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PubMed1990

[Double blind biometric study on postoperative effects of analgesics].

A double blind trial to study the effects of analgetics was carried out in patients suffering from pain after third molar osteotomy. 204 patients were evaluated after random allocation to treatment with paracetamol 500 mg and paracetamol 500 mg plus codeine 30 mg. Statistical evaluation revealed a tendency for better analgesia using the combination of paracetamol and codeine. For further studies an exact stratification for sex and age is necessary. Sample sizes of 150 patients are necessary for each parameter.

Acetaminophen↗
PubMed1990

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Adult↗
PubMedDate not supplied

Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics.

The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors.

Analgesics, Opioid↗
PubMed1989

[Cancer pain management].

Pain, the most frequent subjective symptom in cancer patients, can and must be treated. Satisfactory pain relief helps whatever patients achieve their remaining potential. This transforms his experience and the memories of his family. Management of pain becomes the physician's primary objective if there is no available treatment for the cause of pain. The use of analgesic drugs is the mainstay in cancer pain management. When used correctly, analgesics are effective in a high percentage of cancer patients. This approach can be implemented in all medical settings and serves to improve quality of life in far-advanced cancer patients. A three-step analgesic ladder indicating the sequential use of the drugs was proposed by the World Health Organization (WHO) in 1986. The three standard analgesics making up this ladder are aspirin (non-opioid), codeine (weak opioid) and morphine (strong opioid). In patients with mild pain, non-opioid drugs such as aspirin, acetaminophen, or any of the non-steroidal anti-inflammatory drugs will be adequate. In patients with moderate pain, if non-opioids do not provide adequate relief, codeine or an alternative weak opioid should be prescribed. In patients with severe pain, morphine, a strong opioid, is the drug of choice. A series of principles established on the basis of considerable clinical experience and of controlled studies of analgesics indicate that the dose of an analgesic should be determined on an individual basis, and administered on a regular basis by the clock.

Analgesics↗
PubMed1988

Antitussive properties of levodropropizine.

The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols.

Administration, Oral↗
PubMed1987

Opiates in poppy seed: effect on urinalysis results after consumption of poppy seed cake-filling.

We report the analysis of poppy seed filling for morphine and codeine content. Concentrations in the range 17.4 to 18.6 micrograms/g (morphine) and 2.3 to 2.5 micrograms/g (codeine) were found in different lots of the filling, which is widely used in baking. The effect of consumption of poppy seed filling on opiate urinalysis results is discussed. Morphine concentrations as high as 4.5 mg/L are reported, with persistence of concentrations greater than 0.3 mg/L as long as 35 h after consumption.

Chromatography↗
PubMed1987

Effects of antitussive drugs under normal and pathological conditions.

The antitussive effect codeine and 1-propoxyphene have been studied in non-anaesthetized healthy cats and cats with respiratory tract inflammation elicited by undiluted croton oil. The drugs were administered intraperitoneally in doses of 10 and 20 mg/kg body weight. The antitussive effect was studied on the 4th day, after inflammation had set in. Cough induced in nonanaesthetized cats by mechanical irritation of the laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. Experimentally induced inflammatory changes of the respiratory tract due to the antitussive activity of 1-porpoxyphene were significantly reduced, but that of codeine had not changed at all.

Animals↗
PubMed1985

Postextraction pain relief in children: a clinical trial of liquid analgesics.

Our objective was to evaluate the relative efficacies of four liquid analgesics in children, five to twelve years of age, following dental extractions. The analgesics, acetaminophen elixir (240 or 360 mg), acetaminophen with codeine elixir (240 mg and 24 mg, respectively), aluminum ibuprofen suspension (200 mg), and placebo liquid were administered at home, as a single dose, in a randomized double-blind study design. Of the 154 patients enrolled, 45 were evaluated, 39 patients never required medication, 12 were lost to follow-up, and 8 were excluded for other reasons. Aluminum ibuprofen provided significant relief in one-half hour compared with placebo. At one hour, both aluminum ibuprofen and acetaminophen with codeine provided significant relief compared with placebo. All three active agents were effective at two hours. The global rating of drug efficacy was statistically superior for aluminum ibuprofen. The majority of patients in all four groups were pain-free after four hours. No adverse reactions were reported during the study.

Acetaminophen↗
PubMed1977

Reinforcing properties of perphenazine, haloperidol and amitryptiline in rhesus monkeys.

