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

To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fentanyl-induced ventilatory depression: effects of age. 291 58

Beta-endorphin has been implicated in the cardiovascular depression that occurs in shock. While pharmacologic doses of beta-endorphin cause hypotension, physiologic doses of beta-endorphin have not been studied. In this study, six dogs (group I) were given IV beta-endorphin (peak concentrations previously determined in canine shock, 3,200 pg/ml); 5 minutes prior to beta-endorphin infusion, four dogs (group II) were given naloxone, 2 mg/kg bolus, and continuous infusion, 2 mg/kg/hr. In group I, beta-endorphin decreased stroke volume (from 0.99 +/- .12 to 0.57 +/- .08 ml/kg), dP/dt (from 3,167 +/- 140 to 2,875 +/- 412 mmHg X sec), and coronary blood flow (from 2.5 +/- .47 to .68 +/- .11 ml/min/gm), while heart rate rose significantly. Naloxone pretreatment maintained dP/dt, stroke volume, and coronary blood flow with no change in heart rate or mean arterial pressure. This study confirms that beta-endorphin depresses contractility and coronary blood flow in normovolemic nonstressed dogs, suggesting that beta-endorphin is in part responsible for cardiovascular depression in shock.
 ...
PMID:Cardiocirculatory effects of physiological doses of beta-endorphin. 293 43

Chemical antagonists were used to assess the role of beta-endorphin and arginine-vasopressin (AVP) in canine endotoxin shock. Fifteen awake dogs were given Escherichia coli endotoxin IV. Within 5 min, CO decreased to 28%, LV dP/dt to 46%, and MAP to 52% baseline. Fifteen minutes after endotoxin, five dogs each received naloxone, AVP antagonist, or no treatment. Control (untreated) animals exhibited persistent cardiovascular depression, with CO 49%, LV dP/dt 69%, and MAP 91% of baseline after 45 min. Naloxone improved CO to 69%, LV dP/dt to 94%, and MAP to 91% by 30 min after treatment. AVP blockade improved CO to 105%, LV dP/dt to 107%, and MAP to 95% of baseline by 30 min after treatment, and caused significant tachycardia. Plasma cortisol and AVP increased markedly in all groups after endotoxin administration. AVP antagonist treatment increased mean survival from 1.4 to 4 days. These data suggest that abnormally elevated AVP contributes to cardiovascular depression in canine endotoxin shock and that AVP blockade is therapeutic in the animal model studied.
 ...
PMID:The role of endorphins and vasopressin in canine endotoxin shock. 294 95

Using the opiate receptor antagonist naloxone, we tested the hypothesis that endorphins act on opiate receptors to cause cardiovascular depression in primate shock. Mean arterial pressure (MAP), cardiac output, and left ventricular contractility (LV dP/dtmax) were measured in 34 anesthetized cynomolgus monkeys. Hemorrhagic shock was induced by bleeding into a heparinized reservoir to achieve (t = 0) and maintain MAP at 45 mm Hg. At t = 60 min, the reservoir was clamped and the animals were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 5) or 0.9% NaCl as a control (n = 5). There were no significant differences in the cardiovascular responses to naloxone and saline when acid-base balance and core body temperature were not controlled. Pressor responses to naloxone, however, were present in proportion to arterial pH and body temperature. When these factors were controlled, naloxone (n = 6) significantly increased MAP and LV dP/dtmax by 48% and 83%, respectively, whereas saline (n = 6) had no significant effect. Blood was reinfused at t = 120 min, and survival rate at 72 h was significantly (p = .01) higher with naloxone (3/6) than saline controls (0/6). In the endotoxic shock model, cynomolgus monkeys were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 6) or 0.9% NaCl (n = 6) when MAP reached 75 mm Hg or its nadir 60 to 90 min after Escherichia coli endotoxin, 5 mg/kg iv. Naloxone significantly increased MAP and LV dP/dtmax by 24% and 22%, respectively, whereas saline had no effect. Survival rate at 48 h was significantly (p = .01) higher with naloxone (6/6) than saline (1/6). Plasma beta-endorphin and beta-lipotropin concentrations rose three to five-fold in both shock models and were not affected by treatment. We conclude that endorphins are activated in primate shock and act on opiate receptors to contribute to the cardiovascular depression found with hemorrhage and endotoxemia.
 ...
PMID:Evidence for a role of endorphins in the cardiovascular pathophysiology of primate shock. 296 36

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 micrograms/kg, alfentanil, 20 micrograms/kg, was given, followed by a continuous infusion of 1 microgram/kg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 micrograms/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartmental moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 +/- 2.2 mL/kg/min and 6.3 +/- 0.8 mL/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alfentanil in infants and children with congenital heart defects. 297 28

Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation were recorded from muscle cells of the rabbit isolated mesenteric artery. At 0.03 Hz the e.j.p. amplitudes were stable. When a train of fifteen pulses was applied at 0.25 Hz or at higher frequencies (0.5, 1 and 2 Hz), e.j.p.s showed an initial facilitation followed by depression. [Met5]enkephalin 0.1 and 1 mumol/l, [D-Ala2,D-Leu5]enkephalin 0.1 and 1, but not 0.01 mumol/l, and [D-Pen2, L-Pen5]enkephalin 3 mumol/l all depressed the e.j.p.s evoked by trains of fifteen pulses at 1 Hz. When more than one concentration was used ([Met5]enkephalin, [D-Ala2,D-Leu5]enkephalin), the inhibition was concentration dependent. It was always greater for the first few e.j.p.s than for the later ones in a train. [Met5]enkephalin 1 mumol/l reduced the first e.j.p. at 1 Hz and the e.j.p.s evoked by 0.03 Hz to a similar extent. The inhibitory effect of [Met5]enkephalin 1 mumol/l on e.j.p.s persisted in the presence of yohimbine 0.3 mumol/l. Naloxone 1 mumol/l did not interfere with the effect of [Met5]enkephalin 1 mumol/l. Naloxone 10 mumol/l depressed some e.j.p.s and prevented the inhibition by [Met5]enkephalin 1 mumol/l. Neither ICI 154129 10 mumol/l nor ICI 174864 0.3 mumol/l had any effect of their own and both compounds antagonized the action of [Met5]enkephalin 1 mumol/l. Normorphine 10 mumol/l, fentanyl 1 mumol/l, ethylketocyclazocine 0.1 mumol/l, and dynorphin A(1-13) 1 mumol/l were all ineffective. Ethylketocyclazocine 1 mumol/l did not change the e.j.p.s either, but antagonized [Met5]enkephalin 1 mumol/l. [Met5]enkephalin 1 mumol/l failed to influence both the resting membrane potential of the muscle cells and the depolarizing effect of noradrenaline 3 and 30 mumol/l. We suggest that the axon terminals of post-ganglionic sympathetic neurones in the rabbit mesenteric artery possess opioid delta-, but not mu- or kappa-receptors. The activation of presynaptic delta-receptors inhibits the release of the neuroeffector transmitter. There is no evidence for any effect of co-released endogenous opioid peptides under our experimental conditions.
 ...
PMID:Presynaptic opioid delta-receptors in the rabbit mesenteric artery. 303 Dec 83

Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.
 ...
PMID:The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit. 303 45

The usefulness of physostigmine in reversing post-narcotic depression after general anaesthesia is well proven; so is that of naloxone, a specific opioid analgetics antagonist, in reversing neuroleptic anaesthesia effects. Morphine-like analgetics are widely used as premedication agents, too; on the other hand, physostigmine reverses opioids as well as other psychotropic and narcotic agents. For that reason, positive post-narcotic physostigmine effects could be due to its anti-opioid potency as well. In a double-blind, randomised study, physostigmine and naloxone were evaluated using a clinically based vigilance protocol, and compared with saline solution. Naloxone did not have remarkable advantages as compared with placebo, while physostigmine led to a significantly higher level of vigilance; moreover, that level was reached sooner. The positive effects of physostigmine in restoring a sufficient level of vigilance after general anaesthesia are, in respect of our findings, unrelated to its antagonism to morphine-like analgetics.
 ...
PMID:[Pharmacologic modification of vigilance in the postnarcotic phase-- naloxone or physostigmine?]. 305 53

The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.
 ...
PMID:Effect of intravenous enkephalin administration on kallikrein-kinin system in experimental hemorrhagic shock. Evidence for activation of kallikrein-kinin system by naloxone. 307 Feb 4

This report describes a systematic analysis of opiate drug effects on ventilation and its components tidal volume and frequency in intact, awake and unrestrained rats. A whole-body plethysmographic method was used to measure these parameters of respiration while animals breathed air or various concentrations of CO2 in air. Subcutaneous doses of morphine lower than 40 mg/kg exerted little or no apparent effect in rats breathing air; in rats breathing 4 to 8% of CO2 these doses of morphine also failed to depress any of the ventilatory parameters below the level of saline controls breathing air. Doses (0.16 to 160 mg/kg) of morphine blunted the frequency response to CO2 in a biphasic manner. The effects of morphine on tidal volume consisted of a slight increase at 0.16 and 0.63 mg/kg, a dose-dependent decrease at 2.5 to 40 mg/kg and a paradoxical rise at 160 mg/kg. These complex effects of morphine on tidal volume and frequency resulted in a simple sigmoid depression of minute volume. The slope of this sigmoid dose-response curve varied with the inspirate; it increased as the concentration of CO2 was higher. Naloxone antagonized the frequency depression produced by 40 mg/kg of morphine in a dose-dependent manner at doses ranging from 0.01 to 0.16 mg/kg, but frequency decreased again at 0.63 mg/kg. The effects of naloxone on the tidal volume depression consisted of a paradoxical further decrease at 0.01 mg/kg, a dose-dependent antagonism of depression at 0.04 to 0.16 mg/kg and a stimulation above the normal control level at 0.63 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Respiratory effects of morphine in awake unrestrained rats. 308 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>