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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.
Eur J Pain 2005 Apr
PMID:Opioid tolerance and dependence -- do they matter? 1573 7

New effective analgesics are needed for the treatment of pain. Buprenorphine, a partial mu-opioid agonist which has been in clinical use for over 25 years, has been found to be amenable to new formulation technology based on its physiochemical and pharmacological profile. Buprenorphine is marketed as parenteral, sublingual, and transdermal formulations. Unlike full mu-opioid agonists, at higher doses, buprenorphine's physiological and subjective effects, including euphoria, reach a plateau. This ceiling may limit the abuse potential and may result in a wider safety margin. Buprenorphine has been used for the treatment of acute and chronic pain, as a supplement to anesthesia, and for behavioral and psychiatric disorders including treatment for opioid addiction. Prolonged use of buprenorphine can result in physical dependence. However, withdrawal symptoms appear to be mild to moderate in intensity compared with those of full mu agonists. Overdoses have primarily involved buprenorphine taken in combination with other central nervous system depressants.
J Pain Symptom Manage 2005 Mar
PMID:Buprenorphine: considerations for pain management. 1578 Nov 80

Opioid analgesics are the standard therapeutic agents for the treatment of pain, but their prolonged use is limited because of the development of tolerance and dependence. Recently, we reported the development of a mu-opioid receptor knock-in (KI) mouse in which the mu-opioid receptor was replaced by a mutant receptor (S196A) using a homologous recombination gene-targeting strategy. In these animals, the opioid antagonist naltrexone elicited antinociceptive effects similar to those of partial agonists acting in wild-type (WT) mice; however, development of tolerance and physical dependence were greatly reduced. In this study, we test the hypothesis that the failure of naltrexone to produce tolerance in these KI mice is attributable to its simultaneous inhibition of delta-opioid receptors and activation of mu-opioid receptors. Simultaneous implantation of a morphine pellet and continuous infusion of the delta-opioid receptor antagonist naltrindole prevented tolerance development to morphine in both WT and KI animals. Moreover, administration of SNC-80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide], a delta agonist, in the naltrexone-pelleted KI animals resulted in a dose-dependent induction in tolerance development to both morphine- and naltrexone-induced analgesia. We conclude that although simultaneous activation of both mu- and delta-opioid receptors results in tolerance development, mu-opioid receptor activation in conjunction with delta-opioid receptor blockade significantly attenuates the development of tolerance.
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PMID:In vivo activation of a mutant mu-opioid receptor by naltrexone produces a potent analgesic effect but no tolerance: role of mu-receptor activation and delta-receptor blockade in morphine tolerance. 1578 80

Pain management using opioid analgesics strives to achieve three goals: maximum efficacy, minimal risk of tolerance and physical dependence, and negligible side effects. Following the cloning of opioid and nociceptin receptors, novel ligands can be designed to target specific residues of these membrane proteins with the goal of improving efficacy and reducing side effects through selectivity. For the most part, ligand design has focused on binding sites located in the transmembrane region of the receptors, and has ignored the extracellular domains. In this review, we discuss the evidence for the interaction of the extracellular regions with opioids and show how computational biology tools can be used to model these domains for use in drug discovery. A computational model of the kappa-opioid receptor which includes the loop regions is presented. The model combines knowledge-based information, bioinformatics and computational tools to identify regions of the extracellular loop domains that can be targeted by drug design.
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PMID:The function of the extracellular regions in opioid receptor binding: insights from computational biology. 1585 17

Contemporary standard pharmacological care for the treatment of noncancer pain includes the use of opioid medications. The responsiveness of neuropathic pain to opioids has long been an area of controversy. Evidence from multiple randomized controlled trials indicates that opioids can relieve pain in a variety of neuropathic pain syndromes. Opioids are typically reserved for moderate to severe pain that cannot be relieved by the nonsteroidal anti-inflammatory drugs (NSAIDs). Opioids are often used in combination with other adjuvants or other analgesic agents. The advantage of opioids is the lack of a ceiling effect of the pure mu opioid agonists. The disadvantages of these drugs are a series of mechanism-based opioids-related side effects (e.g., nausea, drowsiness, constipation) and the potential issue of their abuse and misuse. Each patient needs to undergo a comprehensive evaluation and receive education on the treatment. The physician must be well conversant with the differential diagnosis and definitions of physical dependence, tolerance, pseudotolerance, aberrant behaviors, addiction, and pseudoaddiction. No specific opioid drug is intrinsically ''better'' than the others. Opioid rotation refers to the switch from one opioid to another when the degree of analgesia obtained is limited by the persistence of adverse effects or the occurrence of clinically relevant tolerance. This approach is based on the observation that a patient's response varies from opioid to opioid. At present, after 1) appropriate selection of patients and 2) longitudinal patient care with routine assessment of degree of analgesia, functional daily activities, adverse events and aberrant behaviors is carried out, opioid therapy can be the safest and most effective treatment measure for quality of life improvement in the chronic pain patient.
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PMID:Opioid therapy for chronic noncancer pain: practice guidelines for initiation and maintenance of therapy. 1601 15

