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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery.
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PMID:Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia. 788 92

Nalmefene, a pure opiate antagonist structurally similar to naloxone, possesses a longer duration of action than naloxone at the same dose. However, the relative potency of these two antagonists is not known. This study was, therefore, designed to establish their potency ratio and duration of action at equipotent doses. Sixteen healthy, adult volunteers were allocated to one of four groups of four subjects each. A continuous fentanyl infusion was started to obtain a target plasma concentration of 1.5 ng/mL. The extent of respiratory depression was evaluated at 20 min (first depression) by recording end-tidal CO2 (ETCO2), respiratory rate (RR), arterial oxygen saturation (SpO2), arterial blood gases, and ventilatory response to a hypercapnic challenge. Consecutive groups then received 1, 2, 4, and 8 micrograms/kg of naloxone and nalmefene, in a double-blind, cross-over fashion, on separate occasions. Fentanyl infusion was continued and ETCO2, SpO2, and RR were recorded every 5 min until the values obtained at the first depression were reestablished (second depression). Multiple blood samples for plasma levels of the test drug and fentanyl were taken. Ventilatory function was assessed at baseline, first depression, 5 min after test drug administration, and at second depression. The ventilatory variables were compared using analysis of variance (ANOVA). There was a significant improvement in the slope and intercept of the CO2 response curve produced by the increasing doses (P < 0.05). There was no difference in recovery of these variables between the two drugs at the same dose, implying that the doses were equipotent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of potency and duration of action of nalmefene and naloxone. 810 74

We have examined the effect of isoflurane, halothane and fentanyl on heart rate variability (HRV) using power spectral analysis (PSA). Forty patients were allocated randomly to receive one of four anaesthetic techniques. Anaesthesia was induced with propofol 2 mg kg-1 and all patients breathed a mixture of 66% nitrous oxide in oxygen. Twenty of these spontaneously breathing patients received 1.5% isoflurane and 20 received 0.75% halothane. Ten patients in each of these groups received fentanyl 1 microgram kg-1 before induction. PSA was performed on 5-min segments of beat-to-beat R-R interval data taken before and 5 min after induction. No significant difference was observed in time domain or spectral HRV measures between inhalation agents. Fentanyl was associated with significantly slower heart rates, although no difference was observed in the power spectrum of those receiving fentanyl. Analysis of pooled data from the 40 subjects showed that mean heart rate was unchanged and heart rate SD was decreased, as were total and individual powers in three frequency bands of the HRV spectrum (low 0.02-0.08 Hz, mid 0.08-0.15 Hz and high 0.15-0.45 Hz). A significant decrease in the ratio of high power to (low + mid) power indicated a shift towards sympatholysis with anaesthesia. However, a significantly greater depression of mid frequency components in comparison with low or high frequencies suggests that anaesthesia selectively depressed components of the HRV mechanism, independent of a general effect on autonomic tone.
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PMID:Effect of halothane, isoflurane and fentanyl on spectral components of heart rate variability. 811 May 70

Treatment of postoperative pain is often insufficient. It normally consists of systemic application of an analgesic drug or a regional technique of analgesia. Fentanyl-TTS may be a new approach for postoperative pain therapy. Fentanyl is incorporated into a transdermal system; after application to the skin continuous release of therapeutic doses is achieved for a period of 72 h. Serum peak levels are obtained 8-16 h after application; the serum half-life is about 16-21 h because of the dermal depot. Fentanyl-TTS was administered in several clinical studies for therapy of postoperative pain. The efficacy of this new form of application could be demonstrated. For the first 12 h the patients needed supplementary doses of analgesic drugs in the same range as the placebo groups because of the lag time of fentanyl-TTS. In the following 12 h the need for supplementary analgesics was significantly reduced. After removal of the patch, the need for analgesics was still reduced for 12 h. In 21 of 341 patients respiratory depression occurred under therapy with fentanyl-TTS; no respiratory depression was observed in the placebo groups. Thus, respiratory depression might occur in up to 9% of postoperative patients treated with fentanyl-TTS. Other adverse effects were nausea (62%), vomiting (26%), sedation (22%), urinary retention (11%), headache (5%), and dizziness (8%). Local reactions under the patch were erythema (39%) or pruritus (9%). These phenomena disappeared within a few hours. The pharmacokinetics of fentanyl-TTS have two major drawbacks: during the first 12-15 h the patients need supplementary analgesics, usually opioids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fentanyl-TTS for postoperative pain therapy. A new alternative?]. 831 89

