Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. (1/68)

BACKGROUND: Day-case surgery is of great value to patients and the health service. It enables many more patients to be treated properly, and faster than before. Newer, less invasive, operative techniques will allow many more procedures to be carried out. There are many elements to successful day-case surgery. Two key components are the effectiveness of the control of pain after the operation, and the effectiveness of measures to minimise postoperative nausea and vomiting. OBJECTIVES: To enable those caring for patients undergoing day-case surgery to make the best choices for their patients and the health service, this review sought the highest quality evidence on: (1) the effectiveness of the control of pain after an operation; (2) the effectiveness of measures to minimise postoperative nausea and vomiting. METHODS: Full details of the search strategy are presented in the report. RESULTS - ANALGESIA: The systematic reviews of the literature explored whether different interventions work and, if they do work, how well they work. A number of conclusions can be drawn. RESULTS-ANALGESIA, INEFFECTIVE INTERVENTIONS: There is good evidence that some interventions are ineffective. They include: (1) transcutaneous electrical nerve stimulation in acute postoperative pain; (2) the use of local injections of opioids at sites other than the knee joint; (3) the use of dihydrocodeine, 30 mg, in acute postoperative pain (it is no better than placebo). RESULTS-ANALGESIA, INTERVENTIONS OF DOUBTFUL VALUE: Some interventions may be effective but the size of the effect or the complication of undertaking them confers no measurable benefit over conventional methods. Such interventions include: (1) injecting morphine into the knee joint after surgery: there is a small analgesic benefit which may last for up to 24 hours but there is no clear evidence that the size of the benefit is of any clinical value; (2) manoeuvres to try and anticipate pain by using pre-emptive analgesia; these are no more effective than standard methods; (3) administering non-steroidal anti-inflammatory drugs (NSAIDs) by injection or per rectum in patients who can swallow; this appears to be no more effective than giving NSAIDs by mouth and, indeed, may do more harm than good; (4) administering codeine in single doses; this has poor analgesic efficacy. RESULTS-ANALGESIA, INTERVENTIONS OF PROVEN VALUE: These include a number of oral analgesics including (at standard doses): (1) dextropropoxyphene; (2) tramadol; (3) paracetamol; (4) ibuprofen; (5) diclofenac. Diclofenac and ibuprofen at standard doses give analgesia equivalent to that obtained with 10 mg of intramuscular morphine. Each will provide at least 50% pain relief from a single oral dose in patients with moderate or severe postoperative pain. Paracetamol and codeine combinations also appear to be highly effective, although there is little information on the standard doses used in the UK. The relative effectiveness of these analgesics is compared in an effectiveness 'ladder' which can inform prescribers making choices for individual patients, or planning day-case surgery. Dose-response relationships show that higher doses of ibuprofen may be particularly effective. Topical NSAIDs (applied to the skin) are effective in minor injuries and chronic pain but there is no obvious role for them in day-case surgery. RESULTS-POSTOPERATIVE NAUSEA AND VOMITING: The proportion of patients who may feel nauseated or vomit after surgery is very variable, despite similar operations and anaesthetic techniques. Systematic review can still lead to clear estimations of effectiveness of interventions. Whichever anti-emetic is used, the choice is often between prophylactic use (trying to prevent anyone vomiting) and treating those people who do feel nauseated or who may vomit. Systematic reviews of a number of different anti-emetics show clearly that none of the anti-emetics is sufficiently effective to be used for prophylaxis. (ABSTRACT TRUNCATE  (+info)

Prevalence of drugs used in cases of alleged sexual assault. (2/68)

