Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fentanyl is a synthetic narcotic which, when administered intravenously, has a rapid onset and short duration of action. It produces less cardiovascular depression than either meperidine or morphine. Experience with 100 examinations performed using intravenous fentanyl and diazepam for analgesia and sedation in adults is reviewed. There were no complications, and effective analgesia was obtained in all cases. Fentanyl has distinct pharmacologic advantages over both morphine and meperidine for use in radiologic special procedures.
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PMID:Fentanyl and diazepam for analgesia and sedation during radiologic special procedures. 378 61

Fentanyl, a short-term analgesic frequently used in neuroleptanalgesia, has in a number of cases been reported to cause unexpected, severe postanesthetic respiratory depression which can successfully be treated with naloxone. Several explanations for this rebound effect produced by fentanyl (in combination with other drugs) have been proposed, though so far none has proved completely satisfactory. The possibility that this effect may be due to a secondary accumulation of fentanyl or fentanyl metabolites with opioid activity in the brain has led us to investigate the relative opioid potency of several known or proposed metabolites by measuring their inhibitory action on the contraction of guinea-pig ileum in comparison with that of morphine, pethidine, and fentanyl itself. Two proposed metabolites containing the phenethyl sidechain were found to possess an opioid activity lying between that of morphine and pethidine, whereas metabolites without the side-chain were generally less active than pethidine. Using thin-layer chromatography, it was possible to detect one of these proposed active metabolites in vivo in rats. This result may have some relevance for the understanding of the fentanyl rebound. However, the possibility that multiple doses of fentanyl, such as may be given during neuroleptanalgesia, or interactions with other drugs, e.g. tranquilizers and general anesthetics, may be the cause of fentanyl rebound, remains open.
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PMID:Opioid activity and distribution of fentanyl metabolites. 380 83

Fentanyl and alfentanil produce very similar electroencephalographic (EEG) changes in humans. With increasing serum concentrations of either narcotic, progressive slowing in frequency occurs. This narcotic effect on the brain was quantitated using off-line EEG power spectrum analysis. During EEG recording, six unpremedicated patients received a fentanyl infusion (150 micrograms/min), and six received alfentanil (1,500 micrograms/min) until a specific level of EEG depression (delta waves) occurred. Timed arterial blood samples were obtained for measurement of the narcotic serum concentrations. The narcotic-induced EEG changes were found to lag behind (in time) the serum narcotic concentration changes. To accurately relate EEG changes to serum narcotic concentrations, a pharmacodynamic model (inhibitory sigmoid Emax) was combined with a pharmacokinetic model that incorporated an "effect" compartment. (The effect compartment is the separate pharmacokinetic compartment where drug effect is directly proportional to drug concentration. It is the effect site.) The magnitude of the time lag was quantitated by the half-time of equilibration between serum narcotic concentrations and concentrations in the effect compartment. With fentanyl a significantly greater time lag was present (half-time = 6.4 +/- 1.3 min; mean +/- SD) than with alfentanil (half-time = 1.1 +/- 0.3 min). This difference in time lag between blood concentration and effect may be due to the larger brain-blood partition coefficient for fentanyl. The steady-state serum concentration that caused one-half of the maximal EEG slowing was 6.9 +/- 1.5 ng/ml for fentanyl, compared with 520 +/- 163 ng/ml for alfentanil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. 391 13

Ten patients for coronary vein grafting had induction of anesthesia with fentanyl (30 micrograms/kg), followed by enflurane-oxygen sufficient to decrease systolic blood pressure by 27% before intubation. Enflurane was continued in concentrations to maintain blood pressure below that with patients awake. All patients had preserved ventricular function and effective beta-blockade. Studies of hemodynamic functions and myocardial blood flow and oxygenation were done before induction, six times during anesthesia, and twice postoperatively. The blood pressure decrease on induction and before bypass was due to reduced cardiac index without decreased heart rate or systemic resistance. Stroke work index decreased 47% on induction and remained below awake level throughout. Coronary sinus blood flow decreased 26% after intubation and remained so before bypass. Without change in coronary resistance, coronary sinus oxygen content increased 30% on induction and stayed elevated before bypass. Normal lactate extraction continued after induction and increased before bypass; mean extraction decreased after bypass, with one or two hearts producing lactate in the first 24 postoperative hr. Fentanyl-enflurane-oxygen maintained a steady mild hemodynamic depression during the operation and soon afterward, which preserved myocardial oxygenation.
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PMID:Myocardial metabolism and hemodynamic responses with fentanyl-enflurane anesthesia for coronary arterial surgery. 394 Apr 69

