Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fentanyl”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

Fentanyl-related deaths: demographics, circumstances, and toxicology of 112 cases.

Since 1979, the potent narcotic analgesic fentanyl and its analogs have been synthesized in clandestine laboratories and sold as heroin substitutes. At least 112 overdose deaths have been associated with their use. In this study, toxicology data, autopsy findings, and coroners' investigative reports were reviewed in order to construct a profile of the typical fentanyl overdose victim and to identify any factors that might heighten the risk of death from fentanyl use. The "typical" fentanyl overdose victim was 32.5 +/- 6.7 years of age (range, 19 to 57 years), male (78%, compared with 22% female), and Caucasian (50%, compared with 29% Hispanic, 20% Black, and 0.9% Asian). With the exception of his or her age, the typical fentanyl overdose victim is quite similar to the typical heroin user. Nearly all the deaths (94%) occurred in California, yet within the state they were widely distributed throughout 17 counties and 44 cities. Pulmonary edema and congestion and needle puncture sites were consistent postmortem findings. No preexisting medical conditions were identified as possible risk factors. Although most of the fentanyl victims had a prior history of intravenous drug use, morphine or codeine were not commonly found, which suggests that the victims had little or no opiate tolerance. Ethanol was present in 38% of the cases and is thought to be a significant risk factor. Mean fentanyl concentrations in the body fluids were quite low: 3.0 +/- 3.1 ng/mL (0.3 +/- 0.31 micrograms/dL) in blood and 3.9 +/- 4.3 ng/mL (0.39 +/- 0.43 micrograms/dL) in urine, measured by radioimmunoassay. Although the potency of the analogs and the purity of street samples varies considerably, it is probably the general availability of the drug rather than the potency of a particular analog that determines the incidence of overdose deaths.

Adult↗

Central action of narcotic analgesics. Part III. The role of endogenous noradrenaline in hyperactivity induced by morphine or fentanyl in mice.

Hyperactivity produced in mice with morphine or fentanyl, and methylamphetamine was antagonized by naloxone. The depression of locomotor activity induced by codeine was practically unchanged by the opiate antagonist. L-DOPA did not restore the stimulatory action of morphine and fentanyl in reserpinized mice. The hyperactivity produced by morphine and fentanyl was abolished in mice treated with alpha-methyl-p-tyrosine, but this was restored by L-DOPA administration. Agents inhibiting the central noradrenaline receptors, phentolamine, phenoxybenzamine, and aceperone, prevented or even reversed the locomotor stimulatory action of morphine and fentanyl. Pimozide did not affect the increase of locomotor activity produced by morphine, but depressed that induced by fentanyl. Haloperidol, used in a dose which did not affect the locomotor activity of mice, completely blocked or even reversed the stimulatory action of morphine and fentanyl, and potentiated the depression of locomotor activity produced by pentazocine and codeine. Diethyldithiocarbamate significantly depressed, but did not inhibit completely the stimulatory action of morphine and fetanyl. The stimulatory action of methylamphetamine was also significantly depressed. It seems that the stimulatory effect of morphine and fentanyl depends on the release of endogenous noradrenaline.

Animals↗

[Determination of the basic data on fentanyl dosage in neuroleptanalgesia for heart surgery].

The use of high-dose fentanyl (50-150 micrograms/kg) in anaesthesia for cardiac surgery includes the need of prolonged ventilatory support in the postoperative period. Therefore, the possibility of choosing a useful dosage regimen of smaller doses of fentanyl (up to 20 micrograms/kg) leading to analgesic serum levels of greater than 3 ng/ml is investigated in this study. Fentanyl was determined by radioimmunoassay in 20 patients during and after typical cardiosurgical operations. Three bolus injections of 7 micrograms/kg were applied in the first group (n = 8). Analgesic fentanyl concentrations were reached 12-24 minutes after the first injections. The characteristic pharmacokinetic influences - especially the enlarged volume of distribution and the prolonged elimination time - were visible following repetitive doses during extracorporeal circulation. Based on these results the injection mode was changed in the second investigation group (n = 6) - 2/3 of the total dose before the start of extracorporeal circulation - resulting in analgesic fentanyl concentrations for the whole course of the operation. More stable serum levels were obtained with the combination of primary bolus injection followed by continuous infusion (3rd group, n = 6), but a higher fentanyl amount and prolonged postoperative ventilation times were registered in this group. Bolus injections adapted to the special pharmacokinetic situation seem to be the best variant for the desired effect of producing sufficient analgesic levels without long-lasting ventilatory depression with a limited total dose of fentanyl.