Possible negative reinforcing effects of perphenazine, haloperidol and amitryptiline were studied in rhesus monkeys previously trained to avoid electric shock by responding. Responding extinguished a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the light was switched on. A response occurring when the light was on switched the light off for a period of 1 minute (time-out period). a response during the infusion terminated the infusion. Under these conditions, the monkeys tolerated a large number of saline infusions. Saline was replaced by different doses of perphenazine, haloperidol and amitryptiline, each for 12 successive daily 2-hour sessions. Infusions of perphenazine (0.50-1.6 microng/kg) and to a lesser extent infusions of haloperidol (2.5 microng/kg) generated and maintained responding. Most of the infusions of amitryptiline in the dose range of 1.0 to 10.0 microng/kg were tolerated. Haloperidol and perphenazine in doses higher than 10.0 micmitryptiline (500-3000 microng/kg i.v.) had no influence on shock avoidance behavior. Positive reinforcing effects of these compounds were studied in a group of monkeys trained to respond under a 10 response fixed ratio of intravenous infusions of codeine. None of the three compounds maintained responding previously engendered by codeine.

Amitriptyline↗
PubMedDate not supplied

Central action of narcotic analgesics. V. Participation of serotonin in the mechanism of action of narcotic analgesics.

The influence of serotonergic system on the changes in locomotor activity of mice and rats brought about by morphine, fentanyl, codeine and pentazocine and on morphine induced catalepsy in rats was studied. p-Chlorophenylalanine (pCPA) did not affect the behavioral changes produced in mice by morphine, fentanyl, codeine and pentazocine but reduced the behavioral depression produced by these drugs in rats. 5-Hydroxytryptophan (5-HTP) but not tryptophan (TP) reversed the action of pCPA on the effect of morphine and fentanyl. After reserpine the depression produced in rats by morphine and fentanyl was more pronounced. TP did not change the depression produced by combination of reserpine and morphine but counteracted the depression observed after combination of reserpine and fentanyl. In mice reserpine protected against hypermotility produced by morphine or fentanyl and TP potentiated the depression produced by the combination of reserpine and morphine or reserpine and fentanyl. Serotonin precursors, 5-HTP and TP evidently potentiated the morphine induced catalepsy. pCPA counteracted only the enhancement of the catalepsy observed after TP administration. Naloxone abolished the catalepsy after combined treatment with morphine and TP. Similarly but weaker acted cyproheptadine. The results suggest that the serotonin system plays a role in the effects of morphine and fentanyl on rat locomotor activity. An increase in the cerebral serotonin level increases the morphine catalepsy in rats.

Analgesics, Opioid↗
PubMed1979

High pressure liquid chromatographic determination of the five major alkaloids in Papaver somniferum L. and thebaine in Papaver bracteatum Lindl. capsular tissue.

A high pressure liquid chromatographic isocratic procedure is described for determining and quantitating the 5 major alkaloids narcotine, papaverine, thebaine, codeine, and morphine in Papaver somniferum L. and thebaine in Papaver bracteatum Lindl. Other papaveraceous alkaloids, including salutaridine, oripavine, laudanosine, isothebaine, cryptopine, alpinigenine, narceine, protopine, and gnoscopine, were also quantitated. The values for morphine, codeine, and thebaine in P. somniferum were in agreement within 5--9% with values obtained by the United Nations Narcotics Laboratory by other methods. In contrast to previously reported procedures, the advantage of this method is that no precolumn or other purification other than solvent extraction of the capsular tissue is necessary. Isocratic chromatography alone on a single column resolved the 5 major alkaloids.

Chromatography, High Pressure Liquid↗
PubMed1983

[Difference in the effects of antitussive drugs on respiration and cough reflex].

In order to understand the relationship between the cough and respiratory centers in the brain stem, we investigated the effects of antitussive drugs such as codeine, dextromethorphan, eptazocine and fominoben on respiratory movement and the cough reflex. Coughs were induced using electrical stimulation of the central cut end of the right superior laryngeal nerve in lightly anesthetized dogs. The drugs were administered intraarterially into the vertebral artery. Rate (RR), amplitude (RA) and volume (RV) of the respiration and number (NC) and amplitude (AC) of the cough reflex evoked were measured as indices. Codeine produced a decrease in RR, RV and NC at 0.3 mg and, additionally, AC at 1 mg. Dextromethorphan increased RR and RV and rather enhanced NC and AC at 0.3 mg, but the agent reduced NC and AC at 3 mg even if it increased RR and RV. Eptazocine produced decreases in RA, NC and AC at 1 mg, and, additionally, RV at 10 mg. Fominoben increased RR, RA and RV dose-dependently at 0.3-3 mg, although it depressed NC and AC at 3 mg. These findings suggest that the thresholds for the cough responses and respiratory responses to antitussive drugs are different from drug to drug and that the respiratory centers and cough center in the brain stem are affected in a different manner even qualitatively.

Analgesics↗
PubMed1983

Assessment of antitussive effects by citric acid threshold.