To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 micrograms/kg, then were administered 1, 2, 4, 6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. One hour following placebo pretreatment, the initial fentanyl dose produced marked respiratory depression. Minute ventilation and occlusion pressure at a PCO2 60 mmHg during rebreathing (VE60 and P(0.1)60) were reduced to 29 and 41% of control, respectively. The slopes of the ventilatory and occlusion pressure responses also decreased significantly to 51 and 55% of control. Respiratory effects were similar with all subsequent fentanyl doses. Pretreatment with 2 mg nalmefene completely prevented the subjective and respiratory effects of fentanyl for the entire 8 h of the experiment. Nalmefene, 1 mg, significantly blunted the fentanyl effects for the same period, but VE60 values at 6 and 8 h were depressed significantly (P less than 0.05) to 66 and 61% of control. The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time VE60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44-55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged antagonism of opioid action with intravenous nalmefene in man. 394 4

Fentanyl by continuous i.v. infusion (1.5 microgram kg-1 min-1 or 0.5 microgram kg-1 min-1) was compared with placebo infusion as an analgesic regimen for 24 h after hysterectomy. The drugs were infused using a new disposable device which required no external power source. All patients were allowed morphine i.m. if they experienced pain. Patients in the higher dose fentanyl group demanded less i.m. morphine and had better pain relief after operation, without important respiratory depression.
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PMID:Fentanyl by constant rate i.v. infusion for postoperative analgesia. 397 7

It is reported that benzodiazepines such as diazepam will stimulate the opiate receptor system and that B-carboline drugs, which are benzodiazepine antagonists, may interact with opiate receptors directly. The ability of 3-hydroxymethyl-B-carboline (3-HMC) to antagonize several parameters of fentanyl anesthesia was tested here in rats. Fentanyl (25 and 100 micrograms/kg iv) produced dose dependent depression of cerebral blood flow (CBF), measured by radioactive microspheres, and cerebral oxygen consumption (CMRO2). These effects were significantly inhibited by 10 mg/kg 3-HMC iv. To test for the specificity of this effect, 3-HMC was also given to rats ventilated with inspire concentrations of 2% halothane. Halothane depressed CMRO2 equally in 3-HMC and vehicle treated rats, indicating no significant effect of the benzodiazepine antagonist. Blood pressure was increased in 3-HMC compared to vehicle treated animals during both fentanyl and halothane anesthesia. CBF was increased in 3-HMC vs vehicle treated rats during halothane anesthesia but this could be accounted for by the elevated blood pressure and lack of cerebral autoregulation rather than a direct cerebrovascular effect. 3-HMC decreased the sleep time and respiratory depressant effects of fentanyl but enhanced the analgesic effects of the opiate, as measured by time to respond to a hot plate stimulus. These results indicate that 3-HMC has the ability to specifically antagonize fentanyl anesthesia. These effects may be produced by an action of 3-HMC at the benzodiazepine receptor and/or by an action of the B-carboline at opioid receptors.
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PMID:A benzodiazepine antagonist inhibits the cerebral metabolic and respiratory depressant effects of fentanyl. 399 26

