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)

Lidocaine (lignocaine) was given in 42 episodes of status epilepticus (SE) in 36 patients either because of limited pulmonary reserve (22 patients) or because of lack of response to diazepam (14 patients). Lidocaine (1.5-2 mg/kg) was given intravenously in two minutes. A further identical bolus was infused if no response had occurred or if seizures recurred. With the first bolus 11 episodes of SE did not stop, but 31 responded, always in less than one minute. In 19 episodes, however, this response lasted less than 30 minutes. Twelve episodes did not recur, but 30 needed a second bolus because of recurrence. Of these, 19 episodes responded at once but SE reappeared in seven. In these seven episodes the mean control time with the second dose was 102 minutes. Five of these subsequently responded to a continuous infusion of lidocaine. Eleven patients, who had not responded to the first bolus, had no response to the second. Lidocaine is a drug that may be epileptogenic at high doses. At the doses used here, however, lidocaine seems to be a rapid acting anticonvulsant, useful in the short term management of SE and may be indicated in patients in whom respiratory or consciousness depression is undesirable and in those with no response to diazepam. The absence of response to lidocaine indicates SE resistant to treatment and poor prognosis. These data show that prompt lidocaine administration may be worthwhile when management of respiratory depression is not possible.
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PMID:Role of lidocaine (lignocaine) in managing status epilepticus. 154 99

Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy-induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg.kg-1.min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 +/- 5.5, nonpregnant female = 12.1 +/- 4.9, pregnant female = 10.8 +/- 4.1 micrograms/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 +/- 6.3, nonpregnant female = 16.8 +/- 4.5, pregnant female = 16.7 +/- 4.2 micrograms/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats.
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PMID:Pregnancy does not alter the threshold for lidocaine-induced seizures in the rat. 173 99

In Denmark, 6,000-10,000 persons die annually from sudden cardiac death. The majority of these die on account of ventricular fibrillation. A patient is presented here who suffered from recurrent lipothymic seizures which were primarily diagnosed as epilepsy. On account of absence of paraclinical documentation and because of suspected depression, treatment with a cyclic antidepressive agent was commenced, which further increases the tendency to sudden cardiac death. The patient was then brought to hospital with Lidocaine-resistant ventricular fibrillation which responded partly to Ajmalin and partly to Disopyramide. The lipothymic seizures were then interpreted as being precipitated by intermittent malignant episodes of cardiac arrhythmia. During the subsequent six months, the patient has felt well and has been free from lipothymic seizures while receiving 200 mg Mexiletin thrice daily. Attention is drawn to the value of Holter monitoring in the investigation of lipothymic seizures. Lidocaine (despite the existence of resistant cases) must still be considered to be the preparation of first choice on account of extensive knowledge about and confidence in the preparation.
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PMID:[Recurrent ventricular tachyarrhythmias primarily diagnosed as epilepsy]. 202 54

Since most of the toxicity associated with class 1B antiarrhythmic drugs is dose-related, this review examines adverse effects seen in both therapeutic practice and accidental or premeditated overdose. Toxicity is very common with these agents and can be life-threatening. A high percentage of patients must discontinue therapy because of adverse effects. Mexiletine and tocainide are structural analogues of lignocaine (lidocaine) and toxicity is similar with all 3 drugs. With gradual intoxication (the most common form) central nervous system effects such as lightheadedness, dizziness, drowsiness and confusion are seen first. Seizures and respiratory arrest can occur. Cardiovascular toxicity is manifested by progressive heart block, reduced cardiac contraction, hypotension and asystole. Both mexiletine and tocainide may have proarrhythmic effects. Gastrointestinal toxicity is also common. Shock, hypotension, cardiac failure and beta-blocker therapy reduce lignocaine clearance and enhance the risk of intoxication during routine therapy. Both lignocaine and mexiletine elimination is impaired in severe liver disease while tocainide clearance is reduced in renal failure. Management of toxicity is largely supportive and symptomatic. Lignocaine infusion must be discontinued and decontamination of the gut in the case of oral preparations is recommended. Serious intoxication requires intensive care unit admission. Haemodialysis or haemoperfusion may be helpful in serious lignocaine and tocainide poisoning. In institutions where extracorporeal circulatory assistance is available, massive lignocaine poisoning has been successfully treated with this intervention. In the therapeutic setting serious toxicity can be prevented by close clinical surveillance and appropriate dose reduction in patients with reduced drug clearance. Because of the large interindividual variation in lignocaine pharmacokinetic parameters, therapeutic drug monitoring is recommended if results can be reported quickly. Mexiletine and tocainide have stereoselective metabolism and assays do not distinguish the more active isomers. Therapeutic drug monitoring is less useful in this situation.
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PMID:Poisoning due to class 1B antiarrhythmic drugs. Lignocaine, mexiletine and tocainide. 251 64

