Absence seizures drugs used

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

Valproic acid has become a major AED against several seizure types. It is highly effective against absence seizures and myoclonic seizures. In addition, valproic acid can be used either alone or in combination with other drugs for the treatment of generalized tonic-clonic epilepsy and for partial seizures with complex symptoms. 

Benzodiazepines and barbiturates are used as anticonvulsant drugs in the treatment of epilepsy. Epilepsy, a medical disorder characterized by recurrent seizures, has many different forms. The four most common seizure types are generalized tonic-clonic seizures (old name grand mal seizures), generalized absence seizures (petit mal seizures), complex partial seizures (psychomotor or temporal lobe seizures), and simple partial seizures (focal seizures). 

Trimethadione, the first oxazolidinedione (Figure 24-3), was introduced as an antiseizure drug in 1945 and remained the drug of choice for absence seizures until the introduction of succinimides in the 1950s. Use of the oxazolidinediones (trimethadione, paramethadione, and dimethadione) is now very limited. 

At least three drugs are effective against absence seizures. Two are nonsedating and therefore preferred ethosuximide and valproate. Clonazepam is also highly effective but has disadvantages of dose-related adverse effects and development of tolerance. Lamotrigine and topiramate may also be useful. 

Valproic acid (Depakene, Depakote, other trade names) is classified as a carboxylic acid, and is used primarily to treat absence seizures or as a secondary agent in generalized tonic-clonic forms of epilepsy. This drug is also used to treat bipolar disorder (manic-depression), especially during the acute manic phase (see Chapter 7). 

Therapeutic uses Phenytoin is highly effective for all partial seizures (simple and complex), for tonic-clonic seizures, and in the treatment of status epilepticus caused by recurrent tonic-clonic seizures (Figure 15.3). Phenytoin is not effective for absence seizures, which often may worsen if such a patient is treated with this drug. 

Succinimides. Ethosuximide (Zarontin) 55 h) differs from other antiepilepsy drugs in that it blocks a particular type of calcium channel that is active in absence seizures (petit mal), and it is used specifically for this condition. Adverse effects include gastric upset, CNS effects and allergic reactions including eosinophilia and other blood disorders, and lupus erythematosus. 

Clonazepam, proprietary name Clonopin, is a benzodiazepine with chemical structure closely related to diazepam. The mechanism of action is the same as described for diazepam, but tolerance does not develop as rapidly as with diazepam. Clonazepam is currently approved for use in absence seizures, infantile spasms, akinetic seizures, and Lennox-Gastaut syndrome. Plasma concentrations associated with maximal effectiveness of the drug range from 15 to 60 ng/mL. At concentrations higher than 80 ng/mL, no additional seizure protection is observed, and toxicity (drowsiness and ataxia) ensues. The most suitable methods adaptable to routine analysis are based on GLC with electron capture detection, although HPLC methods also are effective. ... 

The BZD site is the most thoroughly studied of the three modulatