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)

In order to investigate the mechanisms leading to respiratory depression after lumbar administration of opioids, plasma and ventricular CSF pharmacokinetics of intrathecal meperidine (1 mg.kg-1) were studied in five head-injured patients undergoing surgery for lower limb fracture. Meperidine was detected both in the plasma (arterial catheter) and in the ventricular CSF (intracranial catheter) soon after intrathecal administration: 45 +/- 17 min and 100 +/- 14 min, respectively. The maximal plasma concentration was 341 +/- 133 ng.ml-1, whereas, in ventricular CSF, it was 64.5 +/- 14.9 ng.ml-1. The ventricular CSF-plasma ratio increased with time (r = 0.82) from 0.18 +/- 0.04 at the first hour to 0.38 +/- 0.1 at 16th hour. It is concluded that the putative risk of respiratory depression appears to be mainly related to the absorption into the systemic circulation and to redistribution back into CSF.
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PMID:Arterial and ventricular CSF pharmacokinetics after intrathecal meperidine in humans. 272 38

Meperidine HCl was administered intramuscularly by hand-syringe to a number of individuals representing several species of cetaceans (n = 95) and pinnipeds (n = 36). Dosage administered was 0.11 mg/kg, 0.23 mg/kg or 0.45 mg/kg, with the majority of animals receiving the middle dosage. Meperidine HCl provided moderate restraint in cetaceans without obvious deleterious effects. Restraint was achieved rapidly, with maximum effect occurring 20 min after intramuscular injection and lasting for 2 to 3 hr. Analgesia appeared to last as long as 4 hr and was sometimes accompanied by a restoration of appetite in animals suffering from physical discomfort. Higher doses produced increased sedation and analgesia without noticeably depressing respiration. Meperidine HCl provided moderate restraint for phocids and walrus (Odobenus rosmarus) without apparent detriment. California sea lions (Zalophus californianus) showed little restraint, but demonstrated profound respiratory depression.
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PMID:The use of meperidine hydrochloride for chemical restraint in certain cetaceans and pinnipeds. 319 67

Eleven male patients undergoing endoscopic resection for prostatic adenoma and bladder tumours under spinal anaesthesia received intrathecal pethidine 1 mg X kg-1. Plasma concentration and its evolution with time were assessed; pethidine plasma concentrations were determined by high performance liquid chromatography. Pethidine was rapidly and extensively absorbed. The peak plasma concentration of pethidine was 176 +/- 66 ng X ml-1 (range: 84-208) and the time to peak concentration was 2.3 +/- 1.4 h (range: 0.5-6 h). The terminal elimination half-life was 7.2 +/- 2.2 h (range: 4-11.5 h). The plasma concentrations of pethidine remained below 500-700 ng X ml-1, the minimum concentration necessary to obtain a systemic analgesic effect. Two patients required noramidopyrine as a complement at the 8th and 12th h respectively. No respiratory depression was observed. Intrathecal pethidine (1 mg X kg-1) was an effective agent for spinal anaesthesia: the prolonged postoperative analgesia was due to the drug acting on opioid receptors in the spinal cord. This led to the necessity of postoperative monitoring during 24 h after intrathecal pethidine administration.
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PMID:[Pharmacokinetics of pethidine after spinal anesthesia. Clinical implications]. 357 43

The main reason for premedication is the reduction of preoperative stress. Despite the proven fact that benzodiazepines best reduce preoperative stress, combinations of opioids and neuroleptic drugs are preferred for premedication by many on reviewing the journal Der Anaesthesist. This double-blind study was performed to investigate midazolam and meperidine/promethazine for intramuscular premedication. Method. 60 patients undergoing minor gynecological surgery were randomly assigned to receive either 5-7.5 mg midazolam or 50-75 mg meperidine and 25-50 mg promethazine intramuscularly 30-90 min before surgery. Anxiety, depression, and asthenia were assessed by the patient before and after premedication but before induction of anesthesia using visual analogue scales and a nominal scale. Sedation was assessed by an observer. Heart rate and blood pressure were the physiological stress parameters. Parameters of acceptance and side effects were registered perioperatively. Results. Midazolam had a significantly better anxiolytic and antidepressive effect. There were no differences in the other parameters except for adverse effects. Meperidine/promethazine produced significantly more side-effects than midazolam. The parameters of acceptance assessed the day after surgery were comparable. Conclusions. We conclude from these results that anesthesiologists still premedicate with meperidine/promethazine because the patients accept this premedication very well when asked the day after surgery. Nevertheless, premedication with midazolam provides significantly better anxiolytic and antidepressive effects with significantly less side-effects. Therefore, midazolam should be preferred to meperidine/promethazine for intramuscular premedication.
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PMID:[Midazolam and pethidine/promethazine for intramuscular premedication]. 363 95