Adult↗

Antagonism of fentanyl-induced respiratory depression with nalmefene.

We determined the ability of a new opioid antagonist, naimefene, to prevent fentanyl-induced respiratory depression in 8 healthy male volunteers. Ventilation and pulmonary function were measured with the respiratory inductive plethysmograph (RIP), which is non-invasive and requires no connection to the airway. Each volunteer was tested two times on different days. During the first session, each volunteer was monitored for one hour of baseline measurement followed by 4 hourly injections of fentanyl (1 microgram/kg) administered in an open-label manner. In the second session, the subjects were monitored for one hour after 1 mg of intravenous nalmefene was administered. Intravenous fentanyl or identical placebo were then given in a double-blind manner as in the first session. Progressive and profound respiratory depression occurred with fentanyl administration alone. In the absence of nalmefene, fentanyl converted normal breathing pattern to an irregular breathing pattern. When the subjects were treated with nalmefene prior to fentanyl administration, all of these changes were almost completely prevented. Pulmonary variables which reflected this difference between the fentanyl-alone group and the nalmefene-pretreated groups included frequency (p less than 0.001), tidal volume (p less than 0.001), percent rib cage contribution to tidal volume (p less than 0.001) and expiratory time (p less than 0.001). This study showed that nalmefene is an effective long-acting opioid antagonist, and that RIP accurately measures changes in respiration caused by opioid administration.

Adult↗

Antinociceptive activity of pentamorphone, a 14-beta-aminomorphinone derivative, compared to fentanyl and morphine.

The analgesic potency of pentamorphone, a 14-beta-aminomorphinone derivative, was compared to that of fentanyl and morphine by examining quantal dose-effect curves generated from data obtained in the mouse hot plate, rabbit tooth-pulp, and dog tail clamp tests. Onset and duration of antinociceptive effects were also compared. The ED50 values (mg/kg) were determined in mice for pentamorphone (0.0039), fentanyl (0.016), and morphine (7.3). In the rabbit tooth pulp test the ED50 values were 0.0009 mg/kg for pentamorphone, 0.0074 mg/kg for fentanyl, and 1.1 mg/kg for morphine; in the dog tail clamp test these values were 0.012 mg/kg for pentamorphone and 0.018 mg/kg for fentanyl. Duration of action (defined as the time until response to tooth pulp stimulation declined to 50% of maximum possible effect [MPE]) was 10 min with twice the IV ED50 for pentamorphone in mice. This duration was similar to that of the equipotent dose of fentanyl but much shorter than the duration of an equipotent potent dose of morphine (60 min). The duration in rabbits of the ED98 (IV) dose of pentamorphone was 65 min compared to 35 min for an equipotent dose of fentanyl and 200 min for morphine. Intramuscular doses of pentamorphone had significantly faster onset and shorter duration times than equipotent doses of morphine in both mice and rabbits. Pretreatment with naloxone in mice and rabbits attenuated the development of the antinociceptive effects of pentamorphone. This study shows that pentamorphone is a potent analgesic with a duration of action similar to that of fentanyl.

Analgesics↗

Antagonism of the respiratory and analgesic effect of fentanyl produced by aminophylline.

Low-dose aminophylline may reverse the respiratory depression caused by morphine and fentanyl. High-dose aminophylline may decrease an animal's tolerance to painful stimulation. We postulated that fentanyl combined with low-dose aminophylline could result in adequate analgesia without the side-effect of respiratory depression. Twelve healthy volunteers were randomly divided into group A and group B each consisting of six persons. Group A received fentanyl 3 ug/kg and group B received fentanyl 3 ug/kg plus aminophylline 3 mg/kg iv. Arterial carbon dioxide tension (PaCO2) was taken as an index of respiratory status and the analgesic effect of fentanyl was estimated by measuring changes in maximum pain tolerance (MPT) using a pressure clamp device. The results showed that 3 mg/kg of aminophylline significantly alleviated the respiratory depression effect of fentanyl 15 and 25 min post-injection (P less than 0.05), without attenuation of its analgesic effect. The severe hemodynamic disturbance and acute reversal of analgesia, which may be induced by naloxone, were not observed. Our results suggest that aminophylline safely reverses the respiratory depression caused by fentanyl.

Adult↗

[The effect of atropine, fentanyl and alfentanyl on cardiocirculatory parameters and thoracic rigidity in the induction phase of intubation anesthesia].

Fentanyl and alfentanil may cause bradycardia if used in combination with succinylcholine during induction of anaesthesia. We therefore studied the influence of atropine, fentanyl and alfentanil on the haemodynamics of 90 urological patients (ASA I, II), who were allocated at random to six groups containing 15 patients each. Induction of anaesthesia was carried out using atropine 0.01 mg/kg-1, fentanyl 0.15 mg or alfentanil 1.5 mg depending on the assigned group: I atropine + fentanyl, II: atropine + alfentanil, III: fentanyl, IV: alfentanil, V: control (no atropine, no analgetic), VI: atropine. Following 2 mg alcuronium and thiopentone 4 mg/kg-1 intubation was performed with 2 mg/kg-1 succinylcholine. Atropine in combination with fentanyl caused a significant increase in heart rate following endotracheal intubation (p less than 0.05). Arrhythmias occurred in the groups with atropine in 4 out of 45 cases, while a chest wall rigidity was not influenced by atropine. Bradycardia occurred after fentanyl or alfentanil with atropine in the same frequency as without atropine. According to our results the routine use of atropine for induction of anaesthesia with thiopentone/fentanyl or alfentanil even in combination with succinylcholine is not required in ASA I or II patients.

Adult↗

Diazepam enhances fentanyl and diminishes meperidine antinociception.

A rabbit tooth pulp antinociceptive model was used to investigate the effect of prior administration of diazepam or muscimol on the potency and duration of fentanyl and meperidine Potency experiments compared ED(50) values in all-or-none dose-response assays between both muscimol (0.25 mg/kg) and saline, and diazepam (1.5 mg/kg) and propylene glycol vehicle. An all-or-none effect was defined as doubling of voltage threshold to elicit a lick/chew evoked response. Duration experiments compared time (minutes) to 50% maximum possible effect (MPE) of an ED(90) dose of fentanyl (0.04 mg/kg) and to 50% and 20% MPE of an ED(98) dose of meperidine (17 mg/kg) 10 minutes after pretreatment with diazepam (1.5 mg/kg). Prior (10 minutes) injection of diazepam (1.5 mg/kg) increased the ED(50) value for meperidine (3.06 mg/kg) compared with its control (1.48 mg/kg), indicating a decrease in antinociceptive potency. The same dose of diazepam decreased the ED(50) value for fentanyl (1.1 μg/kg) compared with its control (13.1 μg/kg), indicating an increase in antinociceptive potency. Muscimol also had a similar effect on fentanyl (ED(50), 1.8 μg/kg) compared with saline control (ED(50), 13.8 μg/kg). Diazepam, vehicle, and muscimol by themselves had no effect on voltage thresholds to elicit a lick/chew response. Time to 50% MPE for diazepam-fentanyl was 38 minutes vs. 25 minutes for vehicle-fetanyl; time to 20% MPE for diazepam-meperidine was 38 minutes vs. 54 minutes for vehicle-meperidine (maximum percentage of MPE produced by diazepam-meperidine was 40% compared with 100% MPE for vehicle-meperidine). Percentages of MPE for diazepam-meperidine were significantly lower than those for vehicle-meperidine at all time intervals, whereas percentages of MPE for diazepam-fentanyl were significantly greater than those for vehicle-fentanyl over time.

Animals↗

[Disposition of fentanyl in human blood].

