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The relative bioavailability of paracetamol after rectal administration of suppositories containing a mixture of paracetamol, codeine phosphate and buclizine hydrochloride in healthy volunteers.

'New' and 'old' suppositories (6 months and 30 months since manufacture) containing 800 mg paracetamol, 16 mg codeine phosphate and 12.5 mg buclizine hydrochloride in an identical base were administered to 10 normal volunteers at an interval of 2 weeks. Blood samples were taken at intervals up to 300 minutes after administration for estimation of paracetamol plasma concentrations using high pressure liquid chromatography. Mean peak concentrations were obtained of 4.75 +/- 0.74 mg/ml at 1.75 hours with the new suppositories and of 4.6 +/- 0.67 mg/ml at 2.0 hours with the old suppositories. The difference was not significant. Mean elimination half-life was 4.4 +/- 0.42 hours and 3.73 +/- 0.28 hours, respectively. Again, the difference was not significant, indicating that the absorption characteristics for the suppositories did not appear to deteriorate with ageing for 24 months. Bioavailability data for paracetamol derived from the results were similar to those reported by other workers who studied suppositories containing paracetamol as the only active ingredient. This indicates that the inclusion of codeine phosphate and buclizine hydrochloride in the suppository formulation investigated in the present study did not affect adversely the absorption of paracetamol.

Acetaminophen↗

Effects of codeine on the agitating force and gastrointestinal transit time in dogs, for use in drug absorption studies.

Drug absorption studies using dogs have been difficult because of different gastrointestinal(GI) conditions between dogs and humans, including dogs' shorter intestinal transit time and strong agitation force in the GI tract. We attempted to modify the agitation force and GI transit time in dogs using codeine. The agitation force was examined based on the in vitro/in vivo correlation for a CR tablet of acetaminophen showing agitation-dependent release. Codeine improved the GI condition better than atropine or loperamide, employed previously.

Acetaminophen↗

Codeine-induced pulmonary edema.

We recently treated a patient with pulmonary edema and an oral overdose of codeine. Although overdoses of other opiate drugs are known to cause pulmonary edema, the association of an overdose of codeine with pulmonary edema has not been reported previously.

Adult↗

Pain management in dental practice: tramadol vs. codeine combinations.

BACKGROUND: Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. First marketed in 1994, tramadol is frequently prescribed by physicians for the management of moderate-to-moderately severe chronic pain. The author evaluates its unique analgesic pharmacology and limited clinical utility for managing acute pain in dentistry. TYPES OF STUDIES REVIEWED: Clinical drug trials in medicine and dentistry were reviewed to assess analgesic efficacy. Postmarketing surveillance studies and reports of adverse drug events were evaluated to determine short- and long-term safety. RESULTS: Tramadol's maximum analgesic efficacy for relieving acute pain after oral surgery appears to be similar to that of 60 milligrams of codeine alone but less than that of a full therapeutic dose of a nonsteroidal anti-inflammatory drug or a codeine combination, such as aspirin/codeine or acetaminophen/codeine. Adverse events reported by patients receiving tramadol therapy since it was approved by the Food and Drug Administration suggest a risk of seizures, drug abuse and anaphylactoid reactions. CLINICAL IMPLICATIONS: Tramadol has limited indication for management of acute pain in dentistry, possibly as an alternative analgesic when gastrointestinal side effects contraindicate the use of nonsteroidal anti-inflammatory drugs and when codeine/acetaminophen combination analgesics are not well-tolerated or are contraindicated.

Acetaminophen↗

Analysis of reaction products of morphine and codeine with hydrogen peroxide by high-performance liquid chromatography/mass spectrometry.

Changes in the chemical structures of morphine and codeine in the presence of hydrogen peroxide, a major component of hair dye and decolorant treatments, were examined with high-performance liquid chromatography/mass spectrometry (LC/MS). A mixture of morphine and hydrogen peroxide solution, after incubation at 39 degrees C for 24 h, produced two reaction products (hydroxymorphines). When codeine was used in place of morphine, one reaction product (hydroxycodeine) was produced, in which the benzene ring was hydroxylated.

Chromatography, High Pressure Liquid↗

GLC/TLC analysis of codeine and morphine in urine via derivatization techniques.

