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)

1. Fentanyl, a synthetic mciro-opioid receptor agonist, is the preferred induction and maintenance anaesthetic agent in cardiac surgery. 2. Its actions on myocardial blood flow are poorly understood. There are reports of intra-operative myocardial ischaemia. Its reported actions on cardiorespiratory control vary widely, but do involve hypertension, bradycardia and peripheral vasoconstriction. 3. Accordingly, the postulate that fentanyl would cause coronary vasoconstriction and myocardial disadvantage was examined in awake dogs with a continuous wave Doppler flow probe mounted on the circumflex coronary artery. 4. Continuous intravenous infusion of fentanyl citrate (550 ng/kg per min) raised plasma concentrations of fentanyl to 3.37 ng/mL in a linear fashion at 20 min. There was a fall in core temperature of 0.7 degrees C and, although no apparent depression of ventilation or fall in arterial or coronary sinus PO2, there was a rise in PCO2 and H+ concentration. Some dogs salivated and panted transiently. Thus, fentanyl may reset temperature regulation in low doses but, at higher doses, is associated with metabolic acidosis. 5. In sinus rhythm, the arterial pressure of the dogs fell slightly, then rose to 115% of resting control. Circumflex flow and conductance rose early, then conductance steadily declined to 83%. Heart rate fell, then rose before returning to pre-infusion levels. The early circumflex coronary vasodilator effects, but not the later vasoconstrictor effects, were reduced in dogs with paced hearts. 6. In dogs with paced hearts, a dose-effect study using 138, 275, 550 and 1100 ng/kg per min fentanyl suggested that, at low plasma concentrations of 1-2 ng/mL, vasodilatation does occur in both coronary and systemic circulations; however, at higher doses, intense coronary and systemic vasoconstriction supervenes. 7. The dose-response effect of fentanyl on arterial baroreflex control of circumflex conductance was examined during the immediate 8 s circumflex vasodilator response to a step rise in aortic pressure caused by inflation of an intra-aortic balloon. At low plasma concentrations of fentanyl, baroreflex control of circumflex conductance appears to be enhanced but, with increasing plasma concentrations of fentanyl, appears to be depressed. 8. Therefore, the effects of fentanyl are dose dependent. At low plasma concentrations, left ventricular blood flow and its baroreflex control is enhanced but, at higher concentrations, it is depressed.
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PMID:Effect of fentanyl on baroreflex control of circumflex coronary conductance. 1111 25

Fentanyl has been shown to be effective for the management of intense pain of short duration. We have recently used intravenous fentanyl for burn wound procedures because of its rapid onset, high potency, and short duration. In this report, we reviewed our experience with fentanyl in a variety of procedural burn pain settings to develop specific recommendations about its effectiveness and safety for the treatment of pain in patients with burn injuries. The medical records of patients with burn injuries who received fentanyl for wound procedures over a 2-year period were retrospectively reviewed. Patient demographics, the amount of fentanyl administered, the level of analgesia achieved, and the incidence of adverse effects were analyzed. Fifty-five patients who were 9 months to 75 years old with burn wounds (range, 1%-90% of total body surface area) received 148 doses of fentanyl for the treatment of procedural pain. An average of 8.0 +/- 7.0 microg/kg of fentanyl (range, 0.7 to 38.0 microg/kg) was required for the first wound procedure with fentanyl. No correlation between dosage of fentanyl given and either age or percentage of total body surface area burned was observed. Transient respiratory depression was observed in 17 patients (31%). No patient required intubation or additional supplemental oxygen after the conclusion of the procedure. High doses of fentanyl are required to achieve adequate analgesia during some burn wound procedures. Respiratory depression associated with fentanyl use is transient but requires adequate preparation and trained personnel. Fentanyl may be effectively integrated into the pain control strategy for patients with burn injuries.
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PMID:The efficacy and safety of fentanyl for the management of severe procedural pain in patients with burn injuries. 1119 5