The authors present a study of 20 cases of epidural obstetrical analgesia. A Bupivacaine-Fentanyl mixture was given by continuous flow to bring about this analgesia. After an initial injection of 10 ml (9 ml of 0.25% Bupivacaine and 0.05 mg Fentanyl), a mixture of 45 ml of 0.25% Bupivacaine and 0.25 mg Fentanyl was perfused into the epidural space using an electronic pump syringe, delivering at a rate of 5 ml/hr. The mean time of analgesia until the delivery is 4 h 40 mn and the women in labour received a mean of 31.14 ml of 0.25% Bupivacaine (77.85 mg) and 0.173 mg Fentanyl. It took only 5 1/2 minutes to set up this form of analgesia. Not a single patient had any pain the first stage of labour nor in the second stage, and 95% of them were able to push efficiently. There are no detectable changes in the haemodynamic parameters in either the mothers or the fetuses and no depression of maternal respiration was found. In each case the Apgar score was 10 after 5 minutes. In summary, the use of an electronic pump syringe to deliver a Bupivacaine-Fentanyl mixture in obstetrical labour is a great improvement in analgesia without any secondary effects in the mother and child.
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PMID:[Peridural obstetrical analgesia using an electronic syringe]. 402 54

Fentanyl, a synthetic opiate with a (clinical) potency of 50 to 100 times that of morphine, was introduced into clinical practice in the early 1960s. Usually administered by single intravenous doses, it developed a reputation for having a short duration of action and it was assumed that this was a consequence of rapid removal from the body. However, as clinical experience increased, it was realised that administration of multiple doses or large doses during narcotic-based anaesthesia sometimes led to delayed recovery and prolonged respiratory depression, suggesting that the duration of action was limited by redistribution within the body rather than removal from the body. Recent developments in analytical techniques have allowed pharmacokinetic studies and these have confirmed this opinion; fentanyl is rightly regarded as having a redistribution-limited duration of action after single or infrequent doses (analogous to thiopentone). However, the magnitude of the pharmacokinetic constants reported for fentanyl are remarkably inconsistent even in healthy volunteers, for reasons apparently only explainable by assay differences. Hence, estimates of apparent volume of distribution (area) range from around 60L to over 300L, estimates of terminal half-life range from about 1.5 to 6 hours (15 hours in geriatric patients) and total body clearance ranges from 0.4 to over 1.5 L/min. Renal excretion accounts for up to 10% of the dose; the remainder of the clearance would appear to be predominantly hepatic, but with contributions from other tissues. Continued clinical developments of narcotic-based anaesthetic techniques have resulted in high doses of narcotic being used, with oxygen, as the sole anaesthetic agents. At present these techniques are usually based on fentanyl, and the technique is frequently called 'stress-free anaesthesia' because of the effects in obtunding the 'stress response' caused by surgery (elevation of plasma concentrations of cortisol, glucose, ADH, etc. in the intra- and post-operative period) and the lack of deleterious effects on the cardiovascular system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of fentanyl and its newer derivatives. 622 71

Protecting the patient's airway is of paramount importance in the induction of general anesthesia. For the patient at risk of regurgitation of stomach contents, the rapid-sequence (crash) induction provides protection, but at the expense of increased stress response to laryngoscopy and intubation. This stress response is especially dangerous for the patient at risk for myocardial ischemia. The purpose of this study was to examine the efficacy of using low-dose fentanyl (5 micrograms/kg) to reduce cardiovascular and neuroendocrine stress responses to rapid-sequence induction. Thirty patients were randomly assigned to a rapid-sequence induction protocol either with or without fentanyl preloading. Fentanyl-preloaded patients (fentanyl group) received 2 mg/kg of thiopental whereas patients who were not preloaded with fentanyl (control group) received 4 mg/kg of thiopental. Data collected as indices of the stress response included heart rate, systolic, diastolic, and mean blood pressures, and plasma concentrations of catecholamines (epinephrine, norepinephrine, dopamine) and beta-endorphin. Electrocardiograms (modified V5 lead) were monitored for dysrhythmias and ST segment depression. Control patients had higher systolic, diastolic, and mean blood pressures after intubation than did patients given fentanyl (P less than 0.05). Although the incidence of dysrhythmias was decreased by fentanyl (20% vs 42%), this difference was not statistically significant. Plasma concentrations of beta-endorphin and norepinephrine increased significantly in control patients but not in patients given fentanyl (P less than 0.05). Low-dose fentanyl (5 micrograms/kg) reduces some aspects of the stress response to rapid-sequence induction of anesthesia.
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PMID:Fentanyl preloading for rapid-sequence induction of anesthesia. 631 5


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