Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fentanyl is a synthetic opioid with short-acting analgesic activity after intravenous or subcutaneous administration. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery via the transdermal therapeutic system (TTS). These systems are designed to release the drug into the skin at a constant rate ranging from 25 to 100 micrograms/h, multiple systems can be applied to achieve higher delivery rates. Initially, much of the clinical experience with fentanyl TTS was obtained in patients with acute postoperative pain. However, because of the increased risk of respiratory complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide including the US, its use is not restricted to chronic cancer pain; the drug is also available for treatment of general chronic pain, including that of nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation of the drug within skin tissue results in a significant delay (17 to 48 hours) before maximum plasma concentration is achieved. Approximately half of the cancer patients converted to transdermal fentanyl from other opioid agents required increased dosages after initial application of the patch. However, concomitant use of short-acting morphine maintained pain relief during the titration period, and the use of such supplementary medication decreased with the duration of fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50% decrease (less pain) during transdermal fentanyl therapy compared with previous opioid treatment. In addition, patient preference for fentanyl TTS was indicated by the number of patient requests (up to 95%) for continued use of the drug at the end of the study. Although fentanyl TTS is contraindicated in patients postoperatively, the efficacy of fentanyl via the transdermal route was investigated in this patient group. Supplementary patient controlled analgesia was significantly reduced in patients who received fentanyl TTS 75 micrograms/h compared with placebo, although this was not apparent until > or = 12 hours after application. Data evaluating pain relief, which was assessed by VAS pain scores, were inconclusive. Preliminary data, although from relatively small numbers of patients, indicate that transdermal fentanyl may be useful in the management of chronic non-malignant pain. Indeed, some patients whose pain was previously uncontrolled became completely pain free. The most frequently occurring adverse events during fentanyl TTS therapy (as with other opioid agents) included vomiting, nausea and constipation, although vomiting and nausea were not clearly associated with the drug. The most serious adverse event was hypoventilation, which occurred more frequently in postoperative (4%) than in cancer patients (2%). In surgical patients, fentanyl-associated respiratory events (reduced respiratory rate and apnoea) generally occurred within 24 hours of patch application; however, there were isolated reports of late onset (> or = 36 hours postsurgery) fentanyl-associated respiratory depression. In cancer patients, the incidence of constipation was reduced by up to two-thirds after switching from oral morphine to transdermal fentanyl. Transient skin irritation associated with the plastic patch or the adhesive, rather than the drug, was reported in a maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative to other opioid agents, which are also recommended on the third step of the WHO analgesic ladder, in the management of chronic malignant pain. Preliminary data indicate that it may be useful in the management of chronic nonmalignant pain. The advantages offered by fentanyl TTS over traditional methods of chronic pain control include its ease of administration, less constipation and the 3-
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PMID:Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. 901 Jun 52

We compared patient-controlled epidural analgesia (PCEA) with patient-controlled intravenous analgesia (PCIA) using pethidine or fentanyl in a randomized, double-blind crossover study of 80 patients after caesarean section. Patients received pethidine by PCEA or PCIA, or fentanyl by PCEA or PCIA, with a crossover of the route of administration at 12h. For pethidine, pain scores were lower with PCEA vs PCIA from 4 to 16h (P < 0.05). Pethidine consumption was lower with PCEA vs PCIA from 12 to 24h (P = 0.0005). Patients preferred PCEA to PCIA (P = 0.015). For fentanyl, pain scores were lower with PCEA vs PCIA at 12h (P = 0.045). Fentanyl consumption was lower with PCEA vs PCIA from 0 to 12h (P = 0.0007). Patients had similar preference for PCEA and PCIA. Pain scores and side-effects were similar between drugs. Plasma pethidine was similar between groups. Plasma fentanyl was higher with PCIA vs PCEA at 12h (P = 0.002). PCEA has advantages over PCIA and pethidine may be the preferred drug.
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PMID:Comparison of patient-controlled epidural analgesia with patient-controlled intravenous analgesia using pethidine or fentanyl. 912 53

Inoperable bowel obstruction in patients with renal failure is a difficult clinical situation. In the last days of life, an accumulation of morphine metabolites in patients with impaired renal function may cause opioid toxicity, including terminal agitation. The use of an alternative drug may prevent morphine metabolite accumulation in uremic patients. Fentanyl may be an alternative to morphine. It has a large apparent volume of distribution, a short plasma half-life, and extensive biotransformation without active metabolites. A patient with acute renal impairment and bowel obstruction was successfully treated with a subcutaneous continuous infusion of fentanyl (25 micrograms/hr) and boluses of 12.5 micrograms for the last 2 days of life, limiting the worsening of the dramatic clinical picture of bowel obstruction combined with renal impairment. No local toxicity was evidenced.
J Pain Symptom Manage 1997 Apr
PMID:Subcutaneous fentanyl infusion in a patient with bowel obstruction and renal failure. 913 36

Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.
J Pain Symptom Manage 1997 May
PMID:Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. 976 15

A new method of administration of an opioid was recently registered: fentanyl transdermal (brand name: Durogesic), intended particularly for the indication range 'pain in cancer'. Fentanyl is lipid-soluble so that deposition in the skin takes place and the biological half-life is approximately 20 hours after removal of the plaster. It is safe to start on a basis of an equianalgesic conversion of 100:1 in relation to oral morphine, although this may entail some risk of fentanyl under dosage. The dose adjustment time is 12-24 hours before a constant fentanyl level is reached; therefore, after attaching the first sticking plaster, the original morphine dose should be continued for another 12 hours. In addition, the patient may, if necessary, be given supplementary morphine preferably as a short-acting drug. There seems to be no clear indication for transdermal fentanyl either in neuropathic pain or in chronic benign pain.
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PMID:[Transdermal opioid administration: the pain plaster]. 938 Jan 79

Stinus et al. [L. Stinus, M. Auriacombe, J. Tignol, A. Limoge, M. Le Moal, Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies, Pain, 42 (1990) 351-363.] observed that transcranial electrical stimulation (TCES) with high-frequency intermittent current potentiated opiate-induced analgesia using the tail-flick test. In unanesthetized, chronic preparations, electrical stimulation (0.5 Hz) of the lower incisor pulp of rats elicits a short-(6 ms) and a long-latency (12-18 ms) jaw-opening reflex (JOR) without any evidence of aversive behavior [J. Azerad, F. Fuentes, I. Lendais, A. Limoge, B. Pollin, Methods for selective tooth pulp stimulation in acute and chronic preparations in rats, J. Physiol., 406 (1988) 3P.]. Fentanyl increases thresholds of both reflexes and transiently suppresses the long-latency JOR. We then decided to look at the influence of TCES on both drug-induced mean of maximal threshold variation (MMTV) and duration of JOR suppression period. These parameters have been investigated in 43 Wistar rats with or without TCES administered for 3 h before the drug injection and throughout the testing period. TCES alone has no effect. In contrast, it significantly increases the duration of the reflex suppression period (149 +/- 5% vs. control, P < 0.001) while fentanyl-increased reflex thresholds remain unchanged. The fentanyl-induced JOR suppression period returns to the control values 2 days later. When a second 3-h TCES session is delivered 2 or 4 days after the first TCES session, a similar increase of this suppression period is observed. Moreover, 2 days after a second TCES session, an increase of the duration of the fentanyl-induced JOR suppression period is systematically observed. In contrast, a 6-h TCES session never induces such effects. These results confirm a potentiating effect of TCES on opioid action and demonstrate the value of repeated TCES sessions.
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PMID:Potentiation of fentanyl suppression of the jaw-opening reflex by transcranial electrical stimulation. 927 23

This study compared recovery characteristics and postoperative ventilatory function when halothane, fentanyl or combination of halothane and fentanyl in addition to N2O were used for intraoperative anaesthesia in term infants undergoing hernia repair as outpatients. Sixty-six full term ASA PS I infants ages 1-12 months were studied. All received inhalation induction with N2O, O2 and halothane, followed by intravenous atropine and atracurium, tracheal intubation, and controlled ventilation. For anaesthesia maintenance, patients were randomized into one of three groups. Group I received 70% N2O, 30% O2 and halothane. Group II received 70% N2O, 30% O2, halothane and 2 micrograms.kg-1 fentanyl. Group III received 70% N2O, 30% O2 and 10 micrograms.kg-1 fentanyl. Awakening times were similar in all three groups, however, Group I patients had significantly shorter recovery and discharge times than those of Group II and III. None of the patients experienced postoperative apnoea or periodic breathing. One patient in Group III experienced two brief episodes of bradycardia not associated with apnoea or arterial desaturation (SpO2 > 90% for greater than 30 s). Decreased SpO2 occurred less frequently in Group I (5.9%) compared to Group II (22.7%) and Group III (19.0%) patients, however, the group differences were not significant. Transcutaneous CO2 (TcCO2) values were not statistically different among the three groups. Pain scores were initially lower in Groups II and III, but at 120 min the differences were not significant. Postoperative apnoea was not observed in this study. SpO2 < 90% and TcCO2 > 9 kPa (70 mmHg) was more common in infants receiving 2 and 10 micrograms.kg-1 fentanyl than in infants receiving halothane and nitrous oxide anaesthesia. Infants < 3 months old did not have a higher incidence of SpO2 < 90% or significantly higher TcCO2 values when compared to infants > 3 months old. Fentanyl in doses used in this study did not prolong awakening time but did prolong recovery and discharge times in outpatient infants.
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PMID:Evaluation of awakening and recovery characteristics following anaesthesia with nitrous oxide and halothane fentanyl or both for brief outpatient procedures in infants. 930 63

