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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opiate and opioid analgesics are commonly used for pain in general and presumably for headache. Codeine, oxycodone and propoxyphene, among the most commonly prescribed, do carry some risk of abuse, and their efficacy in headache patients has not been well studied. In many patients with other kinds of pain, however, both of neoplastic and non-neoplastic origin, chronic opiate use has been demonstrated to be of benefit without adverse side effects. The type of headache patient with intractable pain who needs frequent opiate analgesic and who does not develop addiction or drug abuse is an important subject for research.
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PMID:Opiate and opioid use in patients with refractory headache. 769 12

Codeine is an analgesic commonly used to relieve pain in the early post partum. Its metabolite, morphine, is probably responsible for its effectiveness in this use. However, morphine may also cause neonatal apnea. We studied free codeine and morphine levels in breastmilk of 17 samples from seven mothers and neonatal plasma of 24 samples from 11 healthy, term neonates. Levels were determined by radioimmunoassay. Milk codeine levels ranged from 33.8 to 314 ng/ml 20 to 240 minutes after codeine; morphine levels ranged from 1.9 to 20.5 ng/ml. Infant plasma samples one to four hours after feeding had codeine levels ranging from < 0.8 to 4.5 ng/ml; morphine ranged from < 0.5 to 2.2 ng/ml. Low infant plasma levels are secondary to low excretion into milk and the small amounts of milk available in the first few days. Moderate codeine use during this time (< or = four 60 mg doses) is probably safe.
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PMID:Codeine and the breastfed neonate. 826 56

The potential benefits of a nonsteroidal antiinflammatory drug to 67 patients undergoing knee arthroscopy were evaluated in a prospective, randomized, placebo-controlled, double-blinded study. Group A received the drug (diclofenac, 75 mg twice daily) for 3 to 5 days before and for 7 days after surgery. Group B received a placebo preoperatively and the drug postoperatively. Group C received a placebo at both times. Codeine was available postoperatively for all patients if needed. Outcomes reported by the subjects included pain, crutch use, and return to activities. Outcomes assessed by physicians included knee effusion, range of motion, and gait. Knee flexion and extension strengths were measured isokinetically pre- and postoperatively. Pain scores on the 1st postoperative day were higher in Group C than in Group A. Pain scores at all other time points were not significantly different in the three treatment groups. Groups A and B required less codeine during the first 72 hours after surgery than Group C (mean, 2.9 +/- 1.0 versus 6.8 +/- 1.0 pills). Recovery of function, recovery of strength, and physical examination parameters were not significantly different in the three treatment groups. Diclofenac was an effective analgesic in the immediate postoperative period. Recovery from arthroscopy, however, was not enhanced by taking the drug.
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PMID:An evaluation of pre- and postoperative nonsteroidal antiinflammatory drugs in patients undergoing knee arthroscopy. A prospective, randomized, double-blinded study. 836 10

A dilute solution of formalin (20 microliters of 10% formalin) was injected subcutaneously in the dorsal right hind paw of the naked mole-rat. The injection of the dilute formalin produced two periods of pain behaviour, the early (0-5 minutes) and the late phase (25-60 minutes). These were quantified as the total time spent licking the injected paw. Codeine phosphate (10, 25 or 50 mg kg-1) significantly reduced pain behaviour in both the early and late phase. Codeine administration also induced aggressive, hyperactive behaviour and motor impairment that was naloxone (2 mg kg-1) reversible. Naproxen (200 mg kg-1) and dexamethasone phosphate (30 mg kg-1) significantly reduced licking activity in the late phase only.
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PMID:Effects of codeine, naproxen and dexamethasone on formalin-induced pain in the naked mole-rat. 845 32

Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain. However, there are few controlled clinical trials of single-entity codeine in chronic cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain. Thirty-five patients with chronic cancer pain were randomized in a double-blind crossover study to controlled-release (CR) codeine or placebo, for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of "rescue" acetaminophen-plus-codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 +/- 9.8 years) with a mean daily CR codeine dose of 277 +/- 77 mg (range, 200-400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 +/- 18 mm versus 36 +/- 20 mm, P = 0.0001), categorical pain intensity scores (1.2 +/- 0.8 versus 1.8 +/- 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day. Daily "rescue" analgesic consumption was significantly lower on CR codeine, compared to placebo treatment (2.2 +/- 2.3 versus 4.6 +/- 2.8 tablets per day, P = 0.0001). Both patients and investigators preferred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR codeine, given every 12 hr results in significant reductions in pain intensity and the use of "rescue" acetaminophen-plus-codeine in patients with cancer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.
J Pain Symptom Manage 1995 Nov
PMID:Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain. 859 22

