Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated in mice the effects of several drugs which may be administered as part of an anaesthetic technique on the convulsive threshold to laudanosine and to strychnine, which is reported to have a similar mechanism of action. I.v. administered propofol, thiopentone and midazolam increased the dose of convulsant necessary to produce seizure when administered 2 min before the convulsive stimulus. In contrast, methohexitone and etomidate exhibited a proconvulsant effect, although with the latter this was significant only in laudanosine-treated mice. Pethidine was proconvulsant in both laudanosine- and strychnine-treated mice, but morphine was proconvulsant only in strychnine-treated mice. The effects of morphine, but not pethidine, were antagonized by naloxone 1 mg kg-1. Laudanosine, but not strychnine caused arousal from anaesthesia in subconvulsive doses. This and other evidence suggests that the mechanism of the CNS excitation produced by strychnine and laudanosine are not the same.
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PMID:Modification by drugs used in anaesthesia of CNS stimulation induced in mice by laudanosine and strychnine. 175 Dec 75

Meperidine neurotoxicity manifests as shakiness, tremors, myoclonus, and seizures. It is generally seen with repeated parenteral use. We report a case of meperidine neurotoxicity from oral use by an otherwise healthy woman. The pharmacology and clinical implications are discussed.
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PMID:Neurotoxicity of meperidine. 403 66

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

The influence of centrally administered meperidine, normeperidine and pentazocine on the excitability of brain was studied by measuring the threshold for flurothyl-induced convulsions in rats. All three opioids are reported to lower seizure thresholds when given subcutaneously to rats in this test. Dose-and time-dependent changes in the seizure threshold occurred after intracerebroventricular injection of pentazocine (10-160 micrograms), meperidine (25-150 micrograms) and normeperidine (50-150 micrograms). Rapid increases in the seizure threshold were associated with pentazocine and meperidine, whereas a slowly developing decrease in the threshold was caused by normeperidine. Naloxone (10 mg/kg, s.c.) antagonized the anticonvulsant effect of meperidine (but not that of pentazocine) and enhanced the proconvulsant effect of normeperidine. Thebaine (25-150 micrograms), which had no marked influence on the seizure threshold when given intracerebroventricularly, lowered the threshold after subcutaneous injection of 12.5 and 25 mg/kg. This effect was not altered by injection of naloxone. These results show that centrally administered opioids can act on excitatory or inhibitory systems that regulate seizure mechanisms in the rat brain. Furthermore both naloxone-sensitive and naloxone-insensitive components are involved. Meperidine, pentazocine and thebaine have different actions on the seizure threshold after intracerebroventricular, as opposed to subcutaneous, administration. This work has, therefore, identified the route of administration as a critical variable in the effect of opioids on the seizure threshold in rats.
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PMID:Studies on the excitatory and inhibitory influence of intracerebroventricularly injected opioids on seizure thresholds in rats. 647 79

Meperidine is a widely prescribed opioid analgesic used in a variety of clinical situations. The parent compound has central nervous system depressant effects. However, the sole active metabolite, normeperidine, is a central nervous system excitatory agent and has the ability to cause seizures, especially in patients with renal failure. Patients with normal renal function rarely manifest seizure activity when given meperidine, but if the drug is used in large doses at frequent dosing intervals, seizures may occur. Reported here is the case of a man with normal renal function who had a tonic-clonic seizure due to meperidine that was administered for the pain of underlying chronic pancreatitis.
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PMID:Meperidine-induced generalized seizures with normal renal function. 916 82

