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PubMed2006

Treatment of pain during medical abortion.

A structured literature review was undertaken to determine, in the context of early medical abortion, the proportion of women who require analgesia, the predictors of analgesia requirement and the most appropriate analgesia regimen. Studies from different centers show wide variations in analgesia use, but, overall, around 75% of women use narcotic analgesics on the day of prostaglandin administration. Differences are likely to be due to differences in policies for offering analgesia rather than differences in patient characteristics. The following characteristics are consistently associated with increased requirement for analgesia: increasing gestation, younger patient age, nulliparity and White race. A regimen comprising 325-500 mg of paracetamol (acetaminophen) with 10 mg of dihydrocodeine or 30 mg of codeine has been used by thousands of women without apparent problems.

Abortion, Induced↗
PubMed2003

Optimized conditions for simultaneous determination of opiates, cocaine and benzoylecgonine in hair samples by GC--MS.

The present paper describes a qualitative and quantitative method for the simultaneous detection of opiates, cocaine and benzoylecgonine from human hair samples. Every step of the analytical procedure was studied to find the optimized conditions. Nine different incubation systems were examined. The influence of different pH values of samples on the isolation of analytes from the incubation media by Bond Elut cartridges and the stability of the compounds of interest in the different incubation media and conditions were investigated. The extracting power of different incubation media was studied as well. The phosphate buffer 0.1 N at pH 5 was chosen as the extraction medium in an optimized procedure for simultaneous determination of opiates, cocaine and benzoylecgonine in hair samples. The method developed was validated. Recoveries were 90% for morphine (M), 81% for 6-monoacetylmorphine (6-AM), 90% for codeine (CD), 86% for cocaine (C) and 90% for benzoylecgonine (BE). Relative standard deviation for inter-day precision was better than 12%. The limits of detection resulted as 0.05 ng/mg for M and C, as 0.08 for 6-AM and as 0.2 ng/mg for BE. Forty hair samples collected from drug abusers admitted to centers for detoxification treatment were analyzed obtaining 23 positive results for opiates and/or cocaine. Twelve hair specimens longer than 10 cm were analyzed following a sectional approach. In the six positive cases, it was interesting to find that the 6-AM/M ratio generally decreased for each sample from the proximal segment to the distal segments. Moreover, the 6-AM/M ratio was generally lower than 1 in the intermediate and distal segments.

Adolescent↗
PubMed2005

HPLC-DAD determination of opioids, cocaine and their metabolites in plasma.

High performance liquid chromatography with diode array detection (HPLC-DAD) was used to develop a method for the simultaneous determination of morphine, codeine, 6-acetylmorphine (6AM), cocaine, benzoylecgonine (BEG), cocaethylene, methadone and its metabolite, 2-ethylidene-1,5-dimethyldiphenylpyrrolidine (EDDP), in plasma. Following solid-phase extraction with Bond Elut Certify cartridges, chromatography was performed on an X-Terra RP8 column (250 mm x 4.6 mm i.d., 5 microm particle size), using acetonitrile-phosphate buffer pH 6.53 as mobile phase and elution in the gradient mode. The detector response was linear at concentrations over the range 0.1-10 microg/mL in plasma, and the correlation coefficients for the eight drugs studied were all higher than 0.99. The average extraction recoveries from plasma ranged from 60% for BEG to 95% for methadone. The precision was acceptable, with coefficients of variation oscillating between 2.55% and 6.45%. The accuracy was found to be within satisfactory limits (+/- 8.1%). Finally, the method was applied to 21 plasma samples from fatal overdoses, obtaining positive results for two or more drugs.

Analgesics, Opioid↗
PubMed2005

The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry.

For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

Administration, Inhalation↗
PubMed2005

Are one or two dangerous? Opioid exposure in toddlers.

Ingestions of opioid analgesics by children may lead to significant toxicity as a result of depression of the respiratory and central nervous systems. A review of the medical literature was performed to determine whether low doses of opioids are dangerous in the pediatric population under 6 years old. Methadone was found to be the most toxic of the opioids; doses as low as a single tablet can lead to death. All children who have ingested any amount of methadone need to be observed in an Emergency Department (ED) for at least 6 h and considered for hospital admission. Most other opioids are better tolerated in ingestions as small as one or two tablets. Based on the limited data available for these opioids, we conclude that equianalgesic doses of 5 mg/kg of codeine or greater require 4 to 6 h of observation in the ED. Data for propoxyphene and all extended-release preparations are limited; their prolonged half-lives would suggest the need for longer observation periods. All opioid ingestions leading to respiratory depression or significant central nervous system depression require admission to an intensive care unit.

Analgesics, Opioid↗
PubMed2006

Determination of opiate alkaloids in process liquors using capillary electrophoresis.

This paper describes the determination of opiate alkaloids (morphine, codeine, oripavine and thebaine) in industrial process liquors using capillary zone electrophoresis with UV-absorption detection at 214 nm. A study of cyclodextrin type and concentration revealed that the addition of 30 mM hydroxypropyl-beta-cyclodextrin to the electrolyte solution (100mM Tris adjusted to pH 2.8) was suitable to resolve the four analytes of interest. Typical analysis time was 12 min and the limit of detection for each alkaloid was 2.5 x 10(-6) M. The results for the proposed methodology were in good agreement with those of a conventional HPLC procedure. Under the same conditions, short-end injection was used to reduce the effective separation length from 41.5 to 8.5 cm, which allowed the determination of morphine and thebaine in process liquors within 2.5 min.

Alkaloids↗
PubMed2005

Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children.

As part of a randomized clinical trial that compared three different analgesic dosing regimens ( Sutters et al., 2004 ), the purpose of this study, in children who underwent tonsillectomy, was to determine whether around-the-clock (ATC) dosing of acetaminophen with codeine, compared with as-needed (PRN) dosing, increased the frequency of moderate-to-severe opioid-related side effects (i.e., daytime sedation, lightheadedness, nightmares, nausea, vomiting, and constipation) in the first 3 days after surgery. Because no differences were found in pain intensity scores and in the amount of analgesic administered between the two ATC groups (i.e., with and without coaching), for these analyses, the two groups were combined ( n = 52) and compared with the PRN group ( n = 28). Each side effect was recoded into a dichotomous response (i.e., 0 = did not have symptoms or had slight symptoms; 1 = symptoms that were moderate, severe, or very severe) to provide an adequate sample size in each cell for the statistical analyses. No differences were found in the frequency of moderate-to-severe side effects between the ATC and PRN groups at any of the postoperative assessments. The number of children who reported moderate-to-severe daytime sedation decreased over time in both the PRN ( p = .02) and ATC groups ( p = .01). Children in the ATC groups reported a statistically significant decrease over time in vomiting ( p = .001) and feeling lightheaded or dizzy ( p = .003), and a significant increase in constipation ( p = .018). Except for daytime sedation, changes, over time, in the frequency of moderate-to-severe side effects were not observed in the PRN group.

Acetaminophen↗
PubMedDate not supplied

Decreased postpartum use of oral pain medication after a single dose of epidural morphine.

BACKGROUND: Pain after vaginal delivery may result from episiotomy, perineal laceration, or uterine involution. Many women have indwelling epidural catheters in place at delivery. We hypothesized that a small dose of epidural morphine would be an effective strategy for postpartum analgesia. METHODS: Eighty-one healthy parturients receiving epidural analgesia for labor were enrolled. Patients were randomized in double-blind fashion to 1 of 3 groups: all groups received a 4-mL volume of epidural solution consisting of saline (group 1, control), 1 mg (group 2), or 2 mg morphine (group 3) after vaginal delivery. During the first 24 hours postpartum, patients were evaluated for the amount of oral pain medication requested; visual analog scale scores for pain at rest and with movement; satisfaction with postpartum pain treatment; and opioid side effects including nausea, pruritus, urinary retention, and respiratory depression. RESULTS: Patients who received 2 mg of epidural morphine used an average of 0.7 (0-1, interquartile range) opioid-containing pain pills (acetaminophen with codeine or oxycodone) compared with 1.2 (0-2) in the 1-mg group and 1.9 (0-3) in the control group ( P = .07). There was a statistically significant difference in oral drug usage between those who received epidural morphine and those who did not ( P < .03). There were no differences in side effects except that at 12 hours postpartum there was an increase in Foley catheterization in the 1-mg morphine group ( P = .007). CONCLUSIONS: These results suggest that epidural morphine decreases the need for oral pain medication in the first 24 hours postpartum. No significant dose-dependent side effects were found.

