Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Codeine, either used alone or in combination with paracetamol, is the standard step-2 opiate analgesic for children from the age of one year. (2) An oral solution of tramadol, another step-2 opiate analgesic, was recently approved in France for the treatment of children at least three years of age. (3) The only clinical trials of tramadol in this age group focused on short-term treatment of postoperative pain. Tramadol has not been compared with codeine, ibuprofen, or correctly dosed paracetamol (step-1 analgesic). Tramadol has been compared with diclofenac, a nonsteroidal antiinflammatory drug, in a trial that included patients over 11 years of age (including adults), but the results of this trial are uninformative because patients were not blinded and no separate paediatric subgroup analysis was carried out. (4) The adverse effects of tramadol in children appear to be mild but frequent (especially vomiting). (5) As with codeine, deaths have been reported following accidental overdose with oral tramadol in children. (6) There is no justification for prescribing such a potentially harmful drug with poorly documented efficacy.
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PMID:Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children. 1597 57

Controversy persists in relation to the analgesic efficacy of opioids in neuropathic pain. In the present study the effects of acute, subcutaneous administration of the mu-opioid receptor agonists morphine, methadone and codeine were examined in rat models of peripheral and central neuropathic pain. In the spared nerve injury (SNI) and chronic constriction injury (CCI) models of peripheral neuropathic pain, both morphine (6mg/kg) and methadone (3mg/kg) attenuated mechanical allodynia, mechanical hyperalgesia and cold allodynia for up to 1.5h post-injection (P<0.05); codeine (30mg/kg) minimally alleviated mechanical hypersensitivity in SNI, but not CCI rats. When administered to rats with photochemically-induced spinal cord injury (SCI), morphine (2 and 6mg/kg) and methadone (0.5-3mg/kg) robustly attenuated mechanical and cold allodynia for at least 2h post-injection (P<0.05). Codeine (10 and 30mg/kg) also attenuated mechanical and cold allodynia in this model for at least 3h after injection. The magnitude of opioid-mediated antinociception was similar between SNI, SCI and non-injured rats as measured in the tail flick test. At antinociceptive doses, no motor impairment as determined by the rotarod test was observed. The therapeutic window (based on antiallodynia versus ataxia) obtained for codeine, was vastly superior to that obtained with morphine or methadone in SNI and SCI rats. Furthermore, the therapeutic window for codeine in SCI rats was 4-fold greater than in SNI rats. Our results further support the efficacy of mu-opioid receptor agonists in alleviating signs of neuropathic pain in animal models of peripheral and especially central nerve injury.
Pain 2005 Aug
PMID:Comparative actions of the opioid analgesics morphine, methadone and codeine in rat models of peripheral and central neuropathic pain. 1598 17

Opioids have been used for analgesia in nearly all civilizations. In paediatrics their use has become widely accepted for combating severe pain, especially postoperative pain and tumour pain. Receptors in the central nervous system are the best known sites of action of opioids, but the existence of peripheral receptors is also probable. The action depends on whether the opioid is more agonist or antagonist and on the peculiarities of physiology in childhood: in the small child a hyperdynamic blood circulation makes resorption faster, and in newborn and premature infants distribution and excretion are influenced by the different composition of the body and the immaturity of liver and kidney. The best known opioid is morphine, and it is the reference substance with which all other opioids are compared. Fentanyl has been used even for the smallest ventilated prematures in recent times, as it is easy to manage and has an early onset of action. Its depressant action on the respiratory centre is an advantage when attempts of spontaneous breathing make mechanical ventilation difficult. Obstinate constipation is the disadvantage of both morphine and fentanyl, and an exacerbation of hyperbilirubinaemia has been seen with fentanyl. Nalbuphine causes a lower degree of respiratory depression. The newer opioids alfentanil and sufentanil have already been used for the relief of paediatric postoperative pain and during mechanical ventilation, but no special advantages of their use are reported. Meperidine has been favoured especially for postoperative pain, although it appears to have no advantages over morphine. Its active metabolite normeperidine may accumulate and cause seizures; meperidine should not be used in prematures or in children with renal dysfunction. There are few publications on the use of piritramide in paediatric pain. Tramadol is widely used for emergencies, as it has the least sedative action; but it has disadvantages in causing nausea and vomiting. Codeine is widely used for its antitussive action. While the necessity of good analgesia for even the smallest infant cannot be overstated, the opioid used must be carefully selected with reference to the age of the child and the pain to be controlled.
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PMID:[Analgesia with opioids in the paediatric patient.]. 1841 33

