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Comparison of diflunisal and acetaminophen with codeine in the treatment of mild to moderate pain due to strains and sprains.

Fifty college athletes with acute sprains and strains from football-related activities were randomly assigned to treatment with either diflunisal or acetaminophen with codeine for seven days. Additional treatment in both groups included rest, elevation, local application of cold or heat, splinting, and physical therapy, as indicated. Both treatment groups exhibited clinically significant improvements in pain, tenderness, and swelling. The results of this study show that diflunisal, a peripherally acting nonnarcotic nonsteroidal anti-inflammatory agent with analgesic properties, was as effective as acetaminophen with codeine in relieving mild to moderate pain due to musculo-skeletal sprains and strains. The long duration of action of diflunisal permits less frequent dosing, an important consideration when prescribing medication for active young adults.

Acetaminophen↗

Efficacy of diflunisal versus acetaminophen with codeine in controlling mild to moderate pain after arthroscopy.

An open, randomized clinical study was performed to evaluate the efficacy of diflunisal versus acetaminophen with codeine in patients who underwent outpatient arthroscopy of the knee. Twenty patients were randomly assigned to each treatment group. Nineteen patients in each group successfully completed the study, which consisted of both objective and subjective evaluations. The results showed equal efficacy between the two drugs. However, a larger percentage of patients viewed diflunisal as providing good to excellent results overall compared with acetaminophen with codeine.

Acetaminophen↗

Deaths as a result of a combination of codeine and glutethimide.

Toxicological findings are described in 16 medical examiner cases directly related to the combination of codeine and glutethimide. The cases described represent a six-month period, July through December 1982, showing the epidemic rate of abuse of this drug combination, most prominent in the Newark, NJ area since the late 1970s. Concentrations of codeine and glutethimide, measured by gas liquid chromatography (GLC), in the blood averaged 0.62 and 4.07 mg/L, respectively. Similarly determined urine concentrations averaged 38.06 and 12.68 mg/L, respectively. Specific concentrations of each drug in most cases were in the high therapeutic range, suggesting a possible toxic synergistic effect.

Adult↗

Codeine and its alternates for pain and cough relief . 4. Potential alternates for cough relief.

In this report-the fourth of a series on codeine and its alternates for pain and cough relief-an attempt is made to evaluate, on the basis of experimental and clinical data, and wherever possible in comparison with codeine, the effectiveness of a number of antitussive substances currently in clinical use. In the discussion of the undesired side-effects particular attention is paid to the risk of dependence and abuse.

Alkaloids↗

Codeine and its alternates for pain and cough relief. 2. Alternates for pain relief.

This report-the second of a series on codeine and its alternates for pain and cough relief-contains a detailed evaluation of experimental and clinical data on newer substances having analgesic properties comparable to and in approximately the same range as those of codeine. The data are discussed under the headings: analgesic effects in animals; clinical usefulness; side-effects with particular reference to dependence and abuse liability.

Amides↗

Codeine and its alternates for pain and cough relief. 5. Discussion and summary.

This chapter concludes the survey of experimental and clinical data on the analgesic and antitussive properties of codeine and its potential therapeutic alternates. From an evaluation of their effectiveness on the one hand and the side-effects, including tolerance, dependence and abuse liability on the other, it would appear that the therapeutic goals of codeine could be achieved by other substances, except perhaps where analgesia, cough relief, and sedation are required simultaneously. The use of these other substances would, however, result in no particular gain and probably no particular loss.

Analgesics↗

Chenodeoxycholic acid-induced diarrhea in rats: effects of atropine and codeine.

Orally administered chenodeoxycholic acid (300 mg/kg) produced diarrhea and accumulation of gastro-intestinal fluid in rats. The fluid in the stomach and small intestine remained accumulated even after the accumulated colonic fluid and the diarrheal excretion decreased. When instilled into an intestinal closed-loop, chenodeoxycholic acid caused a marked inhibition of fluid absorption in the colon and jejunum but less effect in the ileum. On the contrary, an intravenous administration of chenodeoxycholic acid caused neither diarrhea nor impairment of colonic absorption of fluid. Atropine and codeine (10 mg/kg s.c.) blocked or at least delayed the diarrhea produced by oral administration of chenodeoxycholic acid. The antidiarrheal activity of codeine was found to be more potent and longer-lasting than that of atropine. Both drugs delayed the passage of chenodeoxycholic acid containing gastric fluid into the duodenum, but neither of them prevented chenodeoxycholic acid-induced jejunal secretion of fluid and electrolytes. These results indicate that the diarrheal excretion by chenodeoxycholic acid was ascribable to the impairment of fluid absorption in the colonic mucosa and partly to the activation of gastro-intestinal propulsive motility.

Analgesia↗

[Urticarial skin reaction to codeine, a measure of mast cell reactivity].

The reactivity of skin mast cells was tested in 86 probands. Introduction of various concentrations of codeine phosphate, either by intradermal injection or by prick test, produced an immediate wheal and flare response. Since the codeine skin test depends on both release of and response to histamine, it may be more useful than the conventional skin test with histamine for assessment of skin reactivity, and also for preliminary evaluation of anti-allergic agents in man.

Codeine↗

A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.

The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double-blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.

Acetaminophen↗

Naproxen sodium vs. a combination of aspirin, phenacetin, caffeine and codeine phosphate for pain after major gynecologic surgery. A multicenter comparison.

