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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid dependent patients require higher than normal doses of opioid analgesics. However, this regimen has not been formally tested. This study utilised a double-blind placebo-controlled design to examine antinociceptive responses to saline and pseudo-steady-state plasma morphine concentrations (173+/-11 (mean+/-SEM), range 106-305 ng/ml) in 18 methadone participants in three stable, once daily methadone dose ranges 11-45 mg (n=6), 46-80 mg (n=6), 81-115 mg (n=6) and 10 controls. Testing commenced approximately 20 h after the maintenance dose with the next dose given 1h after morphine cessation. Nociceptive stimuli (cold pressor (seconds) and electrical stimulation (volts)) were used to measure pain detection threshold and pain tolerance. Blood samples were analysed by HPLC for plasma morphine and R-(-)-methadone concentrations. Methadone participants were hyperalgesic to cold pressor pain. High plasma morphine concentrations failed to significantly change cold pressor and electrical stimulation pain tolerance for methadone patients, but in controls, morphine significantly (P<0.05) increased mean pain tolerance to cold pressor by 59+/-29% (range -17% to 311%) and electrical stimulation by 19+/-6% (range 0% to 58%). Morphine significantly (P<0.05) decreased respiration rates by 12+/-3% (range -29% to 8%) in methadone subjects. On saline days, rising methadone concentrations significantly (P<0.01) increased cold pressor pain detection threshold by 32+/-6% (range 1-81%) and cold pressor pain tolerance by 23+/-6% (range -32% to 56%). Methadone maintained patients are hyperalgesic and cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. While even higher morphine doses may achieve some pain relief, this may be at the cost of unacceptable respiratory depression.
Pain 2006 Feb
PMID:Methadone maintenance patients are cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. 1642 97

Methadone is a synthetic opioid that is effective for the relief of moderate-to-severe pain and for the treatment of opioid dependence. The pharmacokinetics of methadone differ from those of morphine in that methadone has a higher bioavailability, a much longer half-life, and is hepatically metabolized by cytochrome P450 enzymes. The pharmacokinetics of methadone are variable and an understanding of the factors that impact the onset, magnitude, and duration of analgesia is required to optimize therapy. Drug interactions are common and patients receiving methadone should be monitored closely for toxicity or therapeutic failure. Special populations in whom a change from the usual dosage regimen may be necessary include pediatric patients, patients with renal failure, the elderly, and pregnant women. To achieve an optimal dosage regimen, the clinician must have an understanding of the pharmacokinetics and pharmacodynamics of methadone in addition to the relationship between these variables and their patients' demographic and pathophysiologic characteristics. AMEDLINE search was performed to identify literature published between 1966 and May 2005 relevant to the pharmacokinetics of methadone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of methadone disposition including its absorption profile, distribution, and metabolism/excretion. General dosing guidelines, dosage conversions from other opioids and pharmacokinetic issues in special populations are discussed.
J Pain Palliat Care Pharmacother 2005
PMID:Pharmacokinetics of methadone. 1643 29

Pain is not the most frequent symptom in cancer patients, but it is considered the most serious and threatening symptom. Opioid analgesics are the mainstay for analgesic treatment of cancer patients. Methadone is increasingly being considered as an alternative to morphine and seems to become relatively more potent with increasing exposure to other opioids. "Newer" side effects of opioids have been demonstrated, including cognitive impairment, generalized allodynia/hyperalgesia, myoclonus and hallucinations. When the pain relief effects of oral opioids have been exhausted, other pain management approaches, including spinal delivery of analgesics, may be effective alternatives.
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PMID:[Cancer-related pain]. 1676 93

Methadone maintenance is associated with hyperalgesia and elevated mood disturbance-effects opposite to those induced by acute opioid administration, which may undermine outcomes during substitution therapy. This study examined the impact of switching between methadone and slow-release morphine on pain sensitivity and mood status in 14 methadone maintenance patients using an open-label crossover design. Pain responses were nearly identical for each drug. Patients reporting inadequate withdrawal suppression on methadone showed greater mood stability when transferred to morphine, but overall mood disturbance levels did not differ between drugs. Hyperalgesia and mood disturbance cannot be resolved by changing from methadone to morphine maintenance.
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PMID:Switching between methadone and morphine for maintenance treatment of opioid dependence: impact on pain sensitivity and mood status. 1686 27

