Induced Seizures

Various animals show spontaneous epilepsy or seizures that can be readily induced by sensory stimulation (see Jobe et al. 1991). Tottering mice display seizures that resemble absence attacks behaviourally, in their EEG pattern and response to drugs. DBA/2 mice show reflex seizures to audiogenic stimuli while photically-induced seizures can be obtained in the Senegalese baboon, Papiopapio, which are similar to generalised tonic-clonic epilepsy. 

The widespread and diverging nature of ascending monoamine pathways to the cortex suggest that NA and 5-HT are more likely to have a secondary modifying rather than a primary effect on the initiation of epileptic activity. In reality this is the case and their secondary role is even a minor one. Generally a reduction in monoamine function facilitates experimentally induced seizures (see Meldrum 1989) while increasing it reduces seizure susceptibility. The variability of the procedures used and results obtained do not justify more detailed analysis here. 

Phenobarbitone was the first AED and was introduced in 1912. It was largely replaced in 1932 by phenytoin for the management of tonic-xilonic seizures and partial and secondary epilepsy. Carbamazepine followed, then ethosuximide for absence seizures and valproic acid. These remained, apart from the introduction of the benzodiazepines, the mainstay of therapy until the last decade. They were introduced solely on their ability to control experimentally induced seizures. Their mechanisms of action were unknown and no thought was given to the possibility of NT modification and in fact subsequent research has shown that with the exception of the benzodiazepines none of them work primarily through NT manipulation. They act directly on neuronal excitability. 

List the nonhematologic toxicity to high-dose chemotherapy used in myeloablative preparative regimens, specifically busulfan-induced seizures, hemorrhagic cystitis, gastrointestinal toxicities, and sinusoidal obstruction syndrome. 

Electroconvulsive therapy Administration of electric current to the brain through electrodes placed on the head in order to induce seizure activity in the brain, used in the treatment of certain mental disorders. 

Fanini D, Trieff NM, Sadagopa Ramanujam VM, et al. Effect of acute acrylonitrile exposure on metrazol induced seizures in the rat. Neurotoxicology 6 29-34. 

The answer is c. (Hardman7 p 408.) Clozapine differs from other neuroleptic agents in that it can induce seizures in nonepileptic patients In patients with a history of epileptic seizures for which they are not receiving treatment, stimulation of seizures can occur following the administration of neuroleptic agents because they lower seizure threshold and cause brain discharge patterns reminiscent of epileptic seizure disorders. 

Acute management of toxaphene-induced seizures in humans with anticonvulsants, especially diazepam, phenobarbital, and phenytoin (USPHS 1994). 

There is an increased risk of drug-induced seizures in all patients treated with antipsychotics. The highest risk for antipsychotic-induced seizures is with the use of CPZ or clozapine. Seizures are more likely with initiation of treatment and with the use of higher doses and rapid dose increases. 

Myhrer T, Skymoen LR, Aas P. Pharmacological agents, hippocampal EEG, and anticonvulsant effects on soman-induced seizures in rats. Neurotoxicol. 24 357-367,2003. 

Mulle, C., Sailer, A., Perez-Otano, I., Dickinson-Anson, H Castillo, P. E Bureau, I., et al. (1998) Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 392,601-605. 

Pro-/anticonvulsive potential Stereotyped behavioral changes and electrographic discharges Chemically induced seizures Baraban et al.213... 

Very high doses of caffeine can induce seizures in those with no preexisting seizure disorder. Caffeine also prolongs seizures induced by electroconvulsive treatment in humans (Shapira et al. 1987). Given the... 

Ve ani A, Wu HQ, Angelico P, Stasi MA, Samanin R. 1988. Quinolinic acid-induced seizures, but not nerve ceU death, are associated with extraceUular Ca " " decrease assessed in the hippocampus by brain dialysis. Brain Res 454(1—2) ... 

Wu J, George AA, Schroeder KM, Xu L, Marxer-MUler S, Lucero L, Lukas RJ (2004) Elec-trophysiological, pharmacological, and molecular evidence for alphaT-nicotinic acetylcholine receptors in rat midbrain dopamine neurons, J Pharmacol Exp Ther 311 80-91 Xu J, Lerraro NV, Zhu Y, Lonck C, Deshpande P, Marks MJ, Collins AC, Lester HA, Heinemann SL (2006) Increased sensitivity to nicotine-induced seizures in 32 V287L knock-in mice, Soc Neurosci Abstr 36 326,314/C382... 

Salas R, Cook KD, Bassetto L, De Biasi M (2004) The a3 and 34 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion. Neuropharmacology 47 401 07... 

Coleman BR, Ratcliffe R, Oguntayo S, Shi X, Doctor B, Gordon R, Nambiar M. (2008) [-i-]-Huperzine A treatment protects against A-methyl-d-aspartate-induced seizure/status epilepticus in rats. Chembiol Interact 175 387-395. 

Merremosides B (13) and D (15) exhibited antiserotonergic activity in mice with Dgo values of 10 pg/cm and 2 pg/cm, (c/., promethazine, Dgo 2 pg/cm ) (24). Intraperitoneal administration to mice of tyrianthins VI (91), VIII (scammonin VI, 68), and IX (93) resulted in antidepressant activity. Also, the activities of tryanthi-nic acids I (94) and II (95), and the macrolactones scammonins I (63) and II (64), and tyrianthins VI (91), VIII (68), and IX (93) exhibited dose-dependent protective effects against pentylenetetrazole-induced seizures. Tyrianthin VI (91) and scammonin II (64) produced relaxant effects on spontaneous contractions in the isolated rat ileum. Finally, the administration of compounds 68 and 93-95 to mouse brain slices induced increments in the release of GABA and glutamic acid 48). 

Flumazenil Flumazenil and nalmefene can induce seizures in animals. Remain aware of the potential risk of seizures from agents in these classes. 

Seizures Seizures may be aggravated or may occur in individuals with or without a history of convulsive disorders if dosage is substantially increased above recommended levels because of tolerance. Observe patients with known seizure disorders closely for hydromorphone-, meperidine-, morphine-, or tramadol-induced seizure activity. 

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