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Text
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<a href="http://doi.org/10.2165/00003088-199733030-00005" target="_blank" rel="noreferrer">http://doi.org/10.2165/00003088-199733030-00005</a>
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Title
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Pharmacokinetic optimisation of opioid treatment in acute pain therapy
Publisher
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Clinical Pharmacokinetics
Date
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1997
Subject
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Humans; Pain; Analgesics; Drug Interactions; Analgesia; Drug Administration Schedule; Administration; Oral; Pain/drug therapy; Infusions; Injections; Intravenous; Dose-Response Relationship; Drug; Subcutaneous; Intramuscular; Patient-Controlled; Postoperative/drug therapy; Substance-Related Disorders; Opioid/pharmacokinetics/pharmacology/therapeutic use; Central Nervous System/drug effects/metabolism
Creator
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Upton RN; Semple TJ; Macintyre PE
Description
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Traditionally, opioids have been administered as fixed doses at fixed dose intervals. This approach has been largely ineffective. Patient-controlled analgesia (PCA) and upgraded traditional approaches incorporating flexibility in dose size and dose interval, and titration for an effect in individual patients with the monitoring of pain and sedation scores, can greatly improve the efficacy of opioid administration. Optimising opioid use, therefore, entails optimising the titration process. Opioids have similar pharmacodynamic properties but have widely different kinetic properties. The most important of these is the delay between the blood concentrations of an opioid and its analgesic or other effects, which probably relate to the delay required for blood and brain and spinal cord (CNS) equilibrium. The half-lives of these delays range from approximately 34 minutes for morphine to 1 minute for alfentanil. The titration is influenced by the time needed after an initial dose before it is safe to administer a second dose and the duration of the effects of a single dose, which varies widely between opioids, doses and routes of administration. To compare opioids and routes of administration, we examined the relative CNS concentration profiles of opioids - the CNS concentration expressed as a percentage of its maximum value. The relative onset was the defined as the time the relative CNS concentration first rose to 80% of maximum, while the relative duration was defined as the length of time the concentration was above 80%. For an intravenous bolus dose, the relative onset varies from approximately 1 for alfentanil to 6 minutes for morphine, while their relative durations are approximately 2 and 96 minutes, respectively. Although all of the common opioids, perhaps with the exception of alfentanil, have kinetic and dynamic properties suitable for use in PCA with intravenous bolus doses, the long relative duration of morphine makes it particularly suited to an upgraded traditional approach using staff administered intramuscular or subcutaneous doses. There is a clear kinetic preference for regimens with a rapid onset and short duration (e.g. intravenous PCA) for coping with incident pain. It is shown that, in general, titration is improved by the more frequent administration of smaller doses, but it is important to use additional doses to initially 'load' a patient. The titration of opioids should always be accompanied by the monitoring of pain and sedation scores and ventilation.
1997
Identifier
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<a href="http://doi.org/10.2165/00003088-199733030-00005" target="_blank" rel="noreferrer">10.2165/00003088-199733030-00005</a>
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Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Type
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Journal Article
1997
Administration
Analgesia
Analgesics
Backlog
Central Nervous System/drug effects/metabolism
Clinical Pharmacokinetics
Dose-Response Relationship
Drug
Drug Administration Schedule
Drug Interactions
Humans
Infusions
Injections
Intramuscular
Intravenous
Journal Article
Macintyre PE
Opioid/pharmacokinetics/pharmacology/therapeutic use
Oral
Pain
Pain/drug Therapy
Patient-Controlled
Postoperative/drug therapy
Semple TJ
Subcutaneous
Substance-Related Disorders
Upton RN