Increasing numbers of patients with chronic kidney disease Stage 5 (GFR <15ml/minute) are being managed without dialysis, either through their own preference or because dialysis is unlikely to benefit them. This growing group of patients has extensive health care needs. Their overall symptom burden is high, and symptom prevalence matches or exceeds that in other end of life populations, both with cancer and other non-cancer diagnoses. These symptoms may often go unrecognised and under-treated. Regular symptom assessment is necessary, together with pro-active management of identified symptoms. Pain can be managed using the principles of the World Health Organisation analgesic ladder. Not all opioid medications are recommended for these patients. Paracetamol, tramadol, and fentanyl are the most appropriate medications for steps 1, 2 and 3 respectively. There is limited evidence on the use of buprenorphine, oxycodone and hydromorphone. Methadone is safe but should only be prescribed by a clinician experienced in its use. Morphine and diamorphine are not recommended because of metabolite accumulation. Pruritus is also challenging to manage. The evidence for pharmacological interventions to alleviate pruritus is summarized, and a pragmatic approach to management suggested. Emollients, capsaisin cream, antihistamines, thalidomide and ondansetron may be helpful, according to the extent and pattern of pruritus. Symptoms may frequently be due to co-morbid conditions, not renal disease itself, and managing them is difficult because of the constraints on the use of medication which kidney failure imposes. Collaboration between renal and palliative specialists can help identify ways to achieve best care for these patients.
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PMID:Symptom management in patients with established renal failure managed without dialysis. 1689 2

Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit opioids and in the treatment of pain. A sensitive and selective high-performance liquid chromatographic method with diode array detection for the simultaneous determination of methadone, buprenorphine and norbuprenorphine has been developed. Separation of the three analytes was obtained by using a reversed-phase column (C8, 250mmx4.6mm i.d., 5microm) and a mobile phase composed of 40% phosphate buffer containing triethylamine, 50% methanol and 10% acetonitrile (final apparent pH 6.0). Loxapine was used as the internal standard. An accurate pre-treatment procedure of biological samples was developed, using solid-phase extraction with C8 cartridges (100mg, 1mL) and needing small amounts of plasma or urine (300microL). The calibration curves were linear over a working range of 10.0-1500.0ng/mL for methadone and of 5.0-500.0ng/mL for buprenorphine and norbuprenorphine in both matrices. The limit of quantitation (LOQ) and the limit of detection (LOD) were 1.0 and 0.4ng/mL for methadone and 0.5 and 0.2ng/mL for both buprenorphine and norbuprenorphine, respectively. The method was successfully applied to the analysis of plasma and urine samples from patients undergoing treatment with these drugs. Precision and accuracy results were satisfactory and no interference from endogenous or exogenous compounds was found. The method is suitable for the simultaneous determination of methadone and buprenorphine in human plasma and urine for therapeutic drug monitoring purposes.
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PMID:Simultaneous determination of methadone, buprenorphine and norbuprenorphine in biological fluids for therapeutic drug monitoring purposes. 1704 38

Methadone is used as an alternative opioid when first line opioids fail to provide adequate pain control. Highly variable morphine:methadone dose ratios make switching challenging and little is known about the pharmacokinetics of long lasting methadone treatment for pain. Twelve patients treated with morphine for chronic non-malignant pain were switched to methadone. Seven of these patients continued with methadone throughout the nine months study period and only minor dose adjustments were performed. Serum concentrations of morphine, methadone and their metabolites were measured at baseline, day one and two, after dose titration and one week, five weeks, three months and nine months after the end of dose titration. Serum concentrations of methadone and its metabolite EDDP did not change significantly from the end of dose titration and during the nine months (repeated measures ANOVA: p=0.88 and p=0.06). Very low correlation between dose ratios and serum concentration ratios between morphine and methadone was observed. Large interindividual differences in serum concentrations and metabolism were observed. Our findings contradict that autoinduction of methadone metabolism takes place during long term treatment and supports that a 3-day opioid switch from morphine to methadone followed by a one week titration seems pharmacologically sound.
Eur J Pain 2007 Aug
PMID:Long term methadone for chronic pain: a pilot study of pharmacokinetic aspects. 1711 29

Methadone is a unique mu opioid agonist, which also has delta receptor affinity and properties of N-methyl-D-aspartate receptor antagonism and monoamine reuptake inhibition. It is mainly used in the setting of uncontrolled pain or dose-limiting toxicity. Caution is advised when switching to methadone, especially from high doses of previous opioid, due to its variable conversion ratio and the potential for delayed toxicity due to its long half-life. Increasing evidence of risk also exists for a prolonged QT interval and torsades de pointes with very large doses of methadone. Methadone is likely safer when used at lower doses as a first-line opioid, but its potential as such has not received enough formal evaluation. Randomized controlled trials are needed to assess the effectiveness and safety of methadone compared with other opioids and to further evaluate its role in the treatment of neuropathic pain.
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PMID:Methadone for treatment of cancer pain. 1725 28

While methadone has been available for over 50 years, its use in opiate dependence has overshadowed its use as an analgesic. Within the last 10-15 years, though, methadone has been increasingly used to manage neuoropathic pain and cancer pain, but its use is causing an alarming number of deaths in the U.S. Last June, The Charleston Gazette ran a series titled "The Killer Cure" by Scott Finn and Tara Tuckwiller that found that the number of Americans whose deaths were caused by methadone rose from 790 in 1999 to 2,992 in 2003. The series also reported other statistics from the National Center for Health Statistics that revealed that West Virginia ranked first per capita in methadone overdose deaths, and that methadone was more likely involved in overdose deaths than any other prescription drug. Methadone has several unique properties that can be beneficial in the treatment of neuropathic pain and cancer pain unresponsive to other opioids, but some of these properties make it very dangerous and difficult to prescribe properly. As a result of these factors, methadone should not be the first-choice drug for pain and it should not be used in opioid-naive patients. The goal of this article is to provide a review of the properties and protocols for safe prescribing of methadone to help physicians recognize situations where this drug offers the greatest advantage as an analgesic.
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PMID:Methadone as an analgesic: a review of the risks and benefits. 1743 10

Opioid switching is often used to improve the opioid response in patients with cancer experiencing poor analgesia or adverse effects. When switching between drugs with delayed effect because of pharmacokinetics or type of delivery, concerns exist about the correct timing of introducing the second drug after stopping the previous one. The aim of this study was to assess plasmatic changes of fentanyl and methadone underlying the clinical events occurring during opioid switching. Eighteen patients with cancer receiving transdermal fentanyl with uncontrolled pain and/or moderate to severe opioid adverse effects, were switched to oral methadone using an initial fixed ratio of 1:20. Fentanyl patches were removed and the first of three daily doses of methadone was started concurrently. Blood samples were obtained at intervals after removing the fentanyl patch, and at 5-hour intervals for the first 25 hours. The intensity of pain and the adverse effects were assessed before switching, the day after, and then daily up to dose stabilization. A successful switch was considered when the intensity of pain and distress score decreased at least of 33% of the basal value recorded before the switch, within a reasonable period of time. Complete blood samples were obtained in 16 patients. Methadone plasma concentration increased from 2 to 245 ng/mL, and fentanyl plasma concentration decreased from 15 to 8 ng/mL, 25 hours after. A successful switch was determined the day after in 7 patients, while 4 patients did not respond favorably (effective switching, 63%). Five patients were considered too terminal for an appropriate evaluation. No differences in plasma concentration pattern of the two opioids were found between patients considered responders and nonresponders. Conversion ratios between opioids at time of stabilization did not significantly change in comparison with the initial conversion ratio chosen. Starting methadone soon after removing fentanyl patches results in a rapid increase of methadone concentration, while the half-life of transdermal fentanyl is reached after 25 hours. As a result, the rapid achievement of a clinical effect is obtained avoiding distressing therapeutic holes in patients with a clinical condition, mainly characterized by poor pain control and severe adverse effects, requiring an immediate intervention.
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PMID:Opioid plasma concentrations during a switch from transdermal fentanyl to methadone. 1747 4


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