In recent years, there has been an increase in the number of reports in the U.S. of the use of drugs, often in conjunction with alcohol, to commit sexual assault. A study was undertaken to assess the prevalence of drug use in sexual assault cases in which substances are suspected of being involved. Law enforcement agencies, emergency rooms, and rape crisis centers across the U.S. were offered the opportunity to submit urine samples collected from victims of alleged sexual assault, where drug use was suspected, for analysis of alcohol and drugs which may be associated with sexual assault. Each sample was tested by immunoassay for amphetamines, barbiturates, benzodiazepines, cocaine metabolite (benzoylecgonine), cannabinoids, methaqualone, opiates, phencyclidine and propoxyphene. The positive screen results were confirmed by gas chromatography-mass spectroscopy (GC-MS). In addition, each sample was tested for flunitrazepam metabolites and gamma-hydroxybutyrate (GHB) by GC-MS and for ethanol by gas chromatography-flame ionization detection (GC-FID). Over a 26-month period, 1179 samples were collected and analyzed from 49 states, Puerto Rico, and the District of Columbia. The states sending the most samples were California (183), Texas (119), Florida (61), Pennsylvania (61), New York (61), Minnesota (50), Illinois (47), Indiana (44), Michigan (40), Maryland (37), Virginia (32), and Massachusetts (31). Four-hundred sixty eight of the samples were found negative for all the substances tested; 451 were positive for ethanol, 218 for cannabinoids, 97 for benzoylecgonine, 97 for benzodiazepines, 51 for amphetamines, 48 for GHB, 25 for opiates, 17 for propoxyphene, and 12 for barbiturates. There were no samples identified as positive for phencyclidine or methaqualone. In addition, 35% of the drug-positive samples contained multiple drugs. This study indicates that, with respect to alleged sexual assault cases, the prevalence of ethanol is very high, followed by cannabinoids, cocaine, benzodiazepines, amphetamines, and GHB. Although only a couple of substances have been implicated with sexual assault, this study has shown that almost 20 different substances have been associated with this crime. This study also raises the concern of illicit and licit drug use in sexual assault cases and suggests the need to test for a range of drugs in these cases. It also highlights the need to test for GHB, which is not generally tested for in a normal toxicology screen.  (+info)

Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1. (3/68)

Human liver carboxylesterases catalyze the hydrolysis of apolar drug or xenobiotic esters into more soluble acid and alcohol products for elimination. Two carboxylesterases, hCE-1 and hCE-2, have been purified and characterized with respect to their role in cocaine and heroin hydrolysis. The binding of meperidine (Demerol) and propoxyphene (Darvon) was examined in a competitive binding, spectrophotometric assay. The hCE-1 and hCE-2 bound both drugs, with Ki values in the 0.4- to 1.3-mM range. Meperidine was hydrolyzed to meperidinic acid and ethanol by hCE-1 but not hCE-2. The Km of hCE-1 for meperidine was 1.9 mM and the kcat (catalytic rate constant) was 0.67 min-1. Hydrolysis of meperidine by hCE-1 was consistent with its specificity for hydrolysis of esters containing simple aliphatic alcohol substituents. Hence, hCE-1 in human liver microsomes may play an important role in meperidine elimination. Propoxyphene was not hydrolyzed by hCE-1 or hCE-2. This observation is consistent with the absence of a major hydrolytic pathway for propoxyphene metabolism in humans.  (+info)

Hypersensitivity pneumonitis associated with co-proxamol (paracetamol + dextropropoxyphene) therapy. (4/68)

A 61-year-old man developed hypersensitivity pneumonitis and skin rash in close association with taking co-proxamol. These problems occurred in spite of being treated with prednisolone 40 mg daily (20 mg daily at the time of presentation) for assumed cranial arteritis. A therapeutic challenge with paracetamol was negative and the patient continues to take this drug. It seems likely that this patient's rash and hypersensitivity pneumonitis was caused by dextropropoxyphene. Dextropropoxyphene has not been reported previously as a cause of hypersensitivity pneumonitis.  (+info)

Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents. (5/68)

OBJECTIVE: Norpropoxyphene (NP) is a major metabolite of propoxyphene (P), a relatively weak mu-opioid receptor agonist. Toxic blood concentrations ranging from 3 to 180 mumol/l have been reported and the accumulation of NP in cardiac tissue leads to naloxone-insensitive cardiotoxicity. Since several lines of evidence suggest that not only block of INa but also IK block may contribute to the non-opioid cardiotoxic effects of P and NP, we investigated the effects of P and NP on HERG channels. HERG presumably encodes IKr, the rapidly-activating delayed rectifier K+ current, which is known to have an important role in initiating repolarization of action potentials in cardiac myocytes. METHODS: Using the 2-microelectrode voltage clamp technique we investigated the interaction of P and NP with HERG channels, expressed in Xenopus oocytes. RESULTS: Our experiments show that low drug concentrations (5 mumol/l) facilitate HERG currents, while higher drug concentrations block HERG currents (IC50-values of approx. 40 mumol/l) and dramatically shift the reversal potential to a more positive value because of a 30-fold increased Na(+)-permeability. P and NP also alter gating of HERG channels by slowing down channel activation and accelerating channel deactivation kinetics. The mutant S631C nullifies the effect of P and NP on the channel's K(+)-selectivity. CONCLUSION: P and NP show a complex and unique drug-channel interaction, which includes altering ion-selectivity and gating. Site-directed mutagenesis suggests that an interaction with S631 contributes to the drug-induced disruption of K(+)-selectivity. No specific role of the minK subunit in the HERG block mechanism could be determined.  (+info)

