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Navneet Kapur - One of the best experts on this subject based on the ideXlab platform.
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relative toxicity of analgesics commonly used for intentional self poisoning a study of case fatality based on fatal and non fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, Dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with Dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of Dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, Dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with Dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of Dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Suicide and open verdict deaths by all causes, and suicide, open verdict, and accidental deaths due to poisoning by all drugs, co-proxamol alone, and seven other analgesics alone (or with alcohol) in England and Wales, 1998–2010.
2012Co-Authors: Keith Hawton, Navneet Kapur, Claudia Wells, Helen Bergen, Sue Simkin, David GunnellAbstract:aOther analgesics: co-codamol, codeine, co-dydramol, Dihydrocodeine, NSAIDS, paracetamol, and tramadol.bPercentage of all drug-poisoning deaths.
Wolfgang Thormann - One of the best experts on this subject based on the ideXlab platform.
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the visceral and somatic antinociceptive effects of Dihydrocodeine and its metabolite dihydromorphine a cross over study with extensive and quinidine induced poor metabolizers
British Journal of Clinical Pharmacology, 1998Co-Authors: Clive H Wildersmith, Edith Hufschmid, Wolfgang ThormannAbstract:Aims Dihydrocodeine is metabolized to dihydromorphine via the isoenzyme cytochrome P450 2D6, whose activity is determined by genetic polymorphism. The importance of the dihydromorphine metabolites for analgesia in poor metabolizers is unclear. The aim of this study was to assess the importance of the dihydromorphine metabolites of Dihydrocodeine in analgesia by investigating the effects of Dihydrocodeine on somatic and visceral pain thresholds in extensive and quinidine-induced poor metabolizers. Methods Eleven healthy subjects participated in a double-blind, randomized, placebo-controlled, four-way cross-over study comparing the effects of single doses of placebo and slow-release Dihydrocodeine 60 mg with and without premedication with quinidine sulphate 50 mg on electrical, heat and rectal distension pain tolerance thresholds. Plasma concentrations and urinary excretion of Dihydrocodeine and dihydromorphine were measured. Results In quinidine-induced poor metabolizers the plasma concentrations of dihydromorphine were reduced between 3 and 4 fold from 1.5 h to 13.5 h after dosing (P<0.005) and urinary excretion of dihydromorphine in the first 12 h was decreased from 0.91% to 0.28% of the Dihydrocodeine dose (P<0.001). Dihydrocodeine significantly raised the heat pain tolerance thresholds (at 3.3 h and 5 h postdosing, P<0.05) and the rectal distension defaecatory urge (at 3.3 h and 10 h postdosing, P<0.02) and pain tolerance thresholds (at 3.3 h and 5 h postdosing, P<0.05) compared with placebo. Premedication with quinidine did not change the effects of Dihydrocodeine on pain thresholds, but decreased the effect of Dihydrocodeine on defaecatory urge thresholds (at 1.5 h, 3.3 h and 10 h postdosing, P<0.05). Conclusions In quinidine-induced poor metabolizers significant reduction in dihydromorphine metabolite production did not result in diminished analgesic effects of a single dose of Dihydrocodeine. The metabolism of Dihydrocodeine to dihydromorphine may therefore not be of clinical importance for analgesia. This conclusion must however, be confirmed with repeated dosing in patients with pain.
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characterization of the genetic polymorphism of Dihydrocodeine o demethylation in man via analysis of urinary Dihydrocodeine and dihydromorphine by micellar electrokinetic capillary chromatography
Journal of Chromatography B: Biomedical Sciences and Applications, 1996Co-Authors: Edith Hufschmid, Clive H Wildersmith, Regula Theurillat, Wolfgang ThormannAbstract:The genetic polymorphism of Dihydrocodeine O-demethylation in man via analysis of urinary Dihydrocodeine (DHC) and dihydromorphine (DHM) by micellar electrokinetic capillary chromatography is described. Ten healthy subjects which are known to be extensive metabolizers for debrisoquine ingested 60 mg of DHC and collected their 0-12 h urines. In these samples, about 1% of the administered DHC equivalents are shown to be excreted as DHM. Premedication of 50 mg quinidine sulfate to the same subjects is demonstrated to significantly reduce (3-4 fold) the amount of O-demethylation of DHC, a metabolic step which is thereby demonstrated to co-segregate with the hydroxylation of debrisoquine. Thus, in analogy to codeine and other substrates, extensive and poor metabolizer phenotypes for DHC can be distinguished. Using the urinary DHC/DHM metabolic ratio to characterize the extent of O-demethylation, the metabolic ratio ranges of extensive and poor metabolizers in a frequency histogram are shown to partially overlap. Thus, classification of borderline values is not unequivocal and DHC should therefore not be employed for routine pharmacogenetic screening purposes. Nevertheless, the method is valuable for metabolic research and preliminary data demonstrate that the same assay could also be used to explore the metabolism of codeine.
