Sedation, anticonvulsant-induced

Sedatives are used clinically to relieve emotional tension, allay anxiety, reduce overactivity, as supplements to analgesic and anesthetic drugs, as anticonvulsants, and most importantly to sedate or induce sleep. 

Pharmacodynamic tolerance, probably on the basis of down-regulation of receptors, develops more rapidly to the effects of barbiturates on mood and sedation than to the anticonvulsant and lethal action. This results in a marked decrease in therapeutic index and the ratio of LD50 and ED50 can approach 1. Furthermore, barbiturates induce P450 enzymes and thus increase their own metabolism resulting in time dependent pharmacokinetic behavior. 

Buspirone does not appear to have a major effect on the BZ-GABA-chloride ionophore complex and, if anything, has some antagonistic interactions with GA-BAergic transmission (although it does not induce seizures) (Jann, 1988 Baldessarini, 1996). The lack of GABAergic effects is evident in the fact that buspirone does not consistently cause sedation, it is not a muscle relaxant, it is not an anticonvulsant, and it does not relieve BZ withdrawal (Jann, 1988 Cole and Yonkers, 1995). 

The leaf essential oil of L. nobilis, which has been used as an antiepileptic remedy in Iranian traditional medicine, was evaluated for anticonvulsant activity against experimental seizures (Sayyah et al., 2002). The essential oil protected mice against tonic seizures induced by maximal electroshock and especially by pentylenetetra-zole. Components responsible for this effect may be methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant doses, the essential oil produced sedation and motor impairment. This effect seems to be related in part to cineol, eugenol and methyleugenol (Sayyah et al., 2002). 

Only phenobarbital strongly induces the synthesis of the hepatic cytochrome P-450 drug metabolizing system. Phenobarbital is contraindicated in the treatment of acute intermittent porphyria. Buspirone lacks the anticonvulsant and muscle-relaxant properties of the benzodiazepines and causes only minimal sedation, v ... 

Enzyme induction can be problematic with co-administration of benzodiazepines and rifampicin or certain anticonvulsants (phenobarbital, phenytoin, carbamaze-pine). However, despite enzyme stimulation, the net effect of adding these anticonvulsants can be augmentation of benzodiazepine-induced sedation. 

Conventional anticonvulsant compounds have been reported to provide limited protection against nerve agent-induced seizures and muscle necrosis when given therapeutically (Lipp, 1972 Clinton et al, 1988). Sedation, tolerance, and abuse potential, however, limit prophylactic use of benzodiazepine compounds. 

Use of St. John s Wort is complicated by the lack of standardisation of the ingredients. Those who wish to take St. John s Wort should be made aware that it may cause dry mouth, dizziness, sedation, gastrointestinal disturbance and confusion. Importantly also, it induces hepatic P450 errzymes (CYP 1A2 and CYP 3A4) with the result that the plasma concentration and therapeutic efficacy of warfarin, oral contraceptives, some anticonvulsants, antipsychotics and HTV protease/reverse transcriptase inhibitors are reduced. Concomitant use of tr5 to-phan and St John s Wort may cause serotonergic effects including nausea and agitation. 

Sedation, fatigue, dizziness, headache, ataxia, and insomnia are less frequent with valproate than with other anticonvulsants. However, encephalopathy, sometimes associated with hyperammonemia and/or liver failure, has been described on several occasions, with symptoms ranging from acute confusion to stnpor and even deep coma (SEDA-18, 69) (9). The stnpor tends to be associated with bilaterally synchronons high-voltage, slow-wave EEG activity. Psychiatric symptoms and increased seizure frequency can also occur. Although in some cases valproate-induced stupor can be associated with increased epileptiform activity, it appeared to be triggered by a cortical non-epileptic mechanism in six... 

Diazepam is used primarily in the treatment of mental anxiety. In addition, it acts as a muscle relaxant for a variety of medical conditions. It may also be used as a sedative-hypnotic and anticonvulsant (e.g., for status epilepticus and drug-induced seizures). Diazepam may also be used to alleviate some of the symptoms associated with the following cholinesterase poisoning, substance abuse withdrawal, antihistamine overdose. Black Widow spider envenomation, and chloroquine overdose. As an anesthetic, diazepam may be used alone or in combination with other drugs for conscious sedation. 

Indications Seizure disorders, anticonvulsants, anxiety, tension and insomnia, surgical adjuncts for conscious sedation or amnesia, skeletal muscle spasms or tremors, delirium, schizophrenia as an adjunct, nausea and vomiting induced by chemotherapy, neonatal opiate withdrawal Common drug examples ... 

Convulsions can be induced in rodents by electric shock applied directly across the cerebrum (ECS), by chemical agents administered peripherally, or even by exposure to noise in specific strains of animals. In safety pharmacology it is particularly important to detect proconvulsant activity. On the other hand, although anticonvulsant activity does not in itself constitute a risk, many substances with anticonvulsant activity, for example, benzodiazepines, induce sedation and memory impairment, which have obvious implications for CNS safety. Both kinds of activity can be seen... 

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