Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Codeine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources

Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.

The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

Adolescent↗

Simultaneous determination of three opiates in serum by micellar liquid chromatography using direct injection.

A simple and reliable micellar liquid chromatographic method was developed for the simultaneous determination of 3 opiates (codeine, morphine, and thebaine) in serum, using direct injection and ultraviolet detection. The separation of the drugs was optimized on a C18 column, thermostatically controlled at 25 degrees C, by evaluating mobile phases containing sodium dodecyl sulfate (SDS) and various modifiers (propanol, butanol, or pentanol). Adequate resolution of the opiates was obtained with a chemometrics approach, in which retention was modeled as a first step by using the retention factors for several mobile phases. Next, an optimization criterion that takes into account the position and shape of the chromatographic peaks was applied. The 3 opiates were totally resolved and determined in 12 min with the mobile phase 0.15M SDS-7% (v/v) butanol buffered at pH 7. The limits of detection for codeine and morphine were greatly improved by using fluorimetric detection. Repeatability and intermediate precision were tested for 3 different concentrations of the drugs, and the relative standard deviations were <0.8% for most of the assays. Finally, the method was successfully applied to the determination of morphine and codeine in serum samples.

Algorithms↗

Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children.

(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.

Analgesics, Opioid↗

Potentially fatal paracetamol overdose and successful treatment with 3 days of intravenous N-acetylcysteine regime--a case report.

INTRODUCTION: Paracetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g. CLINICAL PICTURE: We describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L). TREATMENT: She was treated with a 3-day modified regimen of intravenous N-acetylcysteine. OUTCOME: The liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day. CONCLUSION: From this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.

Acetaminophen↗

Effects of sympathomimetic agents on opiate analgesia, tolerance and dependence in mice.

The effects of chronic pretreatment with ephedrine and phenylpropanolamine (PPA) on the antinociceptive activities of morphine and codeine, as well as their effects on the induction and expression of tolerance to, and dependence on morphine and codeine in mice are reported. Chronic pretreatment with ephedrine or PPA attenuated the antinociceptive effects of subsequently administered morphine or codeine. When administered during the induction phase, sympathomimetics enhanced opiate tolerance with little or no effect on the development of physical dependence. Given in the expression phase, ephedrine and PPA did not significantly affect tolerance, whereas there was significant suppression of withdrawal signs. The possible implications of these results are discussed.

Analgesia↗

Relationship between the antitussic and analgesic activity of substances.

The authors studied relationship between the antitussic and analgesic activity of substances. The antitussic effect of codeine, tilidine, tramadol and pentazocine has been studied in nonanesthetized healthy cats. The drugs except tilidine, were administered intraperitoneally in a dose of 10 mg/kg body weight. Tilidine was administered intramuscularly in the same dose. Cough induced in nonanesthetized cats by mechanical irritation of laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. A significant decrease of the subsequent cough parameters was observed after the application of codeine, tilidine, tramadol and pentazocine. Naloxone given 5 min before the application of the drug has not prevented the cough-suppressing effect due to codeine. Naloxone alone administered in a dose of 1 mg/kg body weight has not significantly influenced the experimentally-induced cough reflex in nonanesthetized cats.

Analgesia↗

Assessment and management of donor pain following marrow harvest for allogeneic bone marrow transplantation.

We studied the time course and intensity of pain of multiple bone marrow aspirations in 30 healthy adult marrow donors receiving acetaminophen with codeine for analgesia immediately after marrow harvesting for allogeneic bone marrow transplantation. Upon discharge, donors were supplied with acetaminophen (315 mg) plus codeine (30 mg) tablets and instructed to use one or two tablets up to every 4 h as needed for pain control. Donors used analgesic medication for a mean (+/- SE) of 3.3 +/- 0.5 days (range = 1-13 days) and reported less than complete pain relief. Subjects reported more pain at time of medication than between doses, indicating that the analgesic was at least partially effective. Male donors tended to report more pain and use more analgesic than did females. We conclude that donors self-regulate their analgesic usage to achieve maximal relief and that incomplete relief with acetaminophen plus codeine may be due to limited efficacy of this analgesic preparation. Our findings suggest that donor pain management may be improved by use of more powerful analgesics.

Acetaminophen↗

Differentiation between mu and kappa receptor-mediated effects in opioid drug discrimination: apparent pA2 analysis.

