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PubMed1980

Methodological considerations in the evaluation of analgesic combinations: acetaminophen (paracetamol) and hydrocodone in postpartum pain.

1 In a double-blind study, 108 postpartum patients received single oral doses of either placebo, acetaminophen (paracetamol) 1000 mg, hydrocodone 10 mg, the combination of acetaminophen plus hydrocodone, or codeine 60 mg. 2 In the 2X2 factorial analysis, both the acetaminophen and hydrocodone effects were statistically significant, whereas the interaction contrast was not. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the assumption that these constituents are producing analgesia by different mechanisms. 3 Although significantly superior to placebo, codeine seemed to be inferior to the other treatments. 4 Compared with placebo, both codeine and hydrocodone (centrally acting narcotics) seemed relatively more effective in uterine cramp than episiotomy pain; the reverse seemed true with acetaminophen (a peripherally acting analgesic). 5 Some methodological implications for the evaluation of analgesic combinations are discussed.

Acetaminophen↗
PubMed1976

General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.

1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.

Administration, Oral↗
PubMed1993

Opiate concentrations in human head, axillary, and pubic hair.

The concentrations of morphine and codeine were investigated in hair from the head, axillary and pubic regions obtained from 12 fatal heroin cases. Hair preparation involves a decontamination procedure in dichloromethane at 37 degrees C for 15 min, solubilization in sodium hydroxyde at 100 degrees C for 5 min, neutralization with hydrochloric acid and centrifugation. After extraction in chloroform-isopropanol-n-heptane (50:17:33; v/v) at pH 9.2, drugs were derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column. Quantification was done by GC/MS using selected ion monitoring. The highest morphine concentrations were found in pubic hair (0.80 to 41.34 ng/mg), followed by hair of the head (0.62 to 27.10 ng/mg), and axillary hair (0.40 to 24.20 ng/mg). Codeine was also detected in all samples, and the codeine-to-morphine ratios ranged from 0.069 to 0.273. The differences observed in drug concentration in the 3 types of hair are discussed in the light of the existing literature.

Adult↗
PubMed1997

The efficacy of nonopioid analgesics for postoperative dental pain: a meta-analysis.

The evidence for the efficacy of nonopioid analgesics in the dental pain model was examined by conducting a meta-analysis. Studies were obtained by searching the literature from August 1996 back to 1975 using the terms pain, analgesics, and dentistry. This led to the review of 294 articles, of which 33 studies met the inclusion criteria. Pain scale results were transformed into a common percent scale and converted to N-weighted means with differences in efficacy considered significant using a 95% confidence interval. Collectively, therapeutic doses of the nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in dentistry were significantly more efficacious than the combination of acetaminophen (600 or 650 mg) with codeine (60 mg). Similarly, specific doses of each of diflunisal, flurbiprofen, ibuprofen, and ketorolac were significantly more efficacious than the commonly used acetaminophen-codeine combination. These quantitative results show that particular NSAIDs may be more efficacious than the acetaminophen-codeine combination for relief of postoperative dental pain.

Acetaminophen↗
PubMed1988

Ketoprofen in oral surgery pain: a review.

Ketoprofen is a new peripherally acting analgesic and the most recently introduced nonsteroidal anti-inflammatory drug in the United States with indication for management of nonarthritic pain. Three 6-hour double-blind, single-dose, placebo-controlled studies in which patients who had undergone dental impaction surgery took ketoprofen or a comparator drug are reviewed. In the first study, ketoprofen 25, 50, and 100 mg was compared with aspirin 650 mg and placebo in 153 patients. In comparison with aspirin, significant (P less than 0.001) differences favoring ketoprofen at each dose level were found for all measures of analgesic efficacy. For the combined ketoprofen groups, 60% of the patients rated treatment as very good or excellent, compared with 16% in the aspirin group. The second study compared ketoprofen 25, 50, and 100 mg with codeine 90 mg and placebo in 129 patients. Ketoprofen appeared to have a more rapid onset, higher peak effect, and longer duration of pain relief than codeine. At least 70% of patients in each of the ketoprofen groups rated the test medication as very good or excellent, compared with only 7% of the patients in the codeine group. The third study compared ketoprofen 25 and 100 mg with ibuprofen 400 mg and placebo in 161 patients. Ketoprofen 100 mg had a faster onset of effect, the highest peak effect, and the longest duration of action over the 6-hour evaluation. Ketoprofen treatment was not associated with any unusual or serious side effects in any of the three studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1998