In this multicenter study a nonnarcotic analgesic available for moderate pain, naproxen sodium, 550 mg, was compared to a combination that is used extensively for moderate to severe pain, aspirin, phenacetin, caffeine and codeine phosphate (APC/C) (60 mg of codeine phosphate). Women with pain after major gynecologic surgery reported a similar pattern in pain reduction with the two medications except for a relatively sharper increase in pain intensity between four and six hours after administration of APC/C. A smaller number of patient complaints suggested that naproxen sodium was better tolerated than APC/C.

Aspirin↗

[Short-term therapy of painful muscular disorders. Results of a multicenter double-blind test of 2 new suppository preparations with and without codeine].

A report is given about a multicentric double-blind test for proof of effectiveness of two new suppository preparations with and without codeine against comparable remedies. Dolo Visano Supp. sine codeino showed a slight superiority over the reference preparation. This was proved above all for the influence upon pain and muscular overstrain. The better tolerability was marked. Dolo Visano Supp. (with codeine) showed advantages against the reference preparation. It was used in cases of severe pain, and in 88% it had a very good effect, whereas for the reference preparation this applied only in 67,9%. The assessments of physician and patients were almost alike. The myotonolytic effect has been proved equally for both of the new suppository preparations.

Arthritis↗

[Covalent binding of codeine hydroxylation products to albumin and microsomal membranes].

It was shown that incubation of rat liver microsomes with [3H] codeine in the presence of 3 mM NADPH and 0.5% albumin is accompanied by covalent binding of codeine radioactive metabolites to albumin and microsomes. At low concentrations of the microsomal protein in the samples the number of metabolites bound to the membranes is greater than those bound to albumin. At increasing concentrations of the microsomal protein the binding occurs mainly at the expense of albumin. The animal induction with phenobarbital increases the number of bound metabolites. An injection of 3-methylcholantrene does not affect the degree of binding. All typical inhibitors of cytochrome P-450, i.e. SKF-525A, methyrapone, octylamine and CO, inhibit the binding. The data obtained suggest that the metabolites which bind to the macromolecules are generated by cytochrome P-450. It is assumed that the appearance in the blood of covalently bound albumin-hapten conjugates formed in the cytochrome P-450--hydroxylase system can induce the immune response. Hense, one more protective system of the organism becomes involved in the decontamination of low molecular weight compounds.

Albumins↗

[Drug substitution treatment of heroin dependent patients with codeine preparations--treatment effects from the viewpoint of the physicians and patients].

The controversy caused by the debate on treatment and substitution strategies in drug addiction is unchanged. This is particularly true concerning the use of codein-based drugs in the substitution of heroin abusers. However, only a few studies on the effects of this old and widely used method of substitution have been carried out. This article presents one retrospective and prospective study on the effects of the codein-based substitution in heroin abusers (n = 416). With respect to the issues addressed by this study such as somatic and psychic health, social integration, delinquincy and consumption patterns, patients as well as clinicians report an improvement in general health and fewer of the problems usually associated with heroin abuse, similar to the results from substitution treatment elsewhere.

Adult↗

Potential synthetic codeine substitutes: (-)-3-O-aryl-N-methylmorphinans.

A series of novel O-aryl-N-methylmorphinans (7-19) were synthesized by the Ullmann reaction from levorphanol (4) in our search for a synthetic codeine (2) substitute with reduced addition liability. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, (-)-3-phenoxy-N-methylmorphinan (7) is an orally active analgesic comparable in potency to codeine (2), which exhibits decreased physical dependence liability and longer duration of action.

Animals↗

Partial filling micellar electrokinetic chromatography optimization studies of ibuprofen, codeine and degradation products, and coupling to mass spectrometry.

Studies have been performed to evaluate whether an on-line partial filling-micellar electrokinetic chromatography (PF-MEKC) system could be applied to a recently developed MEKC method for the separation of ibuprofen, codeine and one of the degradation products. Attempts to couple the PF-MEKC system to MS have also been performed. SDS concentration, micellar zone length and concentration of acetonitrile in the buffer were optimized using factorial design. When a small micelle zone was injected directly after the sample introduction, the results improved markedly. The MS parameters have not been optimized, but the studies show promising results for the use of PF-MEKC-mass spectrometry for identification of the degradation products.

Acetonitriles↗

Partial filling-micellar electrokinetic chromatography optimization studies of ibuprofen, codeine and degradation products, and coupling to mass spectrometry: part II.

We describe the use of partial filling-micellar electrokinetic chromatography-mass spectrometry (PF-MEKC-MS) on the pharmaceutical ingredients ibuprofen and codeine phosphate as well as their degradation products and impurities. The study focuses on the change of the borate buffer to the volatile ammonium acetate and the optimization of critical MS parameters. The sensitivity of the method is also evaluated. The results are compared to an existing MEKC-UV method that is used for quantitative determination of the two main substances as well as for the analysis of the degradation products. It is concluded that the PF-MEKC-MS system is suitable for separation and identification.

Acetates↗

Analgesic comparison of propiram fumarate with pentazocine, codeine, and placebo in postsurgical pain.

The safety and effectiveness of a single oral dose of 50 mg propiram fumarate as an analgesic was compared in a double-blind clinical trial trial against single doses of standard reference analgesics (50 mg pentazocine hydrochloride or 60 mg codeine sulfate) or placebo. Subjects were adult patients experiencing severe postsurgical pain. Mean pain scores and SPID scores showed all three active drugs to be favored (P less than 0.05) over placebo in patients with severe initial pain. The most common side effects seen were drowsiness, nausea, and dizziness. These were not severe enough to require treatment. Propiram fumarate (50 mg) was shown to be an effective and safe analgesic in the treatment of severe postsurgical pain.

Adolescent↗