Apparent pA2 values for the opioid antagonist, quadazocine, were used to characterize differential involvement of mu and kappa opioid receptors in the discriminative stimulus effects of opioid agonists. Rhesus monkeys were trained to discriminate s.c. injections of either codeine or ethylketazocine from sham injections. In tests of drug generalization, morphine, levorphanol and alfentanil all produced dose-dependent increases in codeine-appropriate responding, and ethylketazocine produced dose-dependent increases in ethylketazocine-appropriate responding. Quadazocine antagonized the discriminative stimulus effects of each of the agonists. Apparent pA2 values for quadazocine (and slopes of the regression lines fit to the data in "Schild Plot" analysis) were 7.8 (-1.0) with morphine, 7.7 (-1.4) with levorphanol, 7.9 (-0.92) with alfentanil and 5.7 (-0.93) with ethylketazocine. If regression line slopes were constrained to equal -1, 7.8 was the apparent pA2 value with all agonists except ethylketazocine (5.7). This difference in apparent pA2 values for quadazocine confirms that different receptors (mu and kappa, respectively) mediate the discriminative effects of opioid agonists in codeine- and ethylketazocine-trained rhesus monkeys. Also, when the antagonism data were reanalyzed separately for each individual monkey, apparent pA2 values from individual animals were found to be similar to values from other animals in the same group and to values based on grouped data.

Alfentanil↗

GABA-ergic mechanisms in the central control of cough.

The antitussive activity of gabalinoleamide (Gabalid U CB) was studied in 40 non-anaesthetized cats. The antitussive action of the substance was compared to that of codeine (Codein Spofa). Cough was induced by mechanical stimulation using a chronic tracheal cannula. Single cough parameters were evaluated from changes in the side tracheal pressure. When gabalinoleamide was administered in a dose of 100 mg/kg b.w. intramuscularly all the studied parameters of cough showed a statistically significant decrease, only the intensity of maximum cough effort remained unaffected. Gabalinoleamide administered in the same dose induced a statistically significant decrease of respiratory frequency and breathing amplitude, and prolonged the cycle of breathing by delaying the expiratory phase. Higher doses (200 and 300 mg/kg b.w.) did not have an increased cough suppressing effect. The quality and quantity of cough parameters were similar after codeine and gabalinoleamide.

Animals↗

Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.

The influence of replacing the phenolic hydroxyl by the methoxy group on opioid receptor binding, analgesic and antitussive action was investigated in the corresponding couples morphine-codeine, hydromorphone-hydrocodone and O-desmethyltramadol (L 235)-tramadol. Binding was studied on rat whole brain membranes (without cerebellum) with the radioligands dihydromorphine (mu-site), ethylketocyclazocine (k-site), D-Ala2-D-Leu5-enkephalin (delta-site) and naloxone (no selective binding). Analgesia (tail flick) and antitussive action (NH3-vapour induced cough) was investigated in rats and ED50 values 10 min after i.v. application were calculated to compare efficacy. All free hydroxyl compounds had higher opioid receptor affinities than the corresponding methoxy derivatives and were more active at the mu-site. The methoxy derivatives codeine and tramadol only had low affinities lacking selectivity towards mu-, kappa-, or delta-binding. Hydrocodone in contrast showed strong and mu-selective binding. The hydroxy compounds had higher analgesic activity than the methoxy congeners and analgesia appeared to correlate with mu-binding affinity. Codeine and hydrocodone were weaker antitussives than the corresponding hydroxy compounds, whereas no significant difference was found between O-desmethyltramadol and tramadol. Only in the tramadol group the methoxy substitution increased antitussive potency in relation to analgesic potency.

Animals↗

A clinical trial in oral surgery of the analgesic efficacy of a suprofen/codeine combination.

Suprofen as well as codeine have been shown to be effective analgesics. In this study, a 200-mg suprofen/60-mg codeine dose is scored for analgesic efficacy and safety compared to suprofen (200 mg), codeine (60 mg), and placebo. One hundred sixty-five healthy, adult patients were asked to rate degree of pain experienced over a six-hour period after medication. The combination treatment was found to offer maximum pain relief. Dentists should be aware that flank pain and renal function abnormalities have been reported in postmarketing surveillance.

Adult↗

Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats.

The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.

Analgesics, Opioid↗

Central action of narcotic analgesics. VIII. The effect of dopaminergic stimulants on the action of analgesics in rats.

We investigated the influence of apomorphine, amphetamine, amantadine, dimethylaminoadamantane, nomifensine, ergometrine and beta-phenylethylamine on cataleptogenic and antinociceptive action of analgesics in rats. Nomifensine, apomorphine, beta-phenylethylamine, amantadine and ergometrine antagonized the catalepsy induced by morphine and codeine. Catalepsy induced by fentanyl was depressed only by nomifensine and apomorphine. Amphetamine only slightly antagonized the analgesic-induced catalepsy and the effects were not dose-dependent. Dimethylaminoadamantane did not antagonize catalepsy at all. Antinociceptive action of morphine and codeine was antagonized by apomorphine and amphetamine. Ergometrine counteracted the action of morphine, and beta-phenylethylamine decreased the action of pentazocine. The results suggest that: 1. There are differences in the mechanism of cataleptogenic action of the opiates (morphine and codeine) and fentanyl; 2. Catalepsy after analgesia differs from the catalepsy produced by neuroleptics in respect of interaction with such drugs as amphetamine, apomorphine or dimethylaminoadamantane. Analgesic-induced catalepsy seems to depend on the presynaptic inhibition of dopaminergic neurotransmission; 3. Stimulation of the central dopaminergic system in rat brain either does not change or weakly antagonizes the action of analgesics in the hot plate test.