Codeine is an old drug that is still widely used to treat mild and moderate pain. It is mainly metabolised by glucuronidation, but minor pathways are N-demethylation to norcodeine and O-demethylation to morphine. The latter pathway depends on the genetically polymorphic CYP2D6 which is absent in 7% of the white population (PM) and present in the remainder (EM). Lack of influence of codeine on experimental pain in PM as well as in EM treated with the CYP2D6 blocker quinidine, who are both practically unable to convert codeine to morphine, has supported an old hypothesis that codeine acts through metabolically formed morphine. Possibly, local codeine O-demethylation in the CNS is of major importance for its hypoalgesic effect. Such a local morphine formation from codeine, which supposedly is also catalysed by CYP2D6, could explain why the hypoalgesic effect of codeine stems from morphine despite relatively low plasma levels of morphine after standard hypoalgesic doses of codeine. Dependence of codeine hypoalgesia on morphine formation via CYP2D6 makes this effect liable to interaction with drugs that are inhibitors of CYP2D6. Examples of potent inhibitors of CYP2D6 are quinidine, some selective serotonin reuptake inhibitors and some neuroleptics. Less potent inhibitors, such as tricyclic antidepressants, will probably also reduce the pain relieving effect of codeine, since codeine has a low affinity for CYP2D6. Biosynthesis of morphine in humans may also include steps catalyse by CYP2D6. Experimental studies in large groups of EM and PM indicate that this may lead to interphenotype differences in pain tolerance.
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PMID:The pharmacogenetics of codeine hypoalgesia. 884 55

The purpose of this review was to identify and analyze the controlled clinical trial data for peripheral neuropathic pain (PNP) and complex regional pain syndromes (CRPS). A total of 72 articles were found, which included 92 controlled drug trials using 48 different treatments. The methods of these studies were critically reviewed and the results summarized and compared. The PNP trial literature gave consistent support (two or more trials) for the analgesic effectiveness of tricyclic antidepressants, intravenous and topical lidocaine, intravenous ketamine, carbamazepine and topical aspirin. There was limited support (one trial) for the analgesic effectiveness of oral, topical and epidural clonidine and for subcutaneous ketamine. The trial data were contradictory for mexiletine, phenytoin, topical capsaicin, oral non-steroidal anti-inflammatory medication, and intravenous morphine. Analysis of the trial methods indicated that mexiletine and intravenous morphine were probably effective analgesics for PNP, while non-steroidals were probably ineffective. Codeine, magnesium chloride, propranolol, lorazepam, and intravenous phentolamine all failed to provide analgesia in single trials. There were no long-term data supporting the analgesic effectiveness of any drug and the etiology of the neuropathy did not predict treatment outcome. Review of the controlled trial literature for CRPS identified several potential problems with current clinical practices. The trial data only gave consistent support for analgesia with corticosteroids, which had long-term effectiveness. There was limited support for the analgesic effectiveness of topical dimethylsulfoxyde (DMSO), epidural clonidine and intravenous regional blocks (IVRBs) with bretylium and ketanserin. The trial data were contradictory for intranasal calcitonin and intravenous phentolamine and analysis of the trial methods indicated that both treatments were probably ineffective for most patients. There were consistent trial data indicating that guanethidine and reserpine IVRBs were ineffective, and limited trial data indicating that droperidol and atropine IVRBs were ineffective. No placebo controlled data were available to evaluated sympathetic ganglion blocks (SGBs) with local anesthetics, surgical sympathectomy, or physical therapy. Only the capsaicin trials presented data which allowed for meta-analysis. This meta-analysis demonstrated a significant capsaicin effect with a pooled odds ratio of 2.35 (95% confidence intervals 1.48, 3.22). The methods scores were higher (P < 0.01) for the PNP trials (66.2 +/- 1.5, n = 66) than the CRPS trials (57.6 +/- 2.9, n = 26). The CRPS trials tended to use less subjects and were less likely to use placebo controls, double-blinding, or perform statistical tests for differences in outcome measures between groups. There was almost no overlap in the controlled trial literature between treatments for PNP and CRPS, and treatments used in both conditions (intravenous phentolamine and epidural clonidine) had similar results.
Pain 1997 Nov
PMID:A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. 1006 78