Plasma protein binding and uptake of fentanyl by erythrocytes was studied in a group of 30 healthy patients of both sexes (aged 4-84 years), undergoing orthopaedic or minor surgical operations. Using equilibrium dialysis (24 h, 37 degrees C, phosphate buffer pH 7.4 containing fentanyl 5 ng/ml) the protein bound fraction was found to be 72.4% +/- 7.9 (mean +/- standard deviation). Proteins in the plasma of children or elderly patients bound to a slightly higher degree as compared with the group of medium age, while no differences between sexes were observed. The addition of various intravenous anaesthetic drugs in a therapeutic concentration range did not alter plasma protein binding seriously. There seems to be a correlation between fentanyl plasma protein binding and the plasma content of acid alpha-1-glycoproteins. Human erythrocytes were found to equilibrate very rapidly with plasma fentanyl, the partition coefficient being almost unity. Distribution into the red cells was not influenced by adding intravenous anaesthetics or plasma expanders to the blood samples, nor was it altered by changes of pH or temperature. Storage of fentanyl did not modify erythrocyte morphology even at high concentrations, as indicated by normal MCV or MCHC. Fentanyl was found not to be metabolized in human whole blood, haemolysate or plasma. The activity of serum enzymes commonly used in routine diagnosis was not influenced by fentanyl concentrations in a range up to 1,000 ng/ml.

Adolescent↗

The effect of fentanyl on arginine vasopressin and cortisol secretion during anesthesia.

The effects of nitrous oxide-oxygen plus small doses of fentanyl with (N = 7) and without (N = 15) naloxone and the effects of nitrous oxide-oxygen plus halothane (N = 13) on plasma concentration of arginine vasopressin (AVP) and cortisol were studied in normal patients before and during gynecologic laparotomies. Patients given fentanyl alone received incremental doses of 0.002 mg/kg before, during, and after induction of anesthesia. Naloxone, when given, was injected in doses of 0.005 mg/kg before administration of fentanyl. In the fentanyl group, the induction of anesthesia resulted in a significant increase in the plasma AVP levels and a significant decrease in cortisol levels. In contrast, while the halothane group also showed a decrease in plasma cortisol level, there was no change in the AVP levels. There were comparable increases in AVP and cortisol levels in both groups during surgery. Administration of naloxone before fentanyl prevented the increase of plasma AVP levels during anesthesia and surgery and blunted the elevation of plasma cortisol during surgery. Our results suggest that the increase in plasma AVP levels after induction of fentanyl anesthesia may not be induced by the stress of intubation and that small doses of fentanyl may cause AVP release during anesthesia.

Adult↗

Absence of seizures during induction of anesthesia with high-dose fentanyl.

Anesthesia was induced in six patients scheduled for elective aortocoronary bypass (ACB) surgery with intravenous fentanyl, either 50 (n = 2) or 150 micrograms/kg (n = 4) over 20 or 60 sec, respectively. Patients had been given their usual antianginal medications before surgery and were premedicated with morphine sulfate. Arterial plasma fentanyl levels were measured repetitively at frequent intervals, and eight leads of the cortical electroencephalogram (EEG) were recorded continuously. Peak plasma fentanyl concentrations exceeded 1750 ng/ml at the end of the injection of 150 micrograms/kg and then decreased by more than 75% within 3 min. In an additional two patients, incremental doses of fentanyl (25, 25, 50, 50 micrograms/kg; total 150 micrograms/Kg) maintained fentanyl concentrations between 30 and 650 ng/ml for the entire 15 min of the study. In all cases, diffuse slow-wave EEG activity, characteristic of fentanyl anesthesia, was seen. Motor activity, including wrist flexion and ocular movements, was observed during the onset of fentanyl-induced truncal rigidity, but no seizure-like activity was found in the EEG.

Aged↗

Identification and quantitative determination of fentanyl metabolites in patients by gas chromatography--mass spectrometry.

Although fentanyl has been used widely as a short-acting narcotic analgesic, its metabolism in humans has not been clarified. In this study, three fentanyl metabolites were identified in the urine of eight surgical patients receiving 0.3-0.5 mg of fentanyl intravenously. The metabolites 4-N-(N-propionylanilino)piperidine, 4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine, and unchanged fentanyl were identified by GC-mass spectrometry in urine collected 6 h after administration. Fentanyl and its main metabolite, 4-N-(N-propionylanilino)piperidine, were determined quantitatively in the urine of five additional patients receiving 0.5 mg fentanyl intravenously. Urinary excretion of fentanyl and 4-N-(N-propionylanilino)-piperidine during the first 12 h after injection accounted for 0.3-4.0% and 26 to 55% of the dose, respectively.