The finding that the development of lidocaine-kindled seizures is blocked by carbamazepine suggests an interaction of carbamazepine with local anesthetic mechanisms. To study the site of interaction, the effects of lidocaine, carbamazepine and another anticonvulsant drug, phenytoin on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate to the sodium channel gating complex were examined in vitro in a rat brain hippocampus preparation. Lidocaine shifted the concentration inhibition curve of carbamazepine to the right and vice versa. Carbamazepine shifted the concentration inhibition curve of phenytoin to the right and vice versa. The experimentally determined apparent dissociation constants were in a good agreement with the dissociation constants calculated for a one-site model, suggesting that the interaction occurs because lidocaine shares a common binding site with carbamazepine and phenytoin in the voltage-dependent sodium channels.
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PMID:Evidence for a common site of action of lidocaine and carbamazepine in voltage-dependent sodium channels. 255 44

The effects of intravenous lidocaine on the activity of medullary respiratory neuron were studied in urethane anesthetized cats. Using a tungsten microelectrode, spikes from medullary inspiratory neurons were recorded around nucleus ambiguous. Lidocaine was administered using a constant-rate infusion pump until electrographic seizures appeared. The effect of lidocaine on the activity of respiratory neurons showed two types. In one type, consisting of 7 units out of 10, a sequence of changes was observed: the initial stage was represented by increased duration of the burst and decreased frequency of neural discharge; the second stage by desynchronization with mechanical lung inflation; the third stage by continuous activity and the forth stage by decreased spike activity and electrographic seizures. Blood concentration of the lidocaine was 9.6 +/- 3.5 micrograms.ml-1 at the second stage, 15.3 +/- 4.4 micrograms.ml-1 at the third stage, 26.6 +/- 4.1 micrograms.ml-1 at the fourth stage. In another type, consisting of 3 units out of 10, following administration of lidocaine the number of spikes showed only a concentration related depression. Blood concentration of the lidocaine was 6.9 +/- 2.7 micrograms.ml-1 when the spikes disappeared. These results indicate that intravenous lidocaine influences the respiratory rhythm and produces the respiratory depression working in the central nervous system.
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PMID:[The effects of intravenous lidocaine on the activity of medullary respiratory neurons in cats]. 279 39

The anticonvulsive action of lidocaine was tested in mice against a series of convulsants, and its profile of action compared with that of phenytoin. Both agents antagonized seizures induced by ouabain or glutamate (injected i.c.b.), effects attributable to reduction of the sodium conductance of neuronal membranes. Lidocaine and phenytoin were relatively ineffective against convulsants that act on synaptic chloride channels via the GABA-ionophore receptor complex. At higher dose levels, both lidocaine and phenytoin are excitatory within limited ranges. Lidocaine-induced seizures were potentiated by phenytoin, and antagonized by chlordiazepoxide, phenobarbital, valproate, trimethadione and muscimol, but not by ethosuximide. This profile of action is similar to that of bicuculline, suggesting that lidocaine may bind to the GABA recognition site and to another site in the GABA-ionophore receptor complex. Phenytoin-induced excitation was antagonized by chlordiazepoxide, less effectively by phenobarbital or trimethadione, only minimally by valproate, and not by trimethadione or muscimol. Phenytoin is known to bind to picrotoxin and benzodiazepine receptor sites; these findings suggest that it may be excitatory at one or both of these sites.
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PMID:Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts. 290 79