Combinations of NSAIDs and opioids are currently employed for the treatment of moderate-to-severe pain in order to obtain an increased analgesic esponse, allowing the use of low doses of each agent, hence limiting side effects. There is active interest in developing combinations for oral adminstration. Therefore, we examined the antinociceptive activity of oral indomethacin and codeine, alone and incombination, in the formalin test in the rat. Both codeine and indomethacin, when given alone, produced a dose-dependent antinociceptive effect. ED30 values were 5.0 +/- 0.31 and 54.8 +/- 5.8 mg/kg for codeine and indomethacin respectively. Codeine-indomethacin combinations also produced a dose-dependent antinociceptive effect. The interaction between these two agents was characterized by isobolographic analysis using a fixed-ratio dosing strategy. Accordingly, the theoretical ED30 of the combination for a pure additive interaction, (i.e., that the combined effect is the result of the sum of the effects of the individual components), was 29.9 +/- 2.9 mg/kg. The observed ED30 for the codeine-indomethacin combination was 21.7 +/- 2.34 mg/kg. Comparison by the Student "t" test showed that there is no statistically significant difference (p > 0.05) between the observed and the theoretical DE30 values and thus a synergistic interaction is ruled out. We conclude that the indomethacin-codeine interaction is additive and does not result in analgesic synergism, unlike other combinations such as codeine-diclofenac. Our results show that, since not all the opioid-NSAID associations result in synergism, the individual components of a combination should be carefully selected, and that mechanisms of synergy may suggest actions of the NSAID partner not previously known.
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PMID:Additive, but not synergistic antinociceptive effect of codeine and indomethacin combinations in the formalin test in the rat. 1860 37

We proposed the use of opioid drug bound covalently to hyaluronan (HA) via ester linkages as a method to prolong drug delivery and to possibly increase the quality of perioperative pain management. The in vitro release profile of morphine conjugated to HA (1.3 million MW) was studied. The influence of parameters such as conjugation site and steric protection of the labile ester bonds was investigated in phosphate buffered saline (PBS) medium. HA--codeine and HA--naloxone conjugates were used as structural controls. Codeine and morphine conjugated via the allylic hydroxyl group had a release half-life of 14.0 days in PBS. Naloxone conjugated via the phenolic hydroxyl group showed a half-life of 0.3 days, and all drugs admixed in HA showed half-lives of 0.1 days. Methyl, ethyl, or n-propyl introduced in vicinal position to the ester bond prolonged release of naloxone with half-lives of 0.5, 4.0, and 4.0 days in PBS, respectively. Incorporation of a methyl group prolonged codeine release with a half-life of 55.0 days in PBS. Drugs were released chemically unaltered from the conjugates as confirmed by LC-MS/MS. Further, morphine was conjugated to divinylsulfone cross-linked HA (Hylan B) particles and the release profiles in rat plasma were studied in vitro and in vivo. Release in rat plasma was faster than in PBS with a half-life of 2.5 days, but the release was similar (ca. 12 days) when a cocktail of protease inhibitors was added to the plasma. Sustained release of morphine was observed in a rat surgical model over 30 h. Morphine was released chemically unaltered from the conjugate and morphine intermediates were not detected in significant amounts as confirmed by LC-MS/MS. These results suggest that the morphine release profile from the HA conjugates depends on the alkyl groups vicinal to the ester and the nature of the leaving group. In rat plasma, hydrolysis seems to be controlled by esterase activity.
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PMID:Hyaluronan-tethered opioid depots: synthetic strategies and release kinetics in vitro and in vivo. 1871 37

Codeine is a common drug widely used in some countries as a pain reliever. The effect of codeine on yeast sucrase activity was studied in this report. Non-competitive inhibition was observed using double reciprocal plot. The K(m) of enzyme did not change in the presence of different concentrations of codeine (0.5- 1.5 mM) and was determined about 11.5 mM. The V(max) of enzyme was determined about 8.8 mM/min, and the V(max) decreased in the presence of codeine. The K(i) of codeine was measured by using the reaction rate and the initial concentration of the inhibitor according to the Dixon plot. The K(i) was found to be 0.42 mM and the IC(50) of codeine was determined about 0.875 mM.
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PMID:Inhibitory effect of codeine on sucrase activity. 1935 18