Adult↗

[Biotransformation of fentanyl. III. Effect of chronic drug exposure on the distribution, metabolism and excretion in the rat].

In male Wistar rats, tissue distribution and excretion of fentanyl and its metabolites were studied after intravenous of intramuscular injection. Oxidative desalkylation leading to phenylacetic acid and norfentanyl proved to be the main degradation pathway in-vivo, whereas other metabolites, including the pharmacologically still active p-hydroxy(phenethyl)fentanyl were formed only in minor quantities. All compounds could be detected in any tissue under study (brain, lung, liver, kidney, muscle and fat) as well as in the gastric contents, the amount of fentanyl in the latter cumulating to about 2% of the total dose 60 min after injection, compared with about 10% in the fat. In rats chronically treated with ethanol, nicotine, morphine, phenobarbital, promethazine or diazepam, major differences in in-vitro fentanyl metabolism by liver homogenates were observed including both inhibition and induction. Phenobarbital pretreatment also induced extrahepatic biotransformation in kidney, adrenals and intestinal mucosa. On the other hand, tissue concentrations of fentanyl and its metabolites did not clearly reflect the in-vitro changes in metabolic activity. Fentanyl brain levels were found to be lower in the treatment groups but seemed not to correlate with pharmacodynamics, less effects following injection being observed only after ethanol and morphine. The in-vitro metabolic drug interaction proved to be of less importance than changes in diuresis and/or urinary pH when excretion products were analysed. As a conclusion, it is suggested that altered sensitivity of brain tissue rather than changes in bioavailability must explain variations in dose-response relationship which are frequently believed to be seen when fentanyl is used in patients with chronic drug administration.

Animals↗

[Epidural fentanyl analgesia for the relief of postoperative pain (author's transl)].

The results are reviewed which were obtained with epidural administration of fentanyl for the relief of pain in 134 patients who had undergone abdominal surgery or had sustained multiple fractures of the ribs. Single doses of 0.1 mg of fentanyl were given epidurally via an indwelling catheter inserted between L1/L2 or L2/L3 or, in the case of 7 patients with multiple rib fractures, between Th8/Th9. The results were satisfactory to excellent. An increase in the volume of the fentanyl solution from 10 ml to 20 ml increased the number of patients who were free from pain from 61 per cent to 81 per cent. The analgesic effects of individual doses lasted 2-8 hours (average 5.5 h). Persons with multiple rib fractures needed further injections on average every 3.5 hours. In these cases epidural fentanyl administration also proved valuable in combination with artificial ventilation. There were no serious side-effects. A comparison of the clinical efficacy of fentanyl proved that the same doses of the drug were more effective if given epidurally than if injected intramuscularly. The serum concentrations of fentanyl showed considerable individual variations after both intramuscular and epidural administration with peak values varying correspondingly. Epidural injections caused a steeper rise in concentration than did intramuscular administration. Although none of the patients developed respiratory depression the possibility of respiratory failure should be taken into account when employing epidural fentanyl analgesia. The method is very effective in intensive therapy for relieving postoperative or post-traumatic pain, but is unsuitable for the relief of chronic pain because the analgesic effect is comparatively short-lived.

Adult↗

[Biotransformation of fentanyl. II. Acute drug interactions in rats and men (author's transl)].

