Opioids
Humans; Analgesics; Animals; Molecular Sequence Data; Chronic disease; Biomarkers of Pain; Drug Tolerance; Receptors; Amino Acid Sequence; Ligands; Opioid/adverse effects/pharmacology/therapeutic use; Opioid/drug effects
Opioids are the most effective and widely used drugs in the treatment of severe pain. They act through G protein-coupled receptors. Four families of endogenous ligands (opioid peptides) are known. The standard exogenous opioid analgesic is morphine. Opioid agonists can activate central and peripheral opioid receptors. Three classes of opioid receptors (mu, delta, kappa) have been identified. Multiple pathways ofopioid receptor signaling (e.g., G(i/o) coupling, cAMP inhibition, Ca++ channel inhibition) have been described. The differential regulation of effectors, preclinical pharmacology, clinical applications, and side effects will be reviewed in this chapter.
2007
Zollner C; Stein C
Handbook Of Experimental Pharmacology
2007
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).
Journal Article
<a href="http://doi.org/10.1007/978-3-540-33823-9_2" target="_blank" rel="noreferrer">10.1007/978-3-540-33823-9_2</a>
Challenges in using opioids to treat pain in persons with substance use disorders
Humans; Analgesics; Cooperative Behavior; Comorbidity; Long-Term Care; Motivation; Diagnostic and Statistical Manual of Mental Disorders; Primary Health Care; patient care team; Opioid/adverse effects/therapeutic use; Drug Tolerance; Opioid-Related Disorders/diagnosis/epidemiology/etiology/rehabilitation; Pain/drug therapy/epidemiology; Recurrence/prevention & control; Substance Withdrawal Syndrome/diagnosis/etiology; Substance-Related Disorders/epidemiology/rehabilitation
Pain and substance abuse co-occur frequently, and each can make the other more difficult to treat. A knowledge of pain and its interrelationships with addiction enhances the addiction specialist's efficacy with many patients, both in the substance abuse setting and in collaboration with pain specialists. This article discusses the neurobiology and clinical presentation of pain and its synergies with substance use disorders, presents methodical approaches to the evaluation and treatment of pain that co-occurs with substance use disorders, and provides practical guidelines for the use of opioids to treat pain in individuals with histories of addiction. The authors consider that every pain complaint deserves careful investigation and every patient in pain has a right to effective treatment.
2008
Savage SR; Kirsh KL; Passik SD
Addiction Science & Clinical Practice
2008
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Journal Article
<a href="http://doi.org/10.1151/ascp08424" target="_blank" rel="noreferrer">10.1151/ascp08424</a>
Glia: novel counter-regulators of opioid analgesia
Humans; Analgesics; Animals; Opioid/administration & dosage; Drug Tolerance; Brain/drug effects/metabolism; Neuroglia/drug effects/metabolism; Neurotransmitter Agents/metabolism; Nociceptors/drug effects/metabolism; Pain/metabolism/prevention & control; Spinal Cord/drug effects/metabolism
Development of analgesic tolerance and withdrawal-induced pain enhancement present serious difficulties for the use of opioids for pain control. Although neuronal mechanisms to account for these phenomena have been sought for many decades, their bases remain unresolved. Within the past four years, a novel non-neuronal candidate has been uncovered that opposes acute opioid analgesia and contributes to development of opioid tolerance and tolerance-associated pain enhancement. This novel candidate is spinal cord glia. Glia are important contributors to the creation of enhanced pain states via the release of neuroexcitatory substances. New data suggest that glia also release neuroexcitatory substances in response to morphine, thereby opposing its effects. Controlling glial activation could therefore increase the clinical utility of analgesic drugs.
2005
Watkins LR; Hutchinson MR; Johnston IN; Maier SF
Trends In Neurosciences
2005
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Journal Article
<a href="http://doi.org/10.1016/j.tins.2005.10.001" target="_blank" rel="noreferrer">10.1016/j.tins.2005.10.001</a>
Attacking pain at its source: new perspectives on opioids
Humans; Analgesics; Animals; Non-U.S. Gov't; Research Support; Drug Tolerance; Receptors; Ligands; Afferent/metabolism; Cell Movement; Neurons; Opioid Peptides/metabolism/therapeutic use; Opioid/genetics/metabolism; Opioid/metabolism/therapeutic use; Pain/drug therapy/metabolism/therapy; Signal Transduction/physiology
The treatment of severe pain with opioids has thus far been limited by their unwanted central side effects. Recent research promises new approaches, including opioid analgesics acting outside the central nervous system, targeting of opioid peptide-containing immune cells to peripheral damaged tissue, and gene transfer to enhance opioid production at sites of injury.