Codeine is designated as one of the essential medicines of palliative care for symptoms such as pain and diarrhea. Essential drugs for palliative care are drugs that are effective for the treatment of common symptoms in palliative medicine, easily available, and are affordable. Codeine is recommended for the management of mild to moderate pain and is available as a combination product or as a stand-alone opioid. It is a prodrug and exhibits an affinity to micro-opioid receptors 200 times lower than morphine. Codeine is metabolized in the liver to inactive metabolites, which account for 90 percent of the transformed product, and morphine, which accounts for 10 percent of the transformed product and provides the main analgesic effect. The production of morphine is dependent on cytochrome oxidase 2D6 enzyme activity, which may not be fully active in some populations. The purpose of this review is to examine the efficacy of codeine for common symptoms encountered in palliative medicine, which has led to its designation as an essential medicine for palliative care.
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PMID:Role of codeine in palliative care. 2216 39

Codeine is an old and commonly used analgesic agent for mild to moderate pain. It is the prototypical "prodrug" in that its analgesic effect is almost wholly dependent on its biotransformation to morphine, a process that is mediated by the polymorphic cytochrome P450 2D6 enzyme. As such, interindividual variability in codeine metabolism and response is a clinical reality, and there has been much progress in characterizing the genetic causes of this variability in diverse populations. Yet despite the potential for both life-threatening adverse reactions and lack of therapeutic effect, codeine is not commonly indicated for therapeutic drug monitoring. This review will discuss the relative role of pharmacogenetics and therapeutic drug monitoring in predicting and/or maintaining adequate and safe analgesia with codeine. The review will end on a discussion of how the marriage of these 2 fields may provide new insights into the mechanisms of codeine-induced toxicity and analgesia.
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PMID:Is there a role for therapeutic drug monitoring with codeine? 2256 51

Mastocytosis is a rare condition related to an abnormal proliferation of mast cells and their accumulation in tissues. Cutaneous mastocytosis is the most common form and mainly affects newborns and infants. The symptoms are caused by the release of mediators contained in mast cells, including histamine. Mastocytosis may be associated with a mutation in the gene encoding the c-kit receptor. Clinically, there are different dermatological findings, which combine acute cutaneous, digestive, or even hemodynamic manifestations in varying degrees. The diagnosis is confirmed by the histological study of a skin sample. We report here the case of a 4-month-old infant suffering from diffuse cutaneous bullous mastocytosis, a very rare variety of mastocytosis. This infant had an erosive and bullous manifestation of dermatosis, initially confused with impetigo. The proliferation of bullous lesions led to her hospitalization. Codeine intake for pain was responsible for a large and extensive bullous reaction associated with anaphylactic shock. This context of bullous spread occurring after taking codeine led to the suspicion of bullous diffuse cutaneous mastocytosis, a diagnosis that was confirmed histologically. This observation demonstrates the difficulty of mastocytosis diagnosis, mostly due to its rarity, especially in its diffuse bullous forms. The rapid deterioration of this patient, after the codeine prescription, emphasizes the importance of the eviction of histamine-releaser compounds in the management of this disease.
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PMID:[Bullous mastocytosis in infancy: a rare presentation]. 2266 34

Alleviation of pain is a major objective in medicine to increase the quality of life. Analgesics are agents that relieve pain by elevating the pain threshold without disturbing consciousness or altering other sensory modalities. Opium is an isoquinoline alkaloid obtained from poppy plant Papaver somniferum (Papaveraceae). Codeine is an alkaloid prepared from opium or morphine by methylation. Codeine is used as a central analgesic, sedative, hypontic, antinonciceptive, antiperistaltic, and is also recommended in tuberculosis and insomnia due to incessant coughing. The literature information relate mostly to the determination of codeine active components using Gas chromatography (GC), Capillary electrophoresis, Thin layer chromatography, High-performance thin layer chromatography, UV-Vis Spectrophotometry, High-performance liquid chromatography and GC in combination with Mass spectroscopy. This contribution provides a comprehensive review of its analytical and pharmacologic profile of codeine.
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PMID:Recent updates on codeine. 2378 22


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