Amphetamine↗

[Assessment of morphine-type physical dependence liability in mice using the drug-admixed food method].

Physical dependence on morphine-type drugs (morphine, codeine and pethidine) in mice were examined by the drug-admixed food method. Mice were treated with drug-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. Morphine- and codeine-treated mice showed withdrawal signs when they were given naloxone (5 mg/kg, s.c.), while pethidine-treated mice did not show the withdrawal signs. However, mice treated with pethidine-admixed food (1-6 mg/g food) for 28 days showed naloxone precipitated withdrawal signs. Thus, the data obtained with mice indicate that pethidine produces a weak physical dependence. On the other hand, codeine (40 mg/kg, s.c.) and pethidine (100 mg/kg, s.c.) administration suppressed the abrupt withdrawal signs of morphine-dependent mice that were treated with morphine-admixed food, while the withdrawal signs were completely suppressed in mice administered only 5 mg/kg morphine. These results suggest that the physical dependence liability of morphine type drugs can be predicted by the drug-admixed food method.

Administration, Oral↗

Kinetics of 11C-labeled opiates in the brain of rhesus monkeys.

The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

Animals↗

Urinary sex-dependent low molecular weight proteins as a sign of narcotic dependence in male rats.

The relationship between urinary excretion of sex-dependent low molecular weight proteins (LMWP) in male rats and narcotic dependence has been investigated in this study. Chronic administration of codeine (0.5 mg/g food) caused a significant decrease in urinary excretion of LMWP from the third day, without any change in urinary high molecular weight proteins. The decrease recovered to the control level after the withdrawal of codeine. Withdrawal symptoms including loss of body weight and diarrhea were observed following codeine withdrawal. In animals chronically treated with pethidine (1.0 mg/g food), however, neither changes in urinary LMWP excretion nor withdrawal symptoms were observed. These present findings suggest that the decrease in urinary excretion of sex-dependent LMWP is related to narcotic dependence in male rats, since we previously reported the decrease in urinary excreted LMWP in morphine-dependent rats.

Albuminuria↗

Cholinergic influences on opioids activity in rats.

The influence of cholinergic and anticholinergic agents on the catalepsy and antinociceptive action of morphine, codeine, fentanyl and pentazocine was studied in rats. Anticholinergic drugs scopolamine (3 and 6 mg/kg) and slightly atropine (1 mg/kg) enhanced morphine-induced catalepsy. Benztropine did not change this action of morphine. Cholinergic physostigmine (0.2 and 0.4 mg/kg) showed marked and dose-dependent antagonism toward morphine catalepsy, but pilocarpine, in doses of 2 and 4 mg/kg, failed to influence it. Catalepsy induced by codeine and fentanyl was nearly not influenced by cholinergic and anticholinergic agents. In the hot plate test, cholinergic influences on antinociceptive activity of analgesics are slight, but sometimes it may be observed the similar interaction as in morphine catalepsy: anticholinergic agents enhance, and cholinergic agents antagonize these effects. Present results indicate that some cholinergic and anticholinergic agents influence morphine catalepsy, and this influence is opposite to that observed in neuroleptic-induced catalepsy. Failure of the cholinergic influences on fentanyl- and codeine-induced catalepsy suggests that the mechanisms of cataleptogenic activity of morphine and other analgesics are not the same.

Analgesia↗

Double-blind study of glaucine in chronic cough.

Thirty-eight patients, affected by chronic cough and hospitalized in 14 different rooms, entered a double-blind cross-over trial aimed at evaluating efficacy and tolerance of single oral doses of glaucine (eo mg) versus single oral doses of codeine (30 mg) and placebo. Patients occupying the same room were administered on 3 consecutive nights, and an objective evaluation of efficacy was ensured by means of a tape recorded. The mean cough counts during the 8-h interval after drug administration were 269.3 after placebo, 241.8 after glaucine, and 201.9 after codeine (p less than 0.05). The antitussive effects of glaucine and codeine were practically superimposable up to the 6th h, when glaucine effect declined. Treatments were well tolerated by all the patients, they themselves were not able to detect any difference in cough suppression among the three treatments.

Antitussive Agents↗