Electrostimulation of catecholamine release in the eel: modulation by antagonists and autocrine agonists.

The innervated chromaffin cells of the eel (Anguilla rostrata) release norepinephrine (NE) and epinephrine (E), while a component of the macrovascular wall releases dopamine (DA). The release of the three catecholamines is governed by complex controls which include adrenergic, nicotinergic, muscarinergic, and opioid mechanisms. To gain insight into the interactions between neural and autocrine factors in stimulated catecholamine release, we investigated the effect of adrenergic (phentolamine and propranolol) and muscarinergic (atropine) receptor antagonists, and of autocrine opioids (met-enkephalin, codeine, and morphine) on electrostimulated catecholamine secretion in situ. The hind brain (close to the root of nerve IX) of anesthetized eels was stimulated at four different time points, and segments of the posterior cardinal vein or the caudal vein were perfused with a saline solution, with or without test substances. Electrostimulation (30 s) four times within a total study duration of 14 min increased the release of DA, NE, and E into the perfusate of the cardinal vein. The vessel contains the innervated adrenomedullary equivalent. In the noninnervated caudal vein electrical stimulation had no impact on total DA release, while there was a slight decrease of NE release and a slight increase of E release. In the cardinal vein, both the alpha-adrenergic receptor antagonist phentolamine and the beta-adrenergic receptor antagonist propranolol strongly reduced the effect of electrostimulation on catecholamine release. Met-enkephalin reduced the release of all three catecholamines to a similar degree; its impact on NE release was especially strong. Codeine reduced the catecholamine release moderately, while morphine had no effect. Atropine reduced the release of all three catecholamines in a pattern similar to that of met-enkephalin. The findings on the posterior cardinal vein indicate that neurally stimulated NE and E release (1) involves autocrine/paracrine adrenergic mechanisms, (2) involves a muscarinergic mechanism, and possibly also endogenous codeine and morphine; and (3) is antagonized by met-enkephalin. The findings on the caudal vein are further evidence that macrovascular DA release is not under direct neural control.

Adrenergic Agonists↗
PubMed2006

Unique cytochromes P450 in human brain: implication in disease pathogenesis.

Cytochromes P450 is a family of heme proteins that metabolize xenobiotics including drugs. Unique human brain cytochrome P450 enzymes metabolize xenobiotics including drugs to active/inactive metabolites through biotransformation pathways that are different from the well-characterized ones in liver. We have identified an alternate spliced functional transcript of CYP2D7 containing partial inclusion of intron 6 in human brain but not in liver or kidney from the same individual. Genotyping revealed the presence of the frame-shift mutation 138delT only in those subjects who expressed the brain variant CYP2D7, which metabolizes codeine exclusively to morphine unlike hepatic CYP2D6 that metabolizes codeine to nor codeine and morphine. CYP1A1 bioactivates polycyclic aromatic hydrocarbons to reactive DNA binding metabolites and initiates carcinogenesis. We have identified a unique splice variant of CYP1A1 having deletion of 87 bp of exon 6 which is present in human brain but not in liver of the same individual. We present evidence for the existence of biotransformation pathways in human brain that are dissimilar from known pathways in liver. Identification and characterization of novel CNS-specific P450 enzymes generated by alternate splicing of known genes or as yet unidentified genes may help predict consequences of exposure to xenobiotics including pesticides in the brain.

