assessments. 661 71


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