Opioid modulation of breathing during postnatal development through to the adult was investigated in the rat. Respiratory frequency, tidal volume and minute volume were recorded in unanesthetized, unrestrained rat pups and adults using barometric plethysmography. Subjects were administered the highly selective mu opioid agonists dermorphin and fentanyl. Fentanyl, which readily crosses the blood-brain barrier, was included to ensure that developmental changes in blood-brain barrier restrictions did not mask some of the dermorphin effects in older neonates. Drugs were administered subcutaneously in neonates and adults, although dermorphin was given by intracerebroventricular route only in adults. In neonates, mu agonist administration caused a gasping-like pattern of breathing, characterized by a marked fall in frequency and a smaller increase in tidal volume. The gasping response was prevented by pre-treatment with the long-acting mu1 antagonist naloxonazine (NALZ). In the presence of NALZ, mu agonists elicited only a small, but significant, reduction in tidal volume. Both dermorphin and fentanyl showed more potent activity in younger pups than in older pups, possibly in the case of dermorphin because of developmental maturation of blood-brain barrier function. In adults, fentanyl and dermorphin both caused a reduction in frequency and minute volume. The response of adults to fentanyl, but not dermorphin, was prevented by NALZ. These results suggest that both mu1 and mu2 receptors contribute to opioid-induced respiratory depression during neonatal and adult life.
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PMID:Modulation of breathing by mu1 and mu2 opioid receptor stimulation in neonatal and adult rats. 1150 87

Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.
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PMID:Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports. 1158 60

The role of duration of action on the relative reinforcing effects of three opioid drugs (fentanyl, alfentanil, and remifentanil) was evaluated. Duration and onset of action were determined using measures of respiratory depression and antinociception after i.v. administration. Effects on minute volume of respiration indicated that each of the three opioids had immediate onsets of action after i.v. administration. Fentanyl's duration of suppression of respiration and antinociception was longer than that of alfentanil, which was longer than that of remifentanil. Reinforcing strength was measured in i.v. self-administration studies in which the fixed ratio resulting in drug administration was increased from one session to the next. Comparisons were made of the behavioral economic variables P(max) and area under the demand curve (O(max)). Remifentanil maintained higher rates of responding than did alfentanil, and alfentanil maintained higher rates of responding than did fentanyl. When normalized demand functions were compared, however, the drugs did not differ significantly from each other in terms of P(max) or O(max). These data agree with those of others who have suggested that duration of action is not an important contributor to drugs' reinforcing strength.
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PMID:Relative reinforcing effects of three opioids with different durations of action. 1196 Oct 75

Epidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co-administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl- or morphine-induced antinociception in an acute pain model in rats. In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2h after treatment. Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine-induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.
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PMID:Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats. 1260 Jul 93

Mu-opioid receptor agonists depress tidal volume, decrease chest wall compliance, and increase upper airway resistance. In this study, potential neuronal sites and mechanisms responsible for the disturbances were investigated, dose-response relationships were established, and it was determined whether general anesthesia plays a role. Effects of micro-opioid agonists on membrane properties and discharges of respiratory bulbospinal, vagal, and propriobulbar neurons and phrenic nerve activity were measured in pentobarbital-anesthetized and unanesthetized decerebrate cats. In all types of respiratory neurons tested, threshold intravenous doses of the micro-opioid agonist fentanyl slowed discharge frequency and prolonged duration without altering peak discharge intensity. Larger doses postsynaptically depressed discharges of inspiratory bulbospinal and inspiratory propriobulbar neurons that might account for depression of tidal volume. Iontophoresis of the micro-opioid agonist DAMGO also depressed the intensity of inspiratory bulbospinal neuron discharges. Fentanyl given intravenously prolonged discharges leading to tonic firing of bulbospinal expiratory neurons in association with reduced hyperpolarizing synaptic drive potentials, perhaps explaining decreased inspiratory phase chest wall compliance. Lowest effective doses of fentanyl had similar effects on vagal postinspiratory (laryngeal adductor) motoneurons, whereas in vagal laryngeal abductor and pharyngeal constrictor motoneurons, depression of depolarizing synaptic drive potentials led to sparse, very-low-frequency discharges. Such effects on three types of vagal motoneurons might explain tonic vocal fold closure and pharyngeal obstruction of airflow. Measurements of membrane potential and input resistance suggest the effects on bulbospinal Aug-E neurons and vagal motoneurons are mediated presynaptically. Opioid effects on the respiratory neurons were similar in anesthetized and decerebrate preparations.
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PMID:Mu-opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbances. 1461 98