Alternative Splicing↗
PubMed1999

The effect of salmeterol and salbutamol on mediator release and skin responses in immediate and late phase allergic cutaneous reactions.

BACKGROUND: Salmeterol is a long-acting beta2-agonist which in animal studies has been shown to possess anti-inflammatory effects on early (EAR) and late (LPR) phase allergic responses. PURPOSE: To evaluate the anti-inflammatory effects of intradermally injected salmeterol and salbutamol on clinical and biochemical EAR and LPR in human skin. METHODS: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and prostaglandin D2 (PGD2) release by microdialysis technique in EAR, and measurement of mediators in LPR by suction blister technique. RESULTS: Both beta2-agonists inhibited allergen-induced histamine release and wheal and flare reactions with maximum inhibition of 40-50% at 10(-6) M, a concentration which reduced PGD2 synthesis by approximately 55%. Histamine release by codeine and skin reactions to codeine and histamine were not or only marginally reduced. Salmeterol and salbutamol (10(-6) M) inhibited clinical LPR at 6 h by 71% and 48%, Except for the clinical LPR, no statistical differences were found between the two drugs on any parameters. None of the drugs inhibited levels of histamine, tryptase, myeloperoxidase, or eosinophil cationic protein in LPR. CONCLUSIONS: Salmeterol and salbutamol inhibited allergen-induced skin responses, and reduced mediator release in EAR but not LPR. In general, the anti-inflammatory effects of salmeterol did not differ from those induced by salbutamol.

Adrenergic beta-Agonists↗
PubMed2005

Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.

A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of opiates (6-monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 degrees C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5-570.0 ng/g for 6-monoacetylmorphine, 8.7-154.8 ng/g for morphine and 7.9-127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

Calibration↗
PubMed2004

The social ecology of changing pain management: do I have to cry?

OBJECTIVE: To improve acute pain management for children with systematic assessment and appropriate analgesia. DESIGN: An action research design was used; pre-post data were collected during a four-phase intervention. The intervention was a social ecological approach to changing pain assessment and prescription practices. SETTING: A university-affiliated public hospital in the greater Los Angeles area. PARTICIPANTS: An interdisciplinary team of clinicians and hospital administrators were engaged in implementing new pain management procedures for children with postoperative and procedural pain. INTERVENTIONS: We implemented the Poker Chip Tool as a standard pain assessment tool, changed policy to make morphine drug of choice for acute postoperative pain, provided extensive educational activities, and conducted weekly rounds with anesthesiologist/intensivist, nurses, pharmacist, and child life specialist. Role modeling by leaders was used to build skill in interdisciplinary collaboration for staff. We promoted the initiative as an activity of the medical center strategic plan. Efforts were linked to national shifts in pain management through guideline review and use of a visiting expert. OUTCOME MEASURES: Charts were audited for assessment of pain intensity. Doses dispensed by pharmacy were used as a proxy measure of analgesia administered to children to establish change in pattern of analgesic use. RESULTS: In Phase I: 54% of charts audited had documentation of pain intensity. This rate climbed to Phase II, 93% of the audited charts at full implementation and stabilized at 84% at the project conclusion. Record of doses of analgesia dispensed demonstrated a shift from reliance on meperidine to morphine and acetaminophen with codeine. The relative rates demonstrated a 100% increase in acetaminophen with codeine distributed from the beginning of the study to full implementation of the project (chi(2) = 9.01, df = 1, p < 0.002). The relative rate for meperidine demonstrated a 250% decrease (chi(2) = 12.26, df = 1, p < 0.0004), and the relative rate for morphine exhibited a 455% increase (chi(2) = 209.20, df = 1, p < 0.0001). By the final phase (IV: Evaluation), meperidine was only 1% of the analgesia dispensed. Morphine doses that were initially 35% climbed to 62% at the close of the study. Acetaminophen with codeine shifted correspondingly from 24% to 36%. Anecdotal reports suggested that skills in assessment and building collaboration generalized to other patient care situations. CONCLUSIONS: Using a social ecology approach that focused simultaneously on the environment (ward, medical center, and national scene) and relationships among the clinical team improved pain management practices. These changes took place over 2 years and were sustained 2 years after the intense intervention.