This study evaluated the safety and cognitive impact of patient-controlled analgesia with fentanyl compared to patient-controlled analgesia with morphine among elderly postoperative patients. In addition, two screening tests for cognitive impairment, the Mini Mental Status Exam and the Short Portable Mental Status Questionnaire, were compared. Ninety-six elderly patients were randomly allocated to receive patient-controlled analgesia with either fentanyl or morphine following hip or knee arthroplasty. Patients were evaluated postoperatively for clinical confusion, cognitive function test results, adequacy of analgesia, drug use and complications. Fentanyl produced less depression in postoperative cognitive function compared to morphine. The incidence of clinical confusion was not statistically different between groups (4.3% for fentanyl versus 14.3% for morphine). Fentanyl patients used more opioid based on a dose ratio of 100:1 suggesting that this dose ratio is inadequate. The incidence of urinary retention was lower in the fentanyl group. A poor agreement between the two tests of cognitive impairment mandates caution when peri-operative cognitive function is compared using different tests.
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PMID:Postoperative cognitive impairment in the elderly. Choice of patient-controlled analgesia opioid. 868 25

Continuous intravenous infusions of fentanyl, buprenorphine or nalbuphine were investigated to provide pain relief for patients after major abdominal surgery. Buprenorphine (n = 23) was given as a loading dose of 5 micrograms kg-1 and infused at 0.8 micrograms kg-1 h-1. Fentanyl (n = 20) was given as a loading dose of 2 micrograms kg-1 and infused at 0.7 micrograms kg-1 h-1. Nalbuphine (n = 21) was given as a loading dose of 200 micrograms kg-1 and infused at 80 micrograms kg-1 h-1. The infusion rate was increased when analgesia was inadequate, and decreased if respiratory depression occurred. Mean doses were respectively 0.74 +/- 0.15 microgram kg-1 h-1 buprenorphine, 0.68 +/- 0.18 microgram kg-1 h-1 fentanyl, 83 +/- 21 micrograms kg-1 h-1 nalbuphine. Titration of continuous intravenous infusion of buprenorphine and fentanyl provided better analgesia than nalbuphine with smaller doses than those reported in similar studies allowing spontaneous breathing.
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PMID:Post-operative intravenous continuous analgesia: comparison of buprenorphine, fentanyl and nalbuphine. 882 38

Several fentanyl analogs (Bagley et al., 1989, J. Med. Chem. 32, 663) were compared to fentanyl and morphine for their effects on respiratory depression as determined by arterial blood gas (pH, pCO2 and pO2) measurements. Fentanyl (0.1 mg/kg), morphine (10 mg/kg), #16 (1-phenethyl-4-[N-(pyridin-2-yl)-N-(methoxymethylcarbonyl)amino] piperidine, 1 mg/kg), #17 (1-phenethyl-4-[N-(pyridin-2-yl) -N-(2-furoyl)amino]piperidine, 0.5 mg/kg) and #29 (1-phenethyl-4-[N- (pyrimidin-2-yl)-N-(methoxy-methylcarbonyl) amino]piperidine, 10 mg/kg) produced significant respiratory depression in rats. Pretreatment with the mu1-opioid receptor selective antagonist, naloxonazine (10 mg/kg), blocked the respiratory effect of fentanyl and its analogs, but not that of morphine. The results suggest that the mu1-opioid receptor plays an important role in the respiratory effects of fentanyl and its analogs. Hence, the mechanism of fentanyl-induced respiratory depression appears to be distinct from that produced by morphine. The most likely explanation for this difference is the possible contribution of muscle rigidity and catalepsy to the observed changes in blood gas parameters caused by the fentanyl analogs, while the respiratory depression of morphine, measured by these same parameters, appears to be independent of its effect on muscle rigidity.
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PMID:Evidence for mu1-opioid receptor involvement in fentanyl-mediated respiratory depression. 889 2

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

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
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PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

We synthesized poly (DL-lactic acid)-fentanyl composites and compared the duration of analgesia after the administration of a single intrathecal dose of these agents in rats. The drug was injected with an intrathecal catheter into the intrathecal space. Fentanyl composites or plain fentanyl in doses of 2.5 or 25 micrograms were administered, respectively. Animals were then tested for analgesia using the tail-flick test. The release rate of fentanyl from fentanyl composites in vitro was also evaluated. The antinociceptive effect of fentanyl composites (25 micrograms) was significantly longer than that of plain fentanyl. Administration of poly (DL-lactic acid) alone did not induce the antinociceptive effect. Four of 7 animals given plain fentanyl (25 micrograms) exhibited temporary respiratory depression, but none of the animals given fentanyl composites showed this response. In vitro experiments demonstrated a slow release of fentanyl from the fentanyl composites. We conclude that the antinociceptive effect of fentanyl can be prolonged when administered as a poly (DL-lactic acid)-fentanyl composite in the intrathecal space with decreased systemic side effects compared with the plain formulation.
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PMID:[Prolonged antinociceptive effect of poly (DL-lactic acid)-fentanyl composites after their intrathecal injection in rats]. 1008 21


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