In <25 years, intrathecal administration of opioids (i.e. spinal analgesia) has evolved from an experimental model into an important therapy for obstetric analgesia and anaesthesia. A small dose of opioid delivered into the CSF provides almost immediate relief from labour pain with minimal risks to the mother and fetus. Careful attention, and prompt treatment when needed, can ameliorate the adverse effects of fetal bradycardia, respiratory depression and pruritus. The major limitation of intrathecal opioids for labour analgesia is the short duration of effect: 90-180 minutes under ideal circumstances. To address this problem, and to increase flexibility for anaesthesia as well as analgesia, the combined spinal-epidural (CSE) technique was developed. The CSE technique involves injection of drugs into the CSF and placement of an epidural catheter. An intrathecally administered opioid provides a rapid onset of labour analgesia without motor block or significant haemodynamic perturbation. The epidural catheter allows ongoing administration of medications to maintain labour analgesia and provides a means of delivering anaesthesia for operative delivery. This review will focus on intrathecally administered opioids as used as part of CSE analgesia. Considerable research has focused on the optimum dose of opioids when delivered intrathecally, with or without adjuncts, in the CSE technique. Fentanyl and sufentanil, two of the lipophilic synthetic opioids, have emerged as the most useful. Bupivacaine, a long-acting local anaesthetic, is often added to prolong the duration of analgesia, although this tends to increase the likelihood of motor blockade of the lower extremities. Comparisons of the CSE technique with standard epidural practices have shown that both are effective means of providing analgesia during labour. Controversy revolves around the incidence of fetal bradycardia following CSE and whether this phenomenon increases the rate of operative deliveries. The rapid onset of analgesia with intrathecally administered opioids must be balanced against the added risks of dural puncture and considered in the context of the whole duration of labour. Ultimately, the decision to choose a CSE technique depends on the experience of the anaesthesia provider and the local availability of drugs, equipment and monitoring capabilities.
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PMID:Intrathecal opioids for combined spinal-epidural analgesia during labour. 1296 28

In adult pentobarbital-anesthetized and unanesthetized decerebrate cats, the D(1)R agonists (6-chloro-APB, SKF-38393, dihydrexidine) given intravenously restored phrenic nerve and vagus nerve respiratory discharges and firing of bulbar post-inspiratory neurons after the discharges were abolished by the micro-opioid receptor agonist fentanyl given intravenously. Reversal of opioid-mediated discharge depression was prevented by the D(1)R antagonist SCH23390. Iontophoresis of the micro-opioid receptor agonist DAMGO depressed firing of medullary bulbospinal inspiratory neurons. Co-iontophoresis of SKF-38393 did not restore firing and had no effect on bulbospinal inspiratory neuron discharges when applied alone. The D(1)R agonists given intravenously prolonged and intensified phrenic nerve and bulbospinal inspiratory neuron discharges. They also increased reactivity to CO(2) by lowering the phrenic nerve apnea threshold and shifting the phrenic nerve-CO(2) response curve to lower et(CO(2)) levels. Intravenous fentanyl on the other hand decreased CO(2) reactivity by shifting the phrenic nerve apnea threshold and the response curve to higher et(CO(2)) levels. Fentanyl effects on reactivity were partially reversed by D(1)R agonists.
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PMID:Dopamine1 receptor agonists reverse opioid respiratory network depression, increase CO2 reactivity. 1512 91

Fentanyl, a surgical analgesic and general anaesthetic, is a lipophilic short-acting synthetic opioid, having a selective potent effect on mu receptors. The transdermal therapeutic fentanyl-system (TTS-F) allows for a continued and sustained titratable amount of fentanyl to be delivered without the inconvenience of the typical 24-h administration of other analgesics. Although incidences of respiratory depression led to TTS-F being contraindicated for postoperative analgesia, it is currently undergoing Phase III trials for nociceptive, neuropathic and chronic moderate to severe pain in a variety of settings. It demonstrates a slow pharmacokinetic profile and incidences of breakthrough pain may still require rapid analgesia, for which intravenous and bolus administration of rapid acting opioids remain 'gold standard' However, TTS-F is finding uses for chronic pain of cancer origin where it offers a solution for step 3-pain (WHO) management on the WHO analgesic ladder. More recent data indicates that TTS-F is not only effective for neuropathic but also nociceptive non-cancer and cancer pain alike. This review presents an overview of the synthesis, delivery, pharmacokinetics, toxicity and clinical pharmacology of the transdermal delivery of fentanyl.
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PMID:Transdermal therapeutic fentanyl-system (TTS-F). 1552 5


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