Analgesia↗
PubMed2006

Current and future centrally acting antitussives.

The purpose of this review is to highlight some important issues regarding current centrally acting antitussive drugs as well as discuss the implications of these matters on the development of future cough suppressants. Drugs that act in the central nervous system to inhibit cough are termed centrally acting and this designation is based exclusively on evidence obtained from animal models. This classification can include drugs that act both at peripheral and central sites following systemic administration. These drugs are intended to reduce the frequency and/or intensity of coughing resulting from disorders of any etiology. There are a number of central cough suppressants identified by their efficacy in animal models and the most prominent of these are codeine and dextromethorphan. Although the exact neural elements on which these drugs act are currently unknown, they are thought to inhibit a functionally identified component of the central system for cough known as the gating mechanism. The efficacy of codeine and dextromethorphan in humans has recently been questioned. These drugs are less effective on cough induced by upper airway disorders than in pathological conditions involving the lower airways in humans. The reasons for this difference in antitussive sensitivity are not clear. We propose that sensory afferents from different regions of the airways actuate coughing in humans by antitussive sensitive and insensitive control elements in the central nervous system. This hypothesis is consistent with results from an animal model in which laryngeal and tracheobronchial cough had different sensitivities to codeine. Other factors that may be very important in the action of central antitussive drugs in humans include the role of sensations produced by a tussigenic stimulus as well as plasticity of central pathways in response to airway inflammation. Resolution of these issues in the human will be a challenging process, but one which will lay the foundation for the development of more effective cough suppressants.

Animals↗
PubMed2001

Capillary electrophoresis-electrospray ionization ion trap mass spectrometry for analysis and confirmation testing of morphine and related compounds in urine.

Using an aqueous background electrolyte containing 25 mM ammonium acetate and NH3 (pH 9), CE-tandem MS and CE-triple MS with atmospheric pressure electrospray ionization in the positive ion mode are shown to represent attractive approaches for analysis and confirmation testing of morphine (MOR) and related opioids in human urine. Injection of plain or diluted urine permits monitoring of solutes at concentrations above 2-5 microg/ml. For the recognition of lower concentrations, solute extraction and concentration is required. Liquid-liquid extraction at alkaline pH is shown to be suitable for analysis of free opioids only whereas solid-phase extraction using a mixed-mode polymer phase is demonstrated to permit analysis of both free and glucuronidated opioids. The former sample preparation approach, however, requires about half of the time only. Commencing with 2 ml of urine, reconstitution to provide a sample volume of 0.2 ml and hydrodynamic sample injection, detection limits for free opioids are shown to be on the 100-200 ng/ml drug level. Much improved (ppb) sensitivity is obtained by infusing the extract directly into the source of the MS system. However, solutes that produce equal fragments (such as the two glucuronides of MOR) can thereby not be distinguished. CE-tandem MS and CE-triple MS are demonstrated to be suitable to confirm the presence of MOR, MOR-3-glucuronide, 6-monoacetylmorphine, codeine, codeine-6-glucuronide, dihydrocodeine, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in a toxicological quality control urine. The same is shown for selected metabolites of codeine and dihydrocodeine in urines collected after administration of pharmaceutical preparations.

Electrophoresis, Capillary↗
PubMed1996

Combination analgesic involvement in the pathogenesis of analgesic nephropathy: the European perspective.