2003
Stein C; Schafer M; Machelska H
Nature Medicine
2003
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Journal Article
<a href="http://doi.org/10.1038/nm908" target="_blank" rel="noreferrer">10.1038/nm908</a>
Oral opioid therapy for chronic peripheral and central neuropathic pain
Female; Male; Adult; Analgesics; Aged; Outcome Assessment (Health Care); Double-Blind Method; 80 and over; Non-U.S. Gov't; P.H.S.; U.S. Gov't; Chronic disease; Dose-Response Relationship; Drug; Drug Tolerance; Human; Support; Middle Age; Opioid/administration & dosage/adverse effects/therapeutic; use; Central Nervous System Diseases/drug therapy; Levorphanol/administration & dosage/adverse effects/therapeutic use; Neuralgia/drug therapy; Peripheral Nervous System Diseases/drug therapy
BACKGROUND: Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied. METHODS: Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels. RESULTS: Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit. CONCLUSIONS: The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.
2003
Rowbotham MC; Twilling L; Davies PS; Reisner L; Taylor K; Mohr D
New England Journal Of Medicine
2003
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Journal Article
Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics
Child; Female; Humans; Male; Palliative Care; Pain; Adult; Middle Aged; adolescent; Neoplasms/physiopathology; Analgesics/pharmacology; Drug Tolerance; Intractable/therapy; Methadone/therapeutic use; mu/drug effects; Opioid; Receptors
BACKGROUND. Development of tolerance to opioid analgesics occurs often in patients with cancer-related pain. Cross-tolerance among opioid analgesics provides the physician with a major management problem. Incomplete cross-tolerance among opioid analgesics has been demonstrated to occur in animals and humans. The current study provides clinical evidence of the incomplete cross-tolerance of methadone with a number of mu-opioid agonist analgesics in patients with advanced cancer-related pain. RESULTS. Patients presented in the current study had cancer-related pain refractory to other mu--opioid receptor agonist analgesics as evidenced by inadequate analgesia despite escalation of opioid dose. All patients were adequately managed by conversion of their opioid dose to methadone. Additionally, the dose of methadone required to establish and maintain analgesia in these patients was modest compared with previous opioid dose requirements. CONCLUSIONS. Methadone is a potent opioid analgesic that demonstrates incomplete cross-tolerance with other mu-opioid receptor agonist analgesics. Conversion of the opioid-tolerant patient with cancer-related pain to methadone may represent an important therapeutic option in the management of patients with this difficult problem.
Crews JC; Sweeney NJ; Denson DD
Cancer
1993
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Journal Article
<a href="http://doi.org/10.1002/1097-0142(19931001)72:7%3C2266::aid-cncr2820720734%3E3.0.co" target="_blank" rel="noreferrer">10.1002/1097-0142(19931001)72:7%3C2266::aid-cncr2820720734%3E3.0.co</a>
Use of methadone in the morphine-tolerant burned paediatric patient
Child; Female; Humans; Analgesics; Respiration; Methadone; Morphine; infant; Drug Tolerance; Opioid; Artificial; Burns/therapy; Conscious Sedation/methods; Intensive Care/methods
We describe the successful use of methadone in the restoration of sedation and provision of analgesia in two morphine-tolerant, paediatric patients who had suffered significant thermal injuries and were undergoing mechanical ventilation. Both patients had exhibited escalating requirements for sedative drugs while undergoing ventilation yet remained inadequately sedated. The introduction of i.v. methadone in place of i.v. morphine in the sedative regimen rapidly and effectively restored a state of sedation. Hyperalgesia and morphine tolerance appear to be associated; it is proposed that methadone acts primarily, under these circumstances, by re-establishing the analgesic state. Such use of methadone in the morphine-tolerant patient also afforded a concomitant sedative-sparing effect.
1998
Williams PI; Sarginson RE; Ratcliffe JM
British Journal Of Anaesthesia
1998
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Journal Article
<a href="http://doi.org/10.1093/bja/80.1.92" target="_blank" rel="noreferrer">10.1093/bja/80.1.92</a>
Can we use methadone for analgesia in neonates?