The respiratory effects of meptazinol 1 mg kg-1 have been compared with those of pethidine 0.5 mg kg-1 and 1 mg kg-1 in a double-blind trial in 30 patients undergoing arthroscopic meniscectomy under general anaesthesia. Respiratory depression was seen in all treatment groups. Pethidine 1 mg kg-1 produced respiratory depression which was greater than that produced by meptazinol 1 mg kg-1. The least depressant respiratory effects were seen in the group receiving pethidine 0.5 mg kg-1. We submit that the measurement of tidal volume enhances the assessment of the respiratory effects of analgesic drugs during anaesthesia.
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PMID:Meptazinol--a cause of respiratory depression in general anaesthesia. 393 61

The action of meperidine was investigated on the frog sciatic nerve-sartorius muscle in vitro. Meperidine (5 X 10(-5) M to 2 X 10(-4) M) depressed the twitch response to nerve stimulation but potentiated the response to direct muscle stimulation. When the nerve terminal action potential and the endplate potential (EPP) were recorded simultaneously, the EPP was depressed by meperidine but only a small and variable decrease in the nerve terminal action potential was observed which did not produce the EPP depression. The depression of the EPP was partly antagonized by naloxone (3 X 10(-8) M). Meperidine also depressed the EPP produced by iontophoresis of acetylcholine onto the endplate, but this depression was not antagonized by naloxone. It is concluded that there are two meperidine actions on junctional transmission in this preparation. One, a depression of the prejunctional transmitter release process. This depression is partly, if not completely, opiate receptor-mediated. The second is a depression of the response of the endplate to acetylcholine. The latter effect does not involve a naloxone-sensitive opiate receptor.
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PMID:Dual action of meperidine on the frog neuromuscular junction: a prejunctional, opiate receptor-mediated depression of transmitter release and a postjunctional, nonopiate receptor effect on the endplate. 611 16

In this article, an attempt has been made to review the use of receptor stimulating pure agonist opioids in anesthesia, especially in patients with cardiovascular disease. Particular emphasis has been placed on the use of opioids in high doses to produce anesthesia, techniques that recently have become popular in cardiovascular anesthesia. A major benefit of opioid anesthesia is the cardiovascular stability obtained during induction and throughout operation, even in patients with severely impaired cardiac function. There is a considerable body of evidence to support this claim when fentanyl is used. Anesthetic doses of morphine are associated with a higher incidence of cardiovascular disturbances and other problems, and, therefore, more attention to detail is required in order to achieve adequate anesthesia and hemodynamic stability. Although other opioids have been used as sole or principal agents in anesthesia for cardiovascular surgery, none have gained widespread acceptance. Meperidine, for example, which is widely used in lower (nonanesthetic) doses as a supplement to nitrous oxide in cardiac and noncardiac surgery, has proved unsuitable because of severe hemodynamic disturbances when high doses are given. However, initial reports concerning two of the newer agonist opioids, sufentanil and alfentanil, suggest that they may prove to be suitable alternatives and perhaps provide advantages over morphine and fentanyl in patients with or without cardiovascular disease. Although cardiovascular stability usually can be assured in the chronically sick cardiac patient with opioid anesthesia, this is not always so with the healthier patient, particularly those presenting for coronary artery surgery. A frequently occurring problem in these patients is hypertension during or after sternotomy, which can result in myocardial ischemia and infarction. The incidence of severe hypertension (increases in systolic blood pressure greater than 20% of control values) can be reduced drastically by increasing the dose of opioid, e.g., up to 140 micrograms/kg of fentanyl. However, despite such large doses, some patients will continue to need treatment with vasodilators, inhalation anesthetics, or other supplements at certain periods during cardiovascular operations. The use of very large doses of opioids also will prolong postoperative respiratory depression. High doses of opioids can reduce or prevent the hormonal and metabolic responses to the stress of surgery. However, even very large doses of fentanyl or its newer analogues do not prevent marked increases in plasma catecholamine concentrations in response to cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. 615 Jun 63