Analgesic nephropathy (AN) is a chronic renal disease characterized by renal papillary necrosis and interstitial nephritis caused by excessive consumption of analgesic mixtures. In a recent study, diagnostic criteria for AN, based on a computed tomography scan investigation without contrast, were presented. The observation of a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications was found to have a high diagnostic performance. Although several case control studies and two prospective studies demonstrated the association between analgesic abuse and nephropathy, the nephrotoxicity of the different analgesic products had not been clearly established. Analgesic abuse can be defined as a daily consumption of analgesic mixtures over a several-year period. Abuse of single analgesics is rare; it has been clearly demonstrated that abusers prefer analgesic mixtures. In Belgium, the prevalence of AN was positively related to the sales of analgesic mixtures containing two analgesic components plus caffeine and/or codeine. This relationship could not be observed for analgesics containing only one analgesic component plus caffeine and/or codeine. Moreover, during a European multicenter study, nephrotoxicity of different combinations of analgesic mixtures (all containing caffeine and/or codeine) could be documented in the absence of any previous phenacetin consumption. Epidemiologic observations in Sweden, France, and Belgium regarding incidence of AN, sales figures of analgesics, and legislative measurements concerning analgesic consumption supported the previous observations.

Analgesics↗
PubMed1982

Detection and measurement of opium alkaloids and metabolites in urine of opium eaters by methane chemical ionization mass fragmentography.

A gas chromatographic-mass spectrometric assay for eight opium alkaloids in human urine following opium ingestion is described. The compounds were extracted from urine with methylene chloride-isopropanol (7:3, v/v) at pH 9.5, evaporated, derivatized with Tri-Sil Z and analyzed by methane chemical ionization mass fragmentography. The method in sensitive to ca. 0.01 microgram/ml for morphine and codeine and ca. 0.05 microgram/ml for the other compounds. Adsorption problems on the gas chromatography column prevented obtaining reproducible results for the measurement of noscapine. Extraction efficiencies over the pH range of 8-11 for the eight compounds are reported. Retention times of the opium alkaloids were determined using five different liquid phases (3%) on Gas-Chrom Q (100-120 mesh) and two column lengths (36 cm and 183 cm). The 36-cm column packed with OV-210 was selected for use in the assay. Ions were selected for monitoring for each component from their methane chemical ionization spectrum to provide the needed sensitivity and specificity for analysis of a multi-component mixture. The assay was used for the analysis of an "opium eater's" urine. Morphine, codeine, nomorphine, norcodeine and noscapine were detected; however, no evidence was obtained for thebaine, papaverine or oripavine. Unconjugated morphine (0.64 microgram/ml) was present at nearly twice the concentration of codeine (0.37 microgram/ml) and normorphine and norcodeine were present in equal amounts (ca. 0.15 microgram/ml).

Gas Chromatography-Mass Spectrometry↗
PubMed2001

Experience with urine drug testing by the Correctional Service of Canada.

The Correctional Service of Canada implemented a urine drug-screening program over 10 years ago. The objective of this report is to describe the program and drug test results in this program for 1999. Offenders in Canadian federal correctional institutions and those living in the community on conditional release were subject to urine drug testing. Urine specimens were collected at correctional facilities and shipped by courier to MAXXAM Analytics Inc. laboratory. All urine specimens were analyzed for amphetamines, cannabinoids, cocaine metabolite (benzoylecgonine), opiates, phencyclidine, benzodiazepines, methyl phenidate, meperidine, pentazocine and fluoxetine by immunoassay screening (homogeneous EIA and ELISA assays) followed by GC-MS confirmation. Ethyl alcohol was analyzed when specifically requested. Alternative screening and confirmation methods with lower cut-off values were used, whenever urine specimens were dilute (creatinine <20mg/dl and specific gravity <or=1.003). The number of urine specimens analyzed was 44,722 in 1999 and 6.2% of these specimens were dilute based on creatinine and specific gravity analysis. The positive rate for one or more drugs was 25.5% in 1999. The highest drug positive rates were for cannabinoids (10.7%), morphine (3.2%), cocaine metabolite (3.2%), codeine (2.6%), oxazepam (2.1%), temazepam (1.1%) and ethyl alcohol (1.0%). In correctional institutions (8606 non-dilute specimens analyzed in 1999), 16.4% were positive for cannabinoids, 4.9% positive for codeine and/or morphine and 2.7% positive for oxazepam and/or temazepam. In the 537 dilute specimens collected in institutions, 21% were positive for cannabinoids, 1.3% positive for codeine and/or morphine and 1.3% positive for oxazepam and/or temazepam. In the community setting, 33,928 non-dilute specimens were collected in 1999 (9.0% were positive for cannabinoids and 3.5% positive for cocaine metabolite). In the 1651 dilute specimens collected from offenders in the community in 1999, 12.6% were positive for cannabinoids and 9.5% positive for cocaine metabolite. We conclude that forensic urine drug testing provides an objective measure of drug use by offenders in Canadian federal institutions and those offenders living in the community on conditional release.