Adolescent↗
PubMed1984

Five studies on ibuprofen for postsurgical dental pain.

Ibuprofen (Motrin, Upjohn) was evaluated in five studies using the Dental Pain Model, which is representative of most acute postsurgical pain situations. Ibuprofen 400 mg was consistently more effective than aspirin 650 mg, acetaminophen 600 mg, and both aspirin and acetaminophen when combined with codeine 60 mg. In two studies, ibuprofen 400 mg was at least as effective as zomepirac sodium 100 mg. No serious or prolonged side effects were reported in any of these studies.

Acetaminophen↗
PubMed1984

Ibuprofen in the treatment of postoperative pain.

The site and type of operation and the age of the patient help determine the intensity of postoperative pain and the level of medication necessary for relief. Controlled clinical trials have shown that ibuprofen (Motrin) is an effective and safe analgesic for patients with mild to moderate postoperative pain. In a study of 120 patients with postoperative orthopedic pain, ibuprofen was more effective than acetaminophen-codeine and had a longer duration of action.

Acetaminophen↗
PubMed1984

Combination analgesics.

Six rationales for using combination analgesics are identified, but most combinations are formulated with two rationales in mind: enhancement of analgesia and reduction of adverse effects by combining two analgesics with different mechanisms of action. Acetaminophen and aspirin are the mainstays of oral analgesic combinations. There is substantial evidence that combining an optimal dose of acetaminophen or aspirin with an oral opioid such as codeine, hydrocodone, or oxycodone produces an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equi-analgesic dose of a single constituent. The physician need not be confined to existing fixed-ratio combinations; he or she may extemporize to the patient's advantage by co-administering acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs with available oral opioids and, in select situations, co-administering oral or injectable analgesics with psychoactive drugs.

Acetaminophen↗
PubMed2000

Morphine-related metabolites differentially activate adenylyl cyclase isozymes after acute and chronic administration.

Morphine-3- and morphine-6-glucuronide are morphine's major metabolites. As morphine-6-glucuronide produces stronger analgesia than morphine, we investigated the effects of acute and chronic morphine glucuronides on adenylyl cyclase (AC) activity. Using COS-7 cells cotransfected with representatives of the nine cloned AC isozymes, we show that AC-I and V are inhibited by acute morphine and morphine-6-glucuronide, and undergo superactivation upon chronic exposure, while AC-II is stimulated by acute and inhibited by chronic treatment. Morphine-3-glucuronide had no effect. The weak opiate agonists codeine and dihydrocodeine are also addictive. These opiates, in contrast to their 3-O-demethylated metabolites morphine and dihydromorphine (formed by cytochrome P450 2D6), demonstrated neither acute inhibition nor chronic-induced superactivation. These results suggest that metabolites of morphine (morphine-6-glucuronide) and codeine/dihydrocodeine (morphine/dihydromorphine) may contribute to the development of opiate addiction.

Adenylyl Cyclase Inhibitors↗
PubMedDate not supplied

Analysis of opiates in fly larvae sampled on a putrefied cadaver.

Toxicological analyses on a putrefied cadaver are sometimes difficult to achieve, because of the absence of blood and/or urine. Drugs present in a decomposing corpse may be identified through analysis of maggots feeding off it. In this study, morphine and codeine were simultaneously identified and assayed in blood and bile of a putrefied cadaver and in the fly larvae of Calliphoridae found on the corpse.

Animals↗
PubMed1981

Determination of opiates in biological samples by glass capillary gas chromatography with electron-capture detection.

A gas chromatographic method for the simultaneous determination of morphine, 6-acetylmorphine and codeine in human plasma or blood has been developed. The samples are buffered to pH 9 and extracted on silica columns, cleaned by extraction and finally acylated with pentafluoropropionic anhydride. The derivatives formed are separated on a glass capillary column with falling glass needle injection and electron-capture detection. The choice of the extraction conditions and the preparation of suitable capillary columns are discussed.