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exploration of the metabolism of Dihydrocodeine via determination of its metabolites in human urine using micellar electrokinetic capillary chromatography
Journal of Chromatography B: Biomedical Sciences and Applications, 1995Co-Authors: Edith Hufschmid, Regula Theurillat, Ulrich Martin, Wolfgang ThormannAbstract:After single-dose administration of 40 or 60 mg of Dihydrocodeine (DHC, in a slow-release tablet) to four healthy individuals known to be extensive metabolizers of debrisoquine, the urinary excretion of DHC and its four major metabolites, Dihydrocodeine-6-glucuronide, norDihydrocodeine, dihydromorphine and nordihydromorphine, was assessed using micellar electrokinetic capillary chromatography (MECC). DHC and two of its metabolites (Dihydrocodeine-6-glucuronide and norDihydrocodeine) could be analyzed by direct urine injection, whereas the metabolic pattern was obtained by copolymeric bonded-phase extraction of the solutes from both plain and hydrolyzed urine specimens prior to analysis. The total DHC equivalents excreted within 8 and 24 h were determined to be 30.4 +/- 7.7% (n = 5) and 63.8 +/- 6.1% (n = 2), respectively, and only about 4% of the excreted DHC equivalents were identified as morphinoids. Furthermore, almost no morphinoid metabolites of DHC could be found after administration of quinidine (200 mg of quinidine sulfate) 2 h prior to DHC intake.
Laura Sheard - One of the best experts on this subject based on the ideXlab platform.
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ral Substance Abuse Treatment, ssBioMed CentPrevention, and Policy Open AcceResearch The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS)
2016Co-Authors: Laura Sheard, Nat Mj Wright, Hany G El-sayeh, Clive E AdamsAbstract:prisons project: a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxificatio
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The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxification
Substance Abuse Treatment Prevention and Policy, 2009Co-Authors: Laura Sheard, Nat Mj Wright, Hany G El-sayeh, Clive E Adams, Charlotte Ne TompkinsAbstract:Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares Dihydrocodeine with buprenorphine. Methods Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral Dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. Results 64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received Dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02–2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. Conclusion These findings would suggest that Dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting. Trial registration Current Controlled Trials ISRCTN07752728
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the leeds evaluation of efficacy of detoxification study leeds prisons project a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxification
Substance Abuse Treatment Prevention and Policy, 2009Co-Authors: Laura Sheard, Nat Mj Wright, Clive E Adams, Hany George Elsayeh, Charlotte Ne TompkinsAbstract:Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares Dihydrocodeine with buprenorphine.
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buprenorphine versus Dihydrocodeine for opiate detoxification in primary care a randomised controlled trial
BMC Family Practice, 2007Co-Authors: Nat Wright, Laura Sheard, Clive E Adams, Charlotte Ne Tompkins, Victoria Allgar, Nicola S OldhamAbstract:Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with Dihydrocodeine for detoxification from illicit opiates in primary care.
Clive E Adams - One of the best experts on this subject based on the ideXlab platform.
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ral Substance Abuse Treatment, ssBioMed CentPrevention, and Policy Open AcceResearch The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS)
2016Co-Authors: Laura Sheard, Nat Mj Wright, Hany G El-sayeh, Clive E AdamsAbstract:prisons project: a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxificatio
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The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxification
Substance Abuse Treatment Prevention and Policy, 2009Co-Authors: Laura Sheard, Nat Mj Wright, Hany G El-sayeh, Clive E Adams, Charlotte Ne TompkinsAbstract:Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares Dihydrocodeine with buprenorphine. Methods Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral Dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. Results 64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received Dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02–2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. Conclusion These findings would suggest that Dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting. Trial registration Current Controlled Trials ISRCTN07752728
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the leeds evaluation of efficacy of detoxification study leeds prisons project a randomised controlled trial comparing Dihydrocodeine and buprenorphine for opiate detoxification
Substance Abuse Treatment Prevention and Policy, 2009Co-Authors: Laura Sheard, Nat Mj Wright, Clive E Adams, Hany George Elsayeh, Charlotte Ne TompkinsAbstract:Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares Dihydrocodeine with buprenorphine.
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buprenorphine versus Dihydrocodeine for opiate detoxification in primary care a randomised controlled trial
BMC Family Practice, 2007Co-Authors: Nat Wright, Laura Sheard, Clive E Adams, Charlotte Ne Tompkins, Victoria Allgar, Nicola S OldhamAbstract:Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with Dihydrocodeine for detoxification from illicit opiates in primary care.
Andrew R Moore - One of the best experts on this subject based on the ideXlab platform.
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paracetamol acetaminophen with or without codeine or Dihydrocodeine for neuropathic pain in adults
Cochrane Database of Systematic Reviews, 2016Co-Authors: Philip J Wiffen, Roger Knaggs, Sheena Derry, Peter Cole, Tudor Phillips, Andrew R MooreAbstract:BACKGROUND Paracetamol, either alone or in combination with codeine or Dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. OBJECTIVES To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or Dihydrocodeine for chronic neuropathic pain in adults. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. SELECTION CRITERIA We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or Dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. MAIN RESULTS No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. AUTHORS' CONCLUSIONS There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or Dihydrocodeine, works in any neuropathic pain condition.
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single dose oral Dihydrocodeine for acute postoperative pain
Cochrane Database of Systematic Reviews, 2000Co-Authors: Andrew R Moore, Sheena Derry, Jayne Edwards, H J McquayAbstract:Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances.