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PubMed1993

Effects of codeine, naproxen and dexamethasone on formalin-induced pain in the naked mole-rat.

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.

Animals↗
PubMed1996

Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate.

We have performed a prospective randomised trial of 30 patients undergoing craniotomy to compare intramuscular codeine phosphate with patient-controlled analgesia using morphine 1 mg bolus with a 10-min lockout and no background infusion. For 24 h postoperatively, pain, nausea, Glasgow coma score, respiratory rate and sedation score were assessed. There was a wide variation in the amounts of morphine requested by the patients in the patient-controlled analgesia group in the first 24 h postoperatively (range 2-79 mg, median 17 mg). There was a small, but non-significant, reduction in pain scores in the patient-controlled analgesia group. There were no significant differences between the two groups in respect of nausea and vomiting, sedation score or respiratory rate. No major adverse effects were noted in either group. Patient-controlled analgesia with morphine is an alternative to intramuscular codeine phosphate in neurosurgical patients which merits further investigation.

Adolescent↗
PubMed1987

Effects of graded oral doses of a new 5-hydroxytryptamine/noradrenaline uptake inhibitor (Ro 15-8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in healthy men.

1. Ro 15-8081 (Hoffmann-La Roche, Basle, Switzerland) is a novel mixed 5-HT/noradrenaline uptake inhibitor producing potent antinociceptive effects in animal pain models. 2. In healthy man, two models with electrically and thermally induced pain, respectively, have been shown to reliably discriminate between the effects of opioid as well as of antipyretic analgesics and placebo. 3. This study investigated the effects of single oral doses of 10, 25, and 50 mg Ro 15-8081 in comparison with 60 mg codeine and placebo on threshold and tolerance to electrically induced pain and on threshold to thermally induced pain. Furthermore, the effects on psychomotor function, self-rated subjective feelings, and side effect profile were studied. 4. Twenty healthy males participated each in five experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised two series of measurements before and twelve after drug administration, carried out at 30 min intervals. 5. Ro 15-8081 produced marked elevations of threshold and tolerance to electrically and of threshold to thermally induced pain. The effects of all doses of Ro 15-8081 were significantly superior to those of placebo. Threshold and tolerance to electrically induced pain were not affected differently by the three doses of Ro 15-8081, whereas the threshold to thermally induced pain was elevated significantly more by 50 mg than by 10 and 25 mg Ro 15-8081. 6. Codeine 60 mg had a more rapid onset of action and greater maximal effects than Ro 15-8081.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ultra rush bee venom immunotherapy does not reduce cutaneous weal responses to bee venom and codeine phosphate.

BACKGROUND: The rapid administration of bee venom in cumulative doses exceeding the quantity contained in one bee sting is well tolerated by most of the patients during 3.5 h of ultra-rush bee venom immunotherapy (VIT). The mechanism of this tolerance is unknown. OBJECTIVE: The aim of the study was to verify the hypothesis that either slow mediator depletion of mast cells or blockade of their surface receptor mechanisms by increasing doses of allergen might be the major mechanisms of tolerance induced by ultra-rush VIT. METHODS: Nine bee venom allergic patients with a history of severe systemic reactions after a bee sting, positive skin tests and bee venom specific serum IgE antibodies were treated as follows: on the first day a cumulative dose of 111 micrograms was administered over 3.5 h under intensive care conditions. Further injections were given on day 7, day 21 and thereafter at 4 week intervals. Intradermal tests with codeine phosphate (non-specific mast cell degranulation) and bee venom were performed before the initiation of VIT and 30 min after the last injection on the same day as well as before the subsequent bee venom injections. RESULTS: No significant changes of skin reactivity to both codeine phosphate and bee venom were observed on day 1 (before initiation of VIT and after the last injection on the same day). CONCLUSIONS: Ultra-rush VIT does not induce mediator depletion or surface receptor blockade in skin mast cells.

Bee Venoms↗
PubMed1995

Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty.

The postoperative analgesic effect of ibuprofen was compared with a combination of ibuprofen and codeine versus placebo. The study was prospective, randomized, double blind with 123 consecutive hip arthroplasty operations. All the patients received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3-4 ml. Postoperatively, when the spinal anaesthesia started to wear off, the patients were randomly assigned to one of three groups; the ibuprofen group (n = 48) received 800 mg of ibuprofen orally. The ibuprofen/codeine group (IC, n = 48) received 800 mg of ibuprofen combined with 60 mg of codeine. The placebo group (P, n = 25), received oral placebo medication. The patients were observed for the need of additional opioid (e.g. ketobemidone), pain score (verbal and VAS), bleeding and side effects for five hours. The patients in the placebo group (P) had significantly higher pain scores (P < 0.05) compared with the two other groups after 2 and 4 hours, with no significant differences after 1, 3 and 5 hours. The P group also received 45% more opioids (P < 0.001) compared with the two other groups during the same period. No significant differences in bleeding or side-effects were observed between the groups. There were no significant differences between the ibuprofen group and the ibuprofen/codeine group. We conclude that a prophylactic dose of 800 mg ibuprofen orally has an opioid sparing effect with a tendency of less pain experience during the first hours after hip arthroplasty.

Administration, Oral↗
PubMed1982

A double-blind crossover study of the effect of loperamide hydrochloride and codeine phosphate on ileostomy output.

Loperamide hydrochloride (4 mg t.d.s.) was compared with codeine phosphate (60 mg t.d.s.) in a double blind crossover study of patients with loose output from their ileostomies. Both drugs significantly decreased the daily output and water content of ileostomy fluid. Daily losses of sodium and potassium were less when the patients were treated with loperamide. Loperamide was also associated with less side effects. It is concluded that loperamide hydrochloride was more effective in the treatment of ileostomy diarrhoea than codeine phosphate. In this group of patients those with the highest outputs from their ileostomies benefited most from this treatment.

Adult↗
PubMedDate not supplied

Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment.

It was investigated the in vivo effect of glutethimide on the intracellular neuroadaptation characteristic for m-opioid receptor tolerance induced by chronic codeine treatment and reflected by increased levels of adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA). AC activity was appreciated by cyclic-AMP (cAMP) formation, the levels of adenine and guanine nucleotides in brain extracts being assayed using a high performance liquid chromatographic method. The concomitant chronic administration of codeine and glutethimide resulted in a pronounced and long-lasting energetic depletion of the neurons, consistent with the high risk of overdose, and increase of cAMP's stable metabolite, 5'-AMP. This increase is persistent even after withdrawal and suggests an interference with the adenylyl cyclase system involved in the development of tolerance of opioid receptor and in relapse and provides a possible explanation of addiction and fast increase of doses observed in humans abusing this combination.

Adenylyl Cyclases↗
PubMed1986

Allergic urticarial rash from oral codeine.

A case of an urticarial rash from delayed-type allergy to orally administered codeine is presented. The literature on contact allergy to codeine is reviewed, and the rôle of patch testing in drug eruptions discussed.

Administration, Oral↗
PubMed1975

A rapid g.l.c. procedure for the determination of codeine and norcodeine in biological fluids based on micro-phase extraction techniques.

Therapeutic serum concentrations of codeine can be virtually completely extracted and obtained sufficiently concentrated for g.c. measurement without distillation, by acid extraction of the drug from the initial crude organic extracts of alkalinized serum followed by a micro-phase back extraction step. The procedure has simplicity, rapidity and eliminates concentration by distillation and background interference. The method can be readily adapted for the seperate measurements of codeine and norcodeine and it can also be used for similar analysis of other body fluids.

Body Fluids↗
PubMed1980

Self-association of analgesics in aqueous solution: association models for codeine, oxycodone, ethylmorphine and pethidine.

Light scattering, vapour pressure osmometry, conductivity and surface tension techniques have been used to examine aqueous solutions of several narcotic analgesics for evidence of association. Contrary to a previous report, no significant association could be detected in solutions of morphine sulphate and codeine phosphate. Other drugs which showed no evidence of aggregation in water included morphine hydrochloride, ethylmorphine hydrochloride, oxycodone hydrochloride and dihydrocodeine tartrate. Self-association of ethylmorphine hydrochloride, oxycodone hydrochloride and codeine phosphate was observed in the presence of 0.5 mol dm-3 electrolyte, the pattern of association conforming to that of a stepwise association process with all association constants of equal value. The association of pethidine hydrochloride in 0.5 mol dm-3 sodium chloride could be represented by an association scheme in which association constant KN increased sequentially with aggregation number N according to the relation KN = K(N - 1)/N.