Chromatography, Gas↗
PubMed1975

Ligand-exchange chromatography of alkaloids.

Alkaloids are separated by liquid chromatography on resins having functional carboxyl groups combined with copper (II) ions. The eluent is aqueous alcohol containing ammonia. Some resins retain alkaloids much better than others. Alkaloids studied included morphine, codeine, strychnine, atropine, papaverine, narcotine, cocaine, quinine, cinchonine and methadone.

Alkaloids↗
PubMed2000

Characteristic glucuronidation pattern of physiologic concentration of morphine in rat brain.

Formation of conjugated metabolites from morphine at a very low level in brain was studied in vitro in rats. Incubation of a low concentration of 3H-morphine with brain homogenate followed by two successive high-performance liquid chromatographic analyses showed that endogenous morphine is converted by brain enzymes to its 3- and 6-glucuronides (M-3-G and M-6-G), and codeine glucuronide (Cod-G). However, the formation of morphine-6-sulfate was likely to be low if it was produced at all. All of the cerebral hemisphere, brain stem and cerebellum were capable of producing M-3-G, M-6-G and Cod-G, although there were differences in selectivity. The capacity of the brain for glucuronide formation was far less than that of the liver, but UDP-glucuronosyltransferase in brain was much more selective in forming M-6-G and Cod-G than liver enzymes.

Animals↗
PubMed1997

Cellular inflammatory responses during immediate, developing, and established late-phase allergic cutaneous reactions: effects of cetirizine.

BACKGROUND: In some previous studies, the antihistamine cetirizine has inhibited both developing (at 6 hours) and established (at 24 hours) gross late-phase skin reactions (LPR) to pollen antigens, possibly relevant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. OBJECTIVE: To characterize cetirizine effects on gross and histologic inflammatory events from 20 minutes to 24 hours after intradermal antigen challenge in sensitive patients. METHODS: Gross and histologic responses to intradermal pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accumulated neutrophils, eosinophils, activated (EG2+) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (ECP) from eosinophils were also assessed. RESULTS: During placebo treatment, wheal-and-flare responses were significantly greater to antigen at 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antigen challenge sites than at buffer diluent sites. During cetirizine treatment, these wheal-and-flare responses to antigen were inhibited significantly (p < 0.01) but gross LPRs were not affected. During placebo treatment, significantly more cells per high-power field were found in antigen sites than in buffer sites of neutrophils at 20 minutes (p < 0.01) and 24 hours; than in eosinophils at 20 minutes, 6 hours, and 24 hours (p < 0.01 for each); than in EG2+ cells at 20 minutes (p = 0.004), 6 hours (p = 0.001), and 24 hours (p = 0.02); and at T lymphocyte sites at 24 hours (p = 0.001). Extracellular deposition of lactoferrin and ECP was significantly greater at antigen sites than at buffer sites at 6 and 24 hours. Cetirizine treatment had no significant effect on these responses. CONCLUSION: Neutrophils, eosinophils, and T lymphocytes were persistently more common at antigen sites than at buffer sites through 24 hours. Many of these neutrophils and eosinophils were activated, releasing more lactoferrin and ECP into the extracellular dermis for at least 24 hours after antigen challenge. Cetirizine inhibited gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.

Administration, Cutaneous↗
PubMed1994

Effectiveness of various medications on postoperative pain following root canal obturation.

This prospective study compared the effectiveness of nine medications and a placebo in controlling pain following obturation. A total of 588 patients who required root canal obturation were included. After obturation of root canals, each patient took one of the medications, salicylic acid (2 x 250 mg), acetaminophen (2 x 250 mg), ibuprofen (2 x 250 mg), ketoprofen (2 x 250 mg), acetaminophen (2 x 250 mg) plus codeine (2 x 250 mg), penicillin (2 x 250 mg), erythromycin base (2 x 250 mg), penicillin plus ibuprofen (2 x 250 mg), methylprednisolone (2 x 250 mg) plus penicillin (2 x 250 mg), or a placebo, every 6 h for 72 h. All medications were encapsulated in identical capsules. The patients registered their degree of discomfort on a visual analogue scale of 0 to 9. Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping (5.83% versus 21.76%). In addition, there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation.

Acetaminophen↗

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