An unusual multiple drug intoxication case involving citalopram. (6/68)

A 47-year-old male with a history of drug abuse and suicide attempts was found dead at home. The death scene investigation showed evidence of cocaine abuse and multiple drug ingestion. Citralopram, a new selective serotonin reuptake inhibitor, cocaine, oxycodone, promethazine, propoxyphene, and norpropoxyphene were identified and quantitated in the postmortem samples by gas chromatography-mass spectrometry. The concentration of citalopram in the femoral blood was 0.88 mg/L. The heart blood concentration was 1.16 mg/L. Femoral blood concentrations of the other drugs were as follows: cocaine, 0.03 mg/L; oxycodone, 0.06 mg/L; promethazine, 0.02 mg/L; propoxyphene, 0.02 mg/L; and norpropoxyphene, 0.07 mg/L. Other tissue samples were also analyzed. The concentrations of cocaine, oxycodone, promethazine, and propoxyphene in the blood, liver, brain, and gastric contents did not suggest an intentional overdose. However, the possibility of multiple drug interactions including citalopram was evident. In this case, the citalopram concentrations were consistent with those reported in fatal cases involving multiple drug use. Citalopram was present in urine at a concentration of 0.9 mg/L.  (+info)

Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel. (7/68)

OBJECTIVE: As compared with voltage-gated K(+) channels (Kv-type), our knowledge of the structure-function and pharmacology of two-pore background K(+) channels is still very limited. Here we have used a drug- and mutagenesis-based approach to study the effect of the antidepressant fluoxetine (FL) and analgesic D-norpropoxyphene (NORP) on the cardiac two-pore background K(+) channel. METHODS: Whole-cell currents of the cTBAK-1 channel expressed in Xenopus laevis oocytes were investigated using conventional two-microelectrode voltage-clamp recording method combined with functional mutagenesis of the channel protein. RESULTS: Both drugs inhibit cTBAK-1 current: FL proved to be a voltage-dependent pore-blocker, while NORP induced a change in the selectivity of cTBAK-1 giving rise to a shift in the reversal potential (E(rev)) toward more positive voltages due to an increased Na(+) permeability. Mutations were introduced into the selectivity filter of the first (Y105F) and the second (F211Y) pore to mimic the P-region of HERG (GFGN) and Kv1.1 (GYGD) channels. Point mutations in the channel resulted in two distinct phenotypes of cTBAK-1: the mutant Y105F channel lost its selectivity and was unaffected by NORP, in contrast to the F211Y mutant. CONCLUSION: FL and NORP block the current of cTBAK-1 channels differently, the latter modified the selectivity of the channel pore. Our mutagenesis study revealed that NORP interacts with the selectivity filter of cTBAK-1. The significant role of the GYGD motif in this type of K(+) channels is emphasized.  (+info)

Co-proxamol and suicide: a study of national mortality statistics and local non-fatal self poisonings. (8/68)

OBJECTIVES: To examine the incidence of suicides due to co-proxamol compared with tricyclic antidepressants and paracetamol, and to compare fatality rates for self poisonings with these drugs. DESIGN: Analysis of routinely collected national and local data on suicides and self poisonings. SETTING: Records of suicides in England and Wales 1997-9; non-fatal self poisonings in Oxford District 1997-9. DATA SOURCES: Office for National Statistics and Oxford monitoring system for attempted suicide. MAIN OUTCOME MEASURES: Incidence of suicides with co-proxamol or tricyclic antidepressants or paracetamol. Ratios of fatal to non-fatal self poisonings. RESULTS: Co-proxamol alone accounted for 5% of all suicides. Of 4162 drug related suicides, 18% (766) involved co-proxamol alone, 22% (927) tricyclic antidepressants alone, and 9% (368) paracetamol alone. A higher proportion of suicides in the 10-24 year age group were due to co-proxamol than in the other age groups. The odds of dying after overdose with co-proxamol was 2.3 times (95% confidence interval 2.1 to 2.5) that for tricyclic antidepressants and 28.1 times (24.9 to 32.9) that for paracetamol. CONCLUSIONS: Self poisoning with co-proxamol is particularly dangerous and contributes substantially to drug related suicides. Restricting availability of co-proxamol could have an important role in suicide prevention.  (+info)

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