A procedure has been developed for the TLC and GLC analysis of codeine and morphine derivatives in urine in cases where there is too much interference for TLC analysis as free drugs. Urine is hydrolyzed, then split into two fractions. One fraction is extracted with a polar solvent, concentrated, and acetylated. An aliquot is injected in a 3% OV-17 column and the rest is spotted on a plate developed in hexane:chloroform:diethylamine (50:30:6). The other fraction is ethylated (converting morphine to ethylmorphine), extracted with a nonpolar solvent, concentrated, acetylated, concentrated, and then spotted on a plate developed in hexane:n-butanol:acetonitrile:diethylamine (80:5:5:10). Codeine and morphine can be detected without interference at concentrations as low as 0.3 micrograms/mL.

Chromatography, Gas↗

Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain.

The purpose of this double-blind, randomized, parallel, multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery. Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups. There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy. The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group.

Acetaminophen↗

Codeine for child pain: new preparation. Helpful in some cases.

(1) This codeine-based syrup is indicated for the treatment of pain in children. It is the first step 2 analgesic (WHO classification) to become available in France for oral treatment of children. (2) Efficacy and the optimal dose regimen are based mainly on lengthy experience with codeine in other countries. Only a few small trials on acute pain are available. (3) The safety profile is that of all opiates: adverse effects comprise mainly constipation, nausea and vomiting. (4) Accidental ingestion by a young child can lead to severe poisoning.

Acetaminophen↗

[Efficacy and safety of acetaminophen-codeine in the treatment of pain].

The treatment of acute or chronic pain of variable intensity and origin, is efficiently achieved by the association of paracetamol and codeine. At a dose of 1000 mg paracetamol and 60 mg of codeine, this association is considered one of the most efficient as compared to other analgesics of level II in the OMS classification, like tramadol.

Acetaminophen↗

A comparison of the effects of codeine and tramadol on laryngeal reactivity.

The effect of tramadol on laryngeal reflex activity was assessed in a double-blind cross-over study in six volunteers receiving single oral doses of either codeine 50 mg, tramadol 50 mg or tramadol 100 mg. Laryngeal reactivity was measured by the response to the inhalation of dilute ammonia vapour. The minimum ammonia concentration required to induce a glottic stop was recorded prior to drug administration, and at 15, 30, 45, 60, 90, 120, 150 and 180 min thereafter. Psychometric tests were performed at 0, 45 and 105 min to detect any relationship between central sedation and changes in laryngeal reflex activity. The concentration of ammonia required to induce a glottic stop increased in all treatment groups, but more so in the tramadol groups. The time course suggested that the codeine effect peaked early, and had returned to normal within 2 h. For tramadol 100 mg, laryngeal depression appeared to be still increasing at the end of the 3-h study period. No correlation was found between laryngeal and sedative effects. Tramadol is produced as a racemic mixture, in which one isomer acts through an opioid receptor pathway whilst the other affects noradrenergic and serotonergic mechanisms. Both of these routes of action may be involved in the suppression of the response to experimentally induced cough.

Adult↗

Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain.

Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.

Acetaminophen↗

[Codeine: efflorescent crystals].

Investigations in pharmaceutical stocks of drugs have shown a non conformity with registred theorical stocks. This leads us to study the volatilisation of codeine stored in safety boxes suggest adding the mention "slightly efflorescent" to the usual characteristics of codeine found in the monography of the French Pharmacopoea as mentionned by LEBEAU and JANOT.

Codeine↗

Cutaneous responses to histamine, compound 48/80, and codeine in patients with chronic renal failure.

Pruritus is a common symptom associated with chronic renal failure (CRF). But increased plasma histamine levels and skin mast cell proliferation previously reported in these patients did not correlate with the intensity of the pruritus. Since increased mast cell releasability was described in chronic idiopathic urticaria, we attempted to examine whether this mechanism could explain pruritus in patients with CRF. Twenty-five patients with end stage renal failure were skin tested with histamine, codeine, and compound 48/80. There were nine patients on continuous ambulatory peritoneal dialysis, eight patients on hemodialysis, (tested both before and after dialysis) and eight patients with advanced CRF. Wheal area after intradermal injection of three concentrations of the above substances was measured. In general, the wheal areas in all patients with CRF were either similar to or smaller than those of the control group who were without renal impairment. In conclusion, patients with CRF with or without dialysis therapy demonstrated unchanged or decreased skin test responses to histamine, codeine, and compound 48/80. Increased mast cell releasability cannot explain the pruritus in patients with CRF.

