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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↗

PubMedDate not supplied

Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

Codeine↗

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↗

PubMed1998

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↗

PubMed2005

Co-consumption of benzodiazepines in heroin users, methadone-substituted and codeine-substituted patients.

Concomitant consumption of benzodiazepines (BZDs) and opioids is a major problem in patients with opioid dependence. It may have substantial impact on morbidity, mortality and clinical course. The current retrospective study aims to determine whether there are differences in the additional use of BZDs among addicts regularly taking methadone or codeine medications in treatment and untreated addicts injecting heroin. The records of 1,685 patients admitted for detoxification were analyzed using bivariate analysis and multiple logistic regression analysis. Demographic and drug related variables were considered, both as possible confounders and predictors of concomitant BZD use. Daily intake of BZDs was reported in 44.4% of the patients. Patients treated with methadone or codeine medications report daily intake of BZDs significantly more often than the heroin-dependent patients (p < 0.01). Using multiple regression analyses, the results were confirmed as independent from the assessed possible confounders. Further we found that daily use of alcohol or barbiturates, early onset of opioid use (p < 0.01), unemployment, having a substance dependent family member with, and a history of imprisonment (for all p < 0.05) were associated with concomitant daily consumption of BZDs in opioid dependent subjects. These finding underline the need to further explore the causes, interactions and consequences of concomitant BZD and opiate use.

Adolescent↗

PubMed1977

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↗

PubMed1999

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↗

PubMed2003

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↗

PubMed1980

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↗

PubMed1990

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↗

PubMed1999

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↗

PubMed2002

[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↗

PubMed2004

Endogenous morphine and codeine in the brain of non human primate.

BACKGROUND: Morphine is the most used compound among narcotic analgesics. Apart from its presence in the poppy plant, morphine has been shown to be endogenously present in different tissues of mammals and lower animals. MATERIAL/METHODS: The presence of endogenous morphine and codeine was investigated by Gas Chromatography/ Mass Spectrometry (GC/MS) in the brain of non human primate. The release of endogenous morphine from monkey brain slices was studied in vitro in the presence of high potassium concentrations with and without calcium in the medium. RESULTS: Endogenous morphine, and its direct precursor codeine, was for the first time detected by GC/MS in the brain of non human primate. High potassium concentrations depolarized neurons releasing endogenous morphine twofold above basal line levels in a calcium dependent mechanism. CONCLUSIONS: This finding confirms the presence of the endogenous alkaloid throughout the phylogenesis of the nerve system of mammals and lower animals and indicates that endogenous morphine might function as a neuromodulator/neurotransmitter agent in the central nervous system (CNS) of non human primates.

Animals↗

PubMed2004

A case of probable codeine poisoning in a young infant after the use of a proprietary cough and cold medicine.

We report a case of probable poisoning with codeine phosphate in a 3-month-old infant, which was associated with excessive dosing and concomitant use of antihistamines. Investigation into the patient's drug history identified the recent use of a proprietary cough and cold medicine containing codeine phosphate and dexchlorpheniramine. The prescribing information, available from a popular prescribing handbook, listed only one dosage for children, without any adjustment for age or size, and did not bear any warning for its use in young children. A review of the handbook identified seven additional remedies that were similarly listed. Medical practitioners and pharmacists should be aware of this prescribing pitfall. Improvements are needed in the prescribing information pertaining to the use of cough and cold formulas containing opioid or opioid-like antitussives among young children, and clear warnings should be included in drug inserts and formularies.

Antitussive Agents↗

PubMed1992

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↗

PubMed1999

[Determination of diclofenac sodium and codeine phosphate in shuerfen tablets by CPA-matrix method].

The contents of diclofenac sodium and codeine phosphate in shuerfen tablets may be determined simultaneously by CPA-matrix method without separation of its components. The program was edited by BASIC. The average recoveries and RSD were 99.85%, 0.46% for diclofenac sodium and 99.80%, 0.50% codeine phosphate, respectively. This method is simple and rapid, and the result is accurate.

Codeine↗

PubMed1991

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↗