Meperidine and its principle metabolite, normeperidine, were given intravenously to four non-human primates prior to cesarean delivery in an equivalent dose for human parturients. The status of the infants regarding neonatal depression was assessed at delivery. Repeated blood samples from both the mother and the neonate were obtained over a period of 4 days. The levels of meperidine and normeperidine were analyzed. The results showed that the metabolism of meperidine and normeperidine in the non-human primate was essentially the same as that observed in the human parturient. In addition, normeperidine appeared to be more toxic than meperidine to the neonate. Finally, there does not appear to be an evidence for neonatal metabolism of meperidine to normeperidine.
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PMID:Meperidine and normeperidine metabolism in the rhesus monkey. 615 17

The effect of meperidine on the spontaneous release of acetylcholine (mepp amplitude and frequency) and on the release evoked by nerve stimulation (epp amplitude and quantal content) was investigated in frog sciatic nerve-sartorius muscle in vitro. Meperidine (8.5 X 10(-5) or 1.6 X 10(-4)M) had no effect on mepp frequency recorded intracellularly in the absence of neuromuscular blockers, but reduced mepp amplitude. This depression was not antagonized by 3 X 10(-8) M naloxone and was explained by a nonspecific depressant action of meperidine on the endplate. When mepps and epps were recorded intracellularly in the presence of high Mg++, the mean amplitudes of both potentials were reduced equally by meperidine (either 1.6 or 4.2 X 10(-4)M) i.e. there was no change in the quantal content, and 3 X 10(-8)M naloxone failed to antagonize these amplitude depressions. When epps were recorded in the presence of d-tubocurarine, the percentage depression of epp amplitude by meperidine was significantly greater than found in the presence of Mg++ and was partially antagonized by naloxone indicating an opiate receptor mediated effect of meperidine. Thus it was concluded that Mg++ prevents this prejunctional opiate receptor mediated depressant effect of meperidine on the evoked release of acetylcholine.
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PMID:Mg++ antagonism of a prejunctional opiate receptor mediated effect at the frog neuromuscular junction. 629 95

In an effort to identify delta-receptor-specific properties for opioid modulation of seizure activity, studies were conducted with ICI 154,129, a putative delta-receptor antagonist, in the rat flurothyl test. Rats were pretreated i.c.v. with ICI 154,129 (50 micrograms) which, at this dose, does not alter normal seizure thresholds. Mean seizure thresholds for control groups (i.c.v. saline) ranged between 323-349 sec. In this test, D-Ala2-D-Leu5 enkephalin (20 micrograms, i.c.v.), metkephamid (40 mg/kg, s.c.), and etorphine (20 micrograms/kg, s.c.) raised seizure thresholds by 117, 128, and 140% of control, respectively. Meperidine (25 mg/kg, s.c.) lowered seizure thresholds by 14% less than control. Pretreatment with ICI 154,129 failed to antagonize the proconvulsant action of meperidine or the anticonvulsant and behavioral depressant actions of etorphine. The increases in seizure threshold produced by DADL and metkephamid (two delta-directed ligands) were significantly attenuated by ICI 154,129. However, the DADL-induced wet-shakes, rigid immobility, and behavioral depression were insensitive to ICI 154,129. These data indicate that ICI 154,129 possesses delta-receptor antagonistic properties in this in vivo model of seizure activity. Furthermore, since only the changes in seizure threshold were antagonized, it may be inferred that opioid-induced behavioral depression and DADLE wet-shakes are not a function of delta-receptor activity.
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PMID:A selective role for delta-receptors in the regulation of opioid-induced changes in seizure threshold. 631 16


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