Child; Humans; infant; Adult; Analgesics; Methadone; Preschool; Newborn; Drug Tolerance; Analgesia/methods; Opioid/adverse effects
2001
Chana SK; Anand KJ
Archives Of Disease In Childhood. Fetal And Neonatal Edition
2001
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Journal Article
<a href="http://doi.org/10.1136/fn.85.2.f79" target="_blank" rel="noreferrer">10.1136/fn.85.2.f79</a>
Methadone titration in opioid-resistant cancer pain
Female; Male; Pain Measurement; Adult; Analgesics; Aged; Therapeutic Equivalency; Drug Administration Schedule; 80 and over; Administration; Oral; Drug Tolerance; Human; Drug Resistance; Middle Age; Neoplasms/complications; Morphine/administration & dosage; Methadone/administration & dosage; Opioid/administration & dosage; Pain/diagnosis/drug therapy/etiology
AIM: To assess the use of methadone in patients with cancer pain who fail to respond to increasing doses of other opioids or experience intolerable side-effects from them. METHOD: Inpatients of a specialist palliative care unit were titrated onto oral methadone. The dose was calculated as 10% of the previous morphine equivalent dose, up to maximum of 40 mg, given every 3 h as required for analgesia. When daily requirements were stable it was divided into two regular doses. Pain was assessed on a five-point verbal rating score (VRS): a good response was defined as a fall in VRS of two points or more. Results are expressed as median (range). RESULTS: Thirty-three patients (13 men, 20 women, age 61 (34-91) years), 26 with inadequate analgesia and seven with intolerable opioid related side-effects, were converted to methadone from diamorphine (12), morphine (19) or fentanyl (two). Morphine equivalent dose was 480 (20-1200) mg/day prior to titration. Pain was neuropathic (11), nociceptive (three) or mixed (19). Stabilisation on methadone was complete in 3 (2-18) days in 29 (88%) patients at 80 (20-360) mg/day. Twenty-six (78%) had a good response. Four (12%) patients were withdrawn during titration (three entered terminal phase, one failed to respond). During follow-up 15 (45%) required alteration of methadone dose. Twenty-three (70%) patients were discharged home at 12 (4-26) days. In all cases the stable dose of methadone was less than the previous morphine equivalent, and there was a weak correlation between them. CONCLUSIONS: This method of methadone titration often results in improved pain control in patients with morphine resistance or intolerance. It requires careful titration in a specialist inpatient unit as there is no reliable formula for dose equivalence.
1999
Scholes CF; Gonty N; Trotman IF
European Journal Of Cancer Care
1999
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Journal Article
Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit
Child; Intensive Care Units; Risk Factors; Time Factors; Pediatric; Drug Tolerance; Human; Substance Withdrawal Syndrome/diagnosis/drug therapy/etiology; Analgesics/adverse effects; Hypnotics and Sedatives/adverse effects
OBJECTIVE: To describe the consequences of the prolonged administration of sedative and analgesic agents to the pediatric intensive care unit (PICU) patient. The problems to be investigated include tolerance, physical dependency, and withdrawal. DATA SOURCES: A MEDLINE search was performed of literature published in the English language. Cross-reference searches were performed using the following terms: sedation, analgesia with PICU, children, physical dependency, withdrawal; tolerance with sedative, analgesics, benzodiazepines, opioids, inhalational anesthetic agents, nitrous oxide, ketamine, barbiturates, propofol, pentobarbital, phenobarbital. STUDY SELECTION: Studies dealing with the problems of tolerance, physical dependency, and withdrawal in children in the PICU population were selected. DATA EXTRACTION: All of the above-mentioned studies were reviewed in the current manuscript. DATA SYNTHESIS: A case by case review is presented, outlining the reported problems of tolerance, physical dependency, and withdrawal after the use of sedative/analgesic agents in the PICU population. This is followed up by a review of the literature discussing current treatment options for these problems. CONCLUSIONS: Tolerance, physical dependency, and withdrawal can occur after the prolonged administration of any agent used for sedation and analgesia in the PICU population. Important components in the care of such patients include careful observation to identify the occurrence of withdrawal signs and symptoms. Treatment options after prolonged administration of sedative/analgesic agents include slowly tapering the intravenous administration of these agents or, depending on the drug, switching to subcutaneous or oral administration.
2000
Tobias JD
Critical Care Medicine
2000
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Journal Article