Mu opiate agonists morphine, fentanyl and meperidine are administered short-term to pediatric patients, from the neonatal period through adolescence. However, there has been no assessment of the effect of age on the analgesic efficacy or the concentration-response relationship for these opioids in human pediatric patients. Few studies in animals have correlated opioid anti-nociception and tissue levels of these opioids commonly administered to pediatric patients. The present study was conducted to examined the role of age on opioid anti-nociceptive potency and efficacy and brain and plasma opioid levels to provide predictive information on the effect of opioids in developing humans. Administration of trace amounts of tritiated drug with anti-nociceptive doses of unlabeled drug was used for the assessment of anti-nociception in the tail-flick test and for the measurement of brain and plasma drug equivalent levels in postnatal rats (PND 3-21). Morphine and fentanyl were completely efficacious in all postnatal ages examined, although age-related differences in drug potency, as well as, differences in brain and plasma levels were observed. There was a good correlation between morphine (r = 0.96) and fentanyl (r = 0.89) ED(50) values and their respective brain and plasma EC(50) equivalent levels. Meperidine had limited efficacy in young rats (PND 3-9) but was completely efficacious in older rats (PND 14-17). However, PND 21 rats experienced tonic-clonic seizures which limited its efficacy to 70% anti-nociception. Our data suggest that pharmacokinetics, the development of the blood-brain barrier and ontogeny of opioid receptor function may play important roles in the sensitivity of postnatal rats to mu receptor agonists.
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PMID:Ontogeny of mu opioid agonist anti-nociception in postnatal rats. 954 44

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
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PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

Musculoskeletal injuries secondary to seizures are well documented and have a variable incidence. Meperidine (Demerol [Abbott, Abbott Park, IL]) has been used for many years in the postoperative setting for pain control; however, in high doses, it has been associated with seizure. We report the case of patient who experienced a tonic-clonic seizure 5 days after hip revision surgery, resulting in dissociation of the socket from the acetabulum with an associated acetabular fracture. In this patient, meperidine administered for patient-controlled analgesia within recommended range caused the seizure.
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PMID:Meperidine-induced seizure after revision hip arthroplasty. 1580 67

Opioids have been used for analgesia in nearly all civilizations. In paediatrics their use has become widely accepted for combating severe pain, especially postoperative pain and tumour pain. Receptors in the central nervous system are the best known sites of action of opioids, but the existence of peripheral receptors is also probable. The action depends on whether the opioid is more agonist or antagonist and on the peculiarities of physiology in childhood: in the small child a hyperdynamic blood circulation makes resorption faster, and in newborn and premature infants distribution and excretion are influenced by the different composition of the body and the immaturity of liver and kidney. The best known opioid is morphine, and it is the reference substance with which all other opioids are compared. Fentanyl has been used even for the smallest ventilated prematures in recent times, as it is easy to manage and has an early onset of action. Its depressant action on the respiratory centre is an advantage when attempts of spontaneous breathing make mechanical ventilation difficult. Obstinate constipation is the disadvantage of both morphine and fentanyl, and an exacerbation of hyperbilirubinaemia has been seen with fentanyl. Nalbuphine causes a lower degree of respiratory depression. The newer opioids alfentanil and sufentanil have already been used for the relief of paediatric postoperative pain and during mechanical ventilation, but no special advantages of their use are reported. Meperidine has been favoured especially for postoperative pain, although it appears to have no advantages over morphine. Its active metabolite normeperidine may accumulate and cause seizures; meperidine should not be used in prematures or in children with renal dysfunction. There are few publications on the use of piritramide in paediatric pain. Tramadol is widely used for emergencies, as it has the least sedative action; but it has disadvantages in causing nausea and vomiting. Codeine is widely used for its antitussive action. While the necessity of good analgesia for even the smallest infant cannot be overstated, the opioid used must be carefully selected with reference to the age of the child and the pain to be controlled.
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PMID:[Analgesia with opioids in the paediatric patient.]. 1841 33

Meperidine is an opiod analgesic used in a variety of clinical situations. The active metabolite, normeperidine, is a central nervous system excitatory agent and has the ability to cause irritability, hyperreflexia, tremor, myoclonus and seizures. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and co-adminestration of hepatic enzyme inducing medications or phenothiazines which decreases seizure treshold. Patients with normal renal function rarely manifest seizure activity when given meperidine. Here we report a 10 year old boy with a femur fraction who had normal renal function. We used low dose meperidine due to post operative pains.
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PMID:[Convulsion due to application of low dose meperidine: a case report]. 2336 82


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