Chronic opioid use in the management of pain is limited by development of analgesic tolerance and physical dependence. The mechanisms underlying tolerance-dependence are not entirely clear, however, recent evidence suggests that spinal adaptations leading to increased activity of sensory neuropeptides (calcitonin gene-related peptide (CGRP), substance P) and their downstream signaling messengers derived from metabolism of arachidonic acid: prostaglandins (PG), lipoxygenase (LOX) metabolites, and endocannabinoids, plays an important role in this phenomenon. In this communication we review the evidence implicating these factors in the induction and expression of opioid tolerance and physical dependence at the spinal level.
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PMID:The spinal basis of opioid tolerance and physical dependence: Involvement of calcitonin gene-related peptide, substance P, and arachidonic acid-derived metabolites. 1604 75

The impact of poorly managed chronic pain on the quality of life of elderly patients and the problems related to its management are widely acknowledged. Underutilisation of opioids is a major component of poor pain management in this group of patients, despite good evidence for the effectiveness of opioids and published guidelines directing their usage. Reasons for this underutilisation are, among others, poor assessment of pain in this age group; fear of polypharmacy and opiophobia; and avoidance of opioids because of concerns about tolerance, physical dependence, addiction and adverse effects. This review suggests approaches to overcome these barriers to opioid usage, such as regular pain assessments, education to overcome opiophobia, rational prescribing, utilisation of less conventional opioids and non-oral routes of administration, avoidance of inappropriate opioids, opioid rotation, and education about managing or preventing adverse effects, the reasons why opioid therapy may be unsuccessful, and the effects of psychological factors on the pain experience. This more rational and knowledge-based approach to the use of opioids in the management of chronic pain in the elderly population should correct the current problems with underprescribing in this age group.
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PMID:Underutilisation of opioids in elderly patients with chronic pain: approaches to correcting the problem. 1606 Jul 15

Persons experiencing pain, whether acute or chronic, seek and deserve relief from their discomfort and loss of function. However, opioid analgesics have the capacity to induce tolerance, physical dependence, and addiction. Furthermore, persons with a history of opioid use disorders or other substance misuse problems are at "high risk" when they acquire painful conditions requiring aggressive treatment. Prescription of opioids could trigger a relapse to the original drug of choice or could initiate a new bout of addiction with the prescribed drug. This article explores the relationship between addiction and pain, including signs of developing addiction and approaches to managing pain in those with addiction.
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PMID:Addiction and the treatment of pain. 1628 84

Critically ill patients, particularly those under mechanical ventilation, require analgo-sedation to control noxious stimuli and enhance comfort. Despite their harmful side effects, such as respiratory depression, physical dependence and difficult arousal, opioids are effective in providing a good level of analgesia and comfort. Traditional opioids (morphine and fentanyl) have been shown effective in providing analgesia; however, the respiratory adverse effects and their pharmacokinetics, with an high risk of accumulation, limits their use, especially for a long-term sedation. In the last decade, new synthetic opioids with limited side effects and favourable pharmacokinetics profile, such as Sufentanil and Remifentanil, have been investigated to evaluate their efficacy in mitigating pain and enhancing comfort in critically ill patients.
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PMID:Analgesia in PACU: intravenous opioids. 1630 48

Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Although common concerns regarding the use of opioids include the potential for detrimental side effects, physical dependence, and addiction, accumulating evidence suggests that opioids may yet cause another problem, often referred to as opioid-induced hyperalgesia. Somewhat paradoxically, opioid therapy aiming at alleviating pain may render patients more sensitive to pain and potentially may aggravate their preexisting pain. This review provides a comprehensive summary of basic and clinical research concerning opioid-induced hyperalgesia, suggests a framework for organizing pertinent information, delineates the status quo of our knowledge, identifies potential clinical implications, and discusses future research directions.
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PMID:Opioid-induced hyperalgesia: a qualitative systematic review. 1650 5


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