Fentanyl, and its structural analogs lofentanil and sufentanil, are potent analgesics used clinically in the management of pain. However, the high analgesic potency of these compounds is limited by the development of tolerance after chronic use. To investigate whether their tolerance development may be related to mu receptor desensitization, the cloned mouse mu receptor as well as mutant forms of the receptor were stably expressed in HEK 293 cells and tested for their response to continuous opioid treatment. Fentanyl and its analogs potently bound to the mu receptor and effectively inhibited cAMP accumulation. Three-hour pretreatment of mu receptors with fentanyl and its analogs desensitized the mu receptor by uncoupling it from adenylyl cyclase. The fentanyl analogs caused a slight internalization of the mu receptor as accessed by antibody binding to the epitope-tagged mu receptor. Truncation of the mu receptor by removal of its carboxyl terminus at Glu341 did not affect the ability of the fentanyl analogs to bind to and activate the mu receptor nor did it prevent the fentanyl analogs from desensitizing the receptor. In a previous study we showed that morphine did not desensitize the cloned mu receptor even though it is a potent and effective agonist at the mu receptor. Mutagenesis studies revealed that morphine interacts differently with the mu receptor to activate it than do the fentanyl analogs which may explain its lack of desensitization of the mu receptor. These results indicate that desensitization of the mu receptor may be a molecular basis for the development of tolerance to fentanyl and its analogs.
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PMID:Fentanyl and its analogs desensitize the cloned mu opioid receptor. 961 24

A transdermal fentanyl patch for the treatment of chronic cancer-related pain is available in four dosages (25, 50, 75, and 100 microg/hr). Fentanyl is released from a 72-hour reservoir by diffusion through a controlled-release membrane to the skin, through which it is absorbed into the microcirculation. The pharmacokinetics of fentanyl differ markedly as a function of the route of administration. Unlike intravenous administration, in which peak plasma levels occur within minutes and the plasma elimination half-life is 2 to 3 hours, after initial transdermal fentanyl patch application, peak levels occur within 14 hours and the elimination half-life exceeds 24 hours. When compared with oral morphine at doses effecting the same degree of pain relief, fewer gastrointestinal disturbances (nausea, vomiting, and constipation) and better alertness and sleep quality have been reported in two studies. The transdermal fentanyl patch is as effective as oral opioids in relieving cancer-related pain, with a safety and side effect profile equal to or better than that of oral opioids. The convenient, once-every-72 hours dosing regimen is easily adjusted to the individual's need for around-the-clock pain control, and provides stable and predictable therapeutic drug plasma concentrations. Patient acceptability is high and the cost is lower than other methods required to deliver parenteral opioids. The recent development of an oral transmucosal fentanyl citrate delivery system for the treatment of breakthrough pain will further expand the use of transdermal fentanyl patches for the treatment of chronic pain.
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PMID:Factors influencing quality of life in cancer patients: the role of transdermal fentanyl in the management of pain. 967 31

Fentanyl has been incorporated into a transdermal therapeutic system (TTS) containing a rate-limiting membrane that provides constant release of the opioid. TTS fentanyl provides continuous opioid delivery for up to 72 hr without the need for special equipment. After Institutional Review Board approval, 53 patients with cancer pain requiring 45 mg or more of oral morphine daily were admitted into an open-label, prospective, multicenter evaluation of TTS fentanyl for the relief of pain. After a 1-week stabilization on oral morphine, patients were transferred from morphine to an appropriate dose of TTS-fentanyl (25, 50, 75, or 100 micrograms/hr) administered as a transdermal patch every 3 days. TTS fentanyl was titrated to pain relief, and patients were followed up for as long as 3 months. Pain relief and the side effects of the medications were assessed daily. Twenty-six men and 27 women with a mean (+/- SD) age of 61 (+/- 12) years entered the study; 23 patients completed the full 84-day study. The mean duration of TTS fentanyl use was 58 +/- 32 days. The mean (+/- SEM) daily morphine dose during the last 2 days of stabilization was 189 (+/- 20) mg, and the mean initial fentanyl patch dose was 58 (+/- 6) micrograms/hr. The mean daily morphine dose taken "as needed" for breakthrough pain at study completion was 35 mg. The mean final fentanyl dosage at study completion was 169 (+/- 29) micrograms/hr. Pain relief was rated as good or excellent by 82% of patients during the treatment period. When asked to compare pain relief during the first month of TTS-fentanyl use to that provided by their last analgesic before study entry, 63% preferred TTS fentanyl. Side effects considered related to the fentanyl patch were nausea (13%), vomiting (8%), skin rash (8%), and drowsiness (4%). Thirty percent of patients reported adverse experiences related to the fentanyl patch, and 17% had to be discontinued from the study. We conclude that TTS fentanyl administered every 3 days for the treatment of cancer pain is effective, safe, and well tolerated by most patients.
J Pain Symptom Manage 1998 Aug
PMID:A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain. 973 1


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