Rat tissue homogenates were used to study fentanyl biotransformation. The liver was shown to be the most important metabolizing organ, whereas extrahepatic metabolism occurred only to a minor degree in the kidneys. The products of oxidative desalkylation, phenylacetic acid and norfentanyl, could be identified as well as small amounts of p-hydroxy-(phenethyl)fentanyl, which is pharmacologically still active. Major sex differences were observed, male rats showing nearly twice as much activity as female animals. Several anaesthetic agents, often used in combination with fentanyl, were tested with respect to their influence on fentanyl metabolism. Most of them caused an inhibition of biotransformation and/or variations in product distribution, when they were added to in-vitro incubations or given to the animals prior to enzyme preparation. This experimental design proved to be useful as a screening method to predict metabolic drug interactions. Halothane and enflurane, which are strong inhibitors in rats, were demonstrated to delay fentanyl metabolism in man, too. Fentanyl plasma levels under halothane anaesthesia were found to be more than twice as high as during neuroleptanaesthesia. The importance of other agents, e.g. ketamine, promethazine or local anaesthetics, remains to be examined. Variations of biotransformation reactions among patients as well as the reported drug interactions might explain some differences in fentanyl blood concentrations reported in the past, but must also be taken into account when intensity and duration of effects or side-effects are discussed.

Adult↗

[Comparison between the analgesic effects of fentanyl and morphine in conscious man (author's transl)].

Fentanyl citrate is administered intramuscularly at increasing doses to patients suffering from an intense pain in the facial or trigeminal nerves territory. Fentanyl induces a very intense analgesia which develops during the hour following the administration. The intensity and the duration of the effect are dose related. Compared to that of morphine chlorhydrate, in the same conditions, the analgesia induced by fentanyl citrate is much less intense than expected: fentanyl seems to be only 25 times more potent than morphine. Furthermore, the observed duration of action of fentanyl makes it impossible to be still classified with the short time acting analgesics: with equianalgesic doses, morphine and fentanyl have the same time of initiation and the same duration of action. As observed, the time of the clinically useful analgesia is longer than 3 hours after injection of 0.006 mg/kg of fentanyl or of 0.150 mg/kg of morphine.

Female↗

The effect of pre-emptive fentanyl on formalin pain in mice.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine if pre-emptive systemic fentanyl administration would decrease the amount of formalin pain in mice. METHODS: Under halothane anesthesia, formalin was injected in the hindpaw of mice. The animals were randomly assigned to receive no systemic fentanyl (group 1; n = 20); subcutaneous fentanyl, 50 micrograms/kg 5 minutes prior to formalin injection (group 2; n = 20); or subcutaneous fentanyl, 50 micrograms/kg 5 minutes after formalin injection (group 3; n = 20). After recovery from anesthesia, the formalin-induced paw-licking response was observed for 1 hour. The time to first paw lick, the number of paw licks, and the duration of paw licking were compared among the groups with an analysis of variance. RESULTS: The fentanyl-treated mice in groups 2 and 3 had a significantly longer time to first paw lick, had a lower number of paw licks, and had a shorter duration of paw licking compared to the control mice in group 1. There was no significant difference in formalin pain behavior between the mice receiving fentanyl before or after formalin injection. CONCLUSIONS: Pre-emptive administration of subcutaneous fentanyl does not decrease the severity of acute pain in mice.

Analgesics, Opioid↗

An enzyme-linked immunosorbent assay for urinary screening of fentanyl citrate abuse.

An enzyme-linked immunosorbent assay (ELISA) for quantitation of urinary fentanyl was evaluated as a screening tool for detecting abuse of this potent narcotic. The assay was found to have reproducible calibration curves from 0.5 to 10 ng/mL and a limit of detection of 0.5 ng/mL. Interference by proteins, glucose, or pH was negligible. The assay was specific for fentanyl with little cross-reactivity against despropionyl fentanyl and norfentanyl metabolites, other analgesics and common drugs of abuse. To evaluate its use in humans, urines were collected from 57 normal individuals, 48 patients seen in the Emergency Department, and 18 surgical patients receiving either low (50 micrograms) or moderate fentanyl dosage (200 and 250 micrograms) for routine anesthesia. In patients receiving 50 micrograms (a dose consistent with early abuse), urinary fentanyl was detectable for 3 to 10 h post administration. In patients receiving 200 or 250 micrograms (a dose more consistent with addiction), urinary fentanyl was detectable for longer time periods (> 24 h). These results indicate that the ELISA is sensitive for the detection of recent fentanyl exposure under conditions likely to mimic those in abuse and addiction. The assay is simple to perform, reliable, and can be used to screen urine specimens prior to gas chromatography/mass spectrometry (GC/MS) confirmation.

Calibration↗