Codeine↗
PubMed1979

Prostaglandin synthetase activity in acute ulcerative colitis: effects of treatment with sulphasalazine, codeine phosphate and prednisolone.

Prostaglandin synthetase activity in rectal biopsy specimens from patients with ulcerative colitis has been shown to fall on treatment with sulphasalazine, local steroids, and codeine phosphate. In vitro studies have shown that sulphasalazine is an inhibitor of prostaglandin synthetase, although less potent than indomethacin, whereas prednisolone and codeine phosphate were inactive. It is suggested that the therapeutic action of sulphasalazine may be related in part to its action in inhibiting prostaglandin biosynthesis.

Codeine↗
PubMed1988

Effect of codeine and loperamide on upper intestinal transit and absorption in normal subjects and patients with postvagotomy diarrhoea.

Patients with chronic severe diarrhoea after truncal vagotomy and pyloroplasty are often difficult to treat using conventional antidiarrhoeal drugs and remain severely disabled. We examined the effect of two drugs, codeine phosphate and loperamide, on upper intestinal transit and carbohydrate absorption, measured non-invasively by serial exhaled breath hydrogen monitoring, in patients with postvagotomy diarrhoea who had previously failed to gain relief from drug therapy. Orocaecal transit was consistently faster in these patients than a group of controls and was associated with malabsorption of glucose. Codeine phosphate 60 mg significantly delayed transit in patients and controls and was associated with a reduction in glucose malabsorption and improvement in symptoms. Loperamide also delayed transit and improved symptoms, but the doses required for this effect (12-24 mg) were higher than usually considered necessary in secretory diarrhoea. These studies indicate that rapid intestinal nutrient transit and associated malabsorption is a factor in the development of diarrhoea postvagotomy and that symptomatic relief can be achieved in most patients by more rational use of existing drugs.

Adult↗
PubMed1997

Pancreatitis induced by codeine: a case report with positive rechallenge.

A woman who developed acute pancreatitis following ingestion of low dose codeine, with positive rechallenge, is described. As this is the first case report of pancreatitis being induced solely by codeine, this side effect must be rare in view of the widespread consumption of this drug.

Acute Disease↗
PubMed1983

Oral analgesic efficacy of suprofen compared to aspirin, aspirin plus codeine, and placebo in patients with postoperative dental pain.

The purpose of this study was to evaluate the analgesic efficacy and safety of single oral doses of suprofen 200 and 400 mg, compared with aspirin 650 plus codeine 60 mg, aspirin 650 mg, and placebo in the relief of moderate to severe pain resulting from the surgical removal of impacted third molars. 157 patients completed a randomized, double-blind, single-dose, stratified, parallel-groups trial, and were observed for at least 4 h. Based upon each of the summary efficacy measures, sum pain intensity difference (SPID), percent SPID, TOTPAR and a global evaluation, all four active treatments were approximately equally effective and all were statistically superior to placebo. In addition, suprofen at both dose levels was significantly more effective than placebo beginning at the 0.5-hour observation for mean pain intensity, whereas the two aspirin treatments were not superior to placebo until the 1-hour observation. Side effects were minimal; there was one in the suprofen 200 mg, three in the aspirin 650 mg, and one in the placebo treatment group. Thus, it appears that suprofen at 200 and 400 mg is a safe and effective oral analgesic for the relief of moderate or severe postoperative dental pain, and it is possible that compared to aspirin 650 mg and aspirin 650 mg plus codeine 60 mg, it has a more rapid onset of action.

Adolescent↗
PubMed1994

The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects.

Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin-induced cough in 80 healthy volunteers (mean age 25 yrs). Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33 x 10(-4) M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces. The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit. These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances.

Adolescent↗
PubMed1985

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↗