Canada↗
PubMed2000

The high performance liquid chromatography electrospray ionization mass spectrometry analysis of diverse basic pharmaceuticals on cyanopropyl and pentafluorophenylpropyl stationary phases.

Cyanopropyl (CN) and pentafluorophenylpropyl (PFPP) modified silica columns give good retention and good peak shape for the high performance liquid chromatography/electrospray ionization/mass spectrometry (HPLC/ESI/MS) analysis of several classes of basic drugs. These phases enhance the ESI-MS signal by providing good retention of basic drugs with a mobile phase containing 90% acetonitrile. With C18 columns, in order to achieve good retention of basic drugs, only a mobile phase containing less than 40% acetonitrile can be used. Higher concentrations of acetonitrile produce a larger MS signal in the ESI process; the MS signal was a factor of 9 and 12 times greater on the CN and PFPP phases when compared with the C18 phase for the analysis of codeine. The C18 phase required only 4.0-6.0% acetonitrile to obtain the same retention time for codeine. The CN and PFPP stationary phases can be used for the analysis of a range of basic drugs, including many compounds which are poorly retained on the popular C18 and C8 stationary phases. Applications of CN and PFPP columns in the HPLC/ESI/MS of basic drugs include the analysis of antimalarials, such as quinine, bronchodilators, such as salbutamol and tulobuterol, cardioactive drugs, such as procainamide and beta-blockers, tricyclic antidepressants (TCAs), such as protriptyline and trimipramine and alkaloids, such as morphine and codeine. The CN and PFPP phases are also useful for the analysis of bufuralol and its metabolite, hydroxy-bufuralol. All the above analyses were performed using the same mobile phase, 90% acetonitrile; thus the HPLC method development process was expedited. The CN and PFPP phases also gave reproducible retention times and peak shape after more than 8 h of analyses.

Chromatography, High Pressure Liquid↗
PubMed1998

[Conventional techniques for analgesia: opioids and non-opioids. Indications, adverse effects and monitoring].

Morphine dosage must be carefully adapted in patients with renal failure or severe liver failure. The i.v. route is used for morphine titration in the post anaesthesia care unit (PACU), or for analgesia in children. Systematic (not on demand) intramuscular or subcutaneous morphine must be administered at intervals not longer than 4 hours. Dosage is best determined after i.v. titration in the PACU. Codeine, administered orally, is metabolised into morphine. Codeine has almost no effect in 7% of Caucasians and at least 15% of Asians. Nalbuphine, which has a sedative effect and a short half-life, is mainly used in children. Paracetamol (acetaminophen) is used orally or rectally, most often in combination with codeine. Paracetamol dosage is 60-90 mg.kg-1.d-1, including a 20 mg (orally), or 40 mg (rectally) loading dose. Its therapeutic ratio is low, with a potential hepatic toxicity. Dosage must be lowered in alcoholics or in patients under isoniazide therapy. Non-steroidal anti-inflammatory drugs are powerful antinociceptive agents. Their use must be restricted to the first 5 postoperative days. Their major contraindications are kidney failure, risk of gastrointestinal bleeding, coagulation disorders, allergy. They also have a marked morphine sparing effect and reduce therefore the respiratory depression induced by morphine.

Analgesics, Non-Narcotic↗
PubMed2003

Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.

A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

Calibration↗