This study was conducted to compare the analgesic action of Lysine Clonixinate (LC) vs Paracetamol/Codeine association (PC) in the treatment of postepisiotomy pain in primiparae women: 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and randomly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours. Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale (VAS) and patient's assessment before receiving treatment and after 1, 2, 6 and 24 hours. Intensity of spontaneous pain was reduced in 24 hours from 4.28 +/- 2.11 to 1.73 +/- 1.46 (P < 0.0001) in the LC group and from 4.78 +/- 2.08 to 1.90 +/- 1.72 in the PC-treated group (p < 0.0001); with no significant differences between treatments. 54% of the patients treated with LC and 55% of those receiving PC showed onset of analgesic action 30 minutes following dose administration. Patient's final global assessment revealed that 95% of LC-treated patients and 96% of the PC group showed total or partial pain relief during the first treatment day. No sleep disturbances were seen during the night in 75% of patients. Only one patient receiving LC showed nausea not requiring treatment discontinuation. It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain.
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PMID:Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. 950 93

Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.
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PMID:Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. 965 May 46

The analgesic effect and adverse events of the weak opioid codeine is assumed to be mediated by its metabolite morphine. The cytochrome P-450 enzyme CYP2D6 catalysing the formation of morphine exhibits a genetic polymorphism. Two distinct phenotypes, the extensive (EMs) and poor metabolisers (PMs), are present in the population. The prevalence of PMs in the Caucasian population is 7% to 10%. Since PMs do not express functional CYP2D6, they have a severely impaired capacity to metabolise drugs which are substrates of this enzyme. Provided the analgesic effect and the adverse events of codeine are mediated by its metabolite morphine, large phenotype-related differences are to be expected and PMs, as they form only trace amounts of morphine, can serve as a model to test the hypothesis whether the analgesia and adverse events of codeine are mediated by the parent drug or its metabolite morphine. Therefore we have studied in a randomised placebo-controlled double-blind trial the analgesic effect of 170 mg codeine (p.o.) compared to 20 mg morphine (p.o.) and placebo in 9 EMs and 9 PMs using the cold pressor test. The duration and intensity of the side effects were assessed using visual analogue scales (VAS). Codeine and morphine concentrations were measured in serum and urine. Compared to placebo, 20 mg morphine caused a significant increase in pain tolerance in both phenotypes, EMs and PMs (16.2+/-27.4 vs. -0.66+/-27.4 s x h, n=18). However, following administration of codeine, analgesia was only observed in EMs but not in PMs (EMs: 54.9+/-42.2 vs. 1.7+/-4.2 s x h, P < 0.01; PMs: 9.6+/-10.9 vs. 3.3+/-23.7 s x h, not significant). Adverse events were significantly more pronounced after morphine and codeine compared to placebo in both EMs and PMs. In contrast to the phenotype-related differences in the analgesic effect of codeine, however, no difference in adverse events between the phenotypes could be observed. In the pharmacokinetic studies, significant differences between the two phenotypes in the formation of morphine after codeine administration could be observed. Whereas morphine plasma concentrations were similar in PMs (Cmax: 44+/-13 nmol/l: AUC: 199+/-45 nmol x h/l) and EMs (Cmax: 48+/-17 nmol/l); AUC: 210+/-65 nmol x h/l) after morphine administration, following 170 mg codeine, morphine plasma concentrations comparable to those after morphine application were only observed in EMs (Cmax: 38+/-16 nmol/l; AUC: 173+/-90 nmol x h/l). In PMs only traces of morphine could be detected in plasma (Cmax: 2+/-1 nmol/l; AUC: 10+/-7 nmol x h/l). The percentage of the codeine dose converted to morphine and its metabolites was 3.9% in EMs and 0.17% in PMs. The interindividual variability in analgesia of codeine which is related to genetically determined differences in the formation of morphine clearly indicate that this metabolite is responsible for the analgesic effect of codeine. In contrast to the analgesic effect, frequency and intensity of the adverse events did not present significant differences between the two phenotypes. These findings have implications for the clinical use of codeine. Since side effects occurred in both EM and PM subjects, the use of codeine as an analgesic will expose 7% to 10% of patients who are PMs to the side effects of the drug without providing any beneficial analgesic effects.
Pain 1998 May
PMID:Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. 969 56


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