The cough threshold to citric acid inhalation was measured in eight subjects by single inhalations of increasing concentrations of citric acid until a cough was consistently produced. The cough threshold was measured before and after 60 mg glaucine, 60 mg codeine and matched placebo on three separate days a week apart. Base-line cough threshold in each subject was consistent from week to week. Codeine increased the threshold by more than one citric acid concentration in three subjects. Placebo and glaucine did not produce a threshold change of more than one citric acid concentration. We conclude that the citric acid threshold is a simple measure of antitussive activity. No such activity was found with glaucine.

Adult↗
PubMed1983

Does non-immunologic mast cell mediator release/activation elicit a late cutaneous response?

Early wheal responses to intracutaneous codeine injection have virtually no tendency to proceed to late cutaneous responses in normal subjects and patients with chronic urticaria. This finding is taken to indicate that the transient burst of mast cell mediator release/activation in a quantity sufficient to elicit a sizable early response may not, by itself, fulfill conditions required to lead to late cutaneous allergic responses. In patients with angioedema and a recent requirement for steroid therapy early wheals followed by small late cutaneous responses were elicited by codeine and histamine. This effect by histamine, not observed in normals, indicates a unique host susceptibility to prolonged responses in these individuals. The inhibition of these small late responses by ingested prednisone may be representative of the mechanism of therapeutic efficacy of the drug in these cases.

Angioedema↗
PubMedDate not supplied

A method for the 12-hour evaluation of analgesic efficacy in outpatients with postoperative oral surgery pain. Three studies of diflunisal.

We have developed a method for measuring the efficacy of a single dose of an analgesic for 12 hours after administration of outpatients with postoperative oral surgery pain. Using a self-rating record, patients evaluate their pain and its relief for 12 hours after medication. We have used this method successfully in a series of three studies to compare diflunisal, a new nonsteroidal antiinflammatory analgesic, with placebo and aspirin 650 mg, acetaminophen 600 mg, propoxyphene napsylate 100 mg, or a combination of acetaminophen with either codeine 60 mg or propoxyphene 100 mg. Diflunisal evinced an unusually long duration of analgesic effect. In each study, all doses of diflunisal were significantly superior to placebo through the end of the 12-hour observation period, while the standards were superior for periods ranging from 2 to 7 hours. In terms of peak analgesia, diflunisal 1,000 mg was comparable to the acetaminophen-codeine combination and was significantly superior to all the other analgesic standards.

Acetaminophen↗
PubMed1981

An evaluation of the analgesic efficacy of three opioid-analgesic combinations in postoperative oral surgery pain.

The analgesic efficacy of a hydrocodone-acetaminophen combination, a codeine-acetaminophen combination, a codeine-APC (aspirin, phenacetin, and caffeine) combination, and a placebo was evaluated in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Each of the active medications had a significant effect on essentially all measures of total and peak analgesia; they did not differ significantly on any measure of analgesia. Adverse effects were transitory and, in general, appear to have been related to the centrally acting component of each combination analgesic.

Acetaminophen↗
PubMed1980

Relief of postoperative pain by ibuprofen: a report of two studies.

The value of ibuprofen (Motrin) as an analgesic was assessed in two consecutive studies in 425 patients with postherniorrhaphy pain. In the first study, 400 mg ibuprofen proved superior to placebo and as effective as one tablet of a compound containing 375 mg of acetylsalicylic acid, 30 mg caffeine and 8 mg codeine (ACC-8). In the second study, the analgesic effectiveness of 400 mg of ibuprofen was intermediate between that of two tablets of ACC-8 and one tablet of ACC-30 (a compound containing 375 mg ASA, 30 mg caffeine and 30 mg codeine). The side effects of all drugs were negligible. Ibuprofen should be a suitable alternative analgesic in postoperative pain of this type.

Adolescent↗
PubMed1982

A model of clinical pain. Technique for evaluation of analgesic agents.

A method is described utilizing repetitive electrical stimulation for the production of long-term continuous pain which approaches the quality of clinical pain. This technique provides for on-line monitoring of actual power delivered to the subject. Incremental stimuli of high and low intensities were randomly superimposed on continuous painful background electrical stimulation. Subjects were studied in a triple crossover design with acupuncture, codeine and baseline treatments. Data were evaluated by Sensory Decision Theory (SDT) procedures. The codeine compound significantly raised the response criterion to higher intensity stimuli but did not effect perception of low intensity stimuli, indicating an analgesic but not an anesthetic effect. No significant differences were found between control and acupuncture results for either pain discriminability or pain report criterion. The results are discussed with regard to the physiological effects of electrical stimulation and the merits of this new stimulation technique.

Acupuncture Therapy↗