Benzodiazepines antiepileptics effects

Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an IV benzodiazepine, will usually be... 

Side effects. Because clobazam has been widely used as an anxiolytic, its side effects are well known and essentially similar to those of the other benzodiazepines. Thus sedation, dizziness, ataxia, blurred vision and diplopia are the most commonly reported in epileptic patients. One of the most problematic features of clobazam is its tendency to produce tolerance, an effect which may occur more frequently with clobazam than with the other widely used benzodiazepine, clonazepam. It has been estimated that at least 50% of patients develop tolerance. Tolerance to the sedative effects of the drug develop more rapidly than those to the antiepileptic effect. Clobazam should be considered as adjunctive therapy whenever treatment with a single first-line drug has proven to be ineffective. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Once the first dose of benzodiazepine is given, an antiepileptic drug must be started to prevent further seizures from occurring. AEDs must not be given as first-line therapy since they must be infused relatively slowly to avoid adverse effects, delaying their onset of action. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Treatment will call upon dopamine agonists, opioid medications, a benzodiazepine (clonazepam) that increases total sleep time, and drugs most commonly used as antiepileptic medication, such as gabapentin or equivalent. Dopamine agonists are the most effective and reduce the sleep deprivation and the patients complaints. But not all patients respond to dopamine agonists and methadone has been prescribed in the most refractory cases (21). 

Trazodone Hydrochloride Trazodone overdose causes severe toxic effects. These effects are severe if taken along with benzodiazepines or alcohol. Trazodone interacts with MAOIs, cardiovascular drugs, CNS depressants, and antiepileptics. 

It is generally accepted that there is a good correlation between potentiation or antagonism of experimentally induced convulsions in animals and effects observed in man (Kupferberg 2001). Most substances with antiepileptic properties in man antagonize experimental convulsions, whereas many substances which either induce convulsions or lower the convulsive threshold in man (certain CNS stimulants, some neuroleptics) show similar effects in animals. There are nonetheless differences in the efficacy of certain substances in antagonizing experimental convulsions. For example, sodium valproate appears to be more widely effective in different experimental models than benzodiazepines (Loscher 2002). 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

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