Intravenous lidocaine successfully controlled convulsive status epilepticus in eight patients. Lidocaine was administered, as a diazepam substitute, to elderly patients with chronic obstructive lung disease and to those patients unresponsive to the stated doses of intravenous diazepam. Although transient disappearance of seizures was noted after an initial dose of 100 mg, infusion of 200 mg was necessary to effectively control status. Continuous lidocaine infusion (3.5 mg/kg/h) was used in one case with good results. Undesirable side effects were not seen. The basic mechanisms for possible anticonvulsant action are reviewed. Lidocaine seems to be an effective and safe drug in convulsive status epilepticus. We suggest that lidocaine may be used as a first-line drug, as a diazepam substitute, in the treatment of convulsive status epilepticus in patients in whom respiratory depression is undesirable and in those who do not respond to intravenous diazepam.
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PMID:Intravenous lidocaine for status epilepticus. 340 44

There have been many reports of lidocaine toxicity especially after maternal paracervical block anesthesia. We recently treated a term infant with evidence of fetal distress who presented with symptoms of lidocaine toxicity after maternal pudendal anesthesia. The infant developed apnea and bradycardia soon after birth which responded to mechanical ventilation and epinephrine. A prolonged Q-T interval was noted on day 1 which normalized by day 3. Cord blood was assayed and revealed an elevated lidocaine level. Lidocaine toxicity has been associated with fetal distress secondary to fetal ion trapping in the presence of acidosis. Although good response to supportive therapy occurred in our patient, other methods of therapy such as exchange transfusion and treatment of seizures may be required in some cases. Awareness of this now uncommon syndrome will lead to prompt diagnosis, appropriate work-up, and management.
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PMID:Lidocaine toxicity after maternal pudendal anesthesia in a term infant with fetal distress. 356 84

Neurophysiologic and local cerebral metabolic mapping techniques indicate that seizures associated with lidocaine toxicity originate in subcortical brain structures. Normally local cerebral blood flow (l-CBF) is quantitatively coupled to local cerebral metabolic rate for glucose (l-CMRg). In the present study the response of l-CBF to a lidocaine-induced preconvulsive state (localized seizure activity in the absence of a grand mal seizure) was evaluated in rats anesthetized with 60% nitrous oxide. Lidocaine administered as a bolus (20 mg/kg) followed by an infusion (4 mg/kg) over 5.5 min resulted in progressive alteration in the electroencephalogram (EEG). L-CBF was studied with the 14C-iodoantipyrine autographic method when the preconvulsive EEG pattern consisted of a repetitive spike and wave complex at a frequency of 14 +/- 1 X min-1 complexes, superimposed on practically isoelectric background activity. Under these conditions high doses of lidocaine significantly (P less than 0.05) decreased (range -30% to -68%) l-CBF in 71% of the 34 brain regions studied. The greatest exception to this trend for l-CBF to decrease was observed in the limbic system wherein l-CBF remained within control ranges in eight of the 11 structures evaluated. Qualitative comparison of lidocaine l-CBF changes with l-CMRg changes obtained under similar conditions indicated a general trend for local flow and metabolism to decrease in parallel. Exceptions to this were confined to certain limbic areas (amygdala and hippocampus) in which increases in l-CMRg were more than 100% greater than slight (P greater than 0.05) increases in l-CBF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Local cerebral blood flow during lidocaine-induced seizures in rats. 371 40


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