Adult↗

Changes of endogenous morphine and codeine contents in the fasting rat.

The alteration of endogenous opiate alkaloids during fasting state was investigated in rats. The concentrations of morphine and codeine in the cortex, midbrain, pons plus medulla, cerebellum, adrenal gland and pancreas were measured using radioimmunoassay for the opiates following high pressure liquid chromatography. The morphine and codeine contents of fasting rats showed maximum elevated levels in cortex, pons plus medulla and pancreas after 2 days of fasting, but after 1 day in midbrain. The opiate content of the cerebellum showed a tendency for a continuous increase during the 4 days. Adrenal glands of fasting rats had elevated levels at days 3 and 4, although there were great fluctuations within the groups.

Adrenal Glands↗

Anaphylaxis following administration of papaveretum. Case report: Implication of IgE antibodies that react with morphine and codeine, and identification of an allergenic determinant.

IgE antibodies that reacted with morphine and codeine were detected in the serum of a subject who experienced a life-threatening anaphylactic reaction following the administration of Omnopon-Scopolamine (papaveretum-hyoscine). Hapten inhibition studies with morphine and a number of structurally-related analogues revealed that morphine and codeine were the most potent inhibitors of IgE binding to a morphine-solid phase. Nalorphine, meperidine, and methadone were also good inhibitors of IgE binding, but naltrexone, buprenorphine, and fentanyl proved to be poor inhibitors. From a detailed examination of structure-activity relationships, the authors conclude that the important structural features of the morphine allergenic (that is, IgE binding) determinant comprises the cyclohexenyl ring with a hydroxyl group at C-6 and, most important of all, a methyl substituent attached to the N atom. The authors' findings suggest that morphine analogues administered to such a patient may provoke clinical anaphylaxis. Hyoscine reacted weakly with IgE antibodies in the subject's serum, but this was thought to be due to weak cross-reaction between this compound and morphine.

Anaphylaxis↗

[Combined propyphenazone and codeine poisoning in childhood (analysis of 6 patients with Spasmoplus poisoning)].

The case histories are presented of 6 patients with accidental poisoning by Spasmoplus suppositories. The main toxic constituents are codeine and the pyrazolone derivative, propyphenazone. All patients had symptoms of codeine intoxication with somnolence, miosis and oedema, 2 patients had also symptoms of prophyphenazone intoxication with hypotension, coma and convulsions. 1 patient died during the acute stage in a state of shock, with arrhythmia, and asystole.

Aminopyrine↗

Comparison of diflunisal and acetaminophen with codeine in the treatment of initial or recurrent acute low back strain.

Effective pain relief and patient tolerance and acceptance are essential in outpatient management of mild to moderate pain of acute low back strain. This study evaluated the efficacy, tolerability, and acceptability of diflunisal and acetaminophen with codeine in patients with mild to moderate pain after an initial or recurrent acute low back strain. Both drugs demonstrated equipotent analgesic efficacy; however, diflunisal was superior to acetaminophen with codeine for patient tolerability and acceptability. The results demonstrated that the study drugs were effective in treating mild to moderate pain caused by acute low back strain in an ambulatory care setting.

Acetaminophen↗

Double-blind comparison of an acetaminophen-codeine-caffeine combination in oral surgery pain.

The purpose of this paper was to evaluate the contribution of low dosages of codeine and caffeine when added to acetaminophen. Subjects were dental outpatients undergoing oral surgery involving bone removal. This was a single-dose, parallel group, double-blind assay evaluting 99 subjects. The treatment groups were acetaminophen 1000 mg, acetaminophen 1000 mg + codeine 16 mg + caffeine 30 mg and placebo. The results demonstrated that both active treatments were superior to placebo. Overall, the combination was slightly better than acetaminophen alone. The advantage of the combination appeared more evident in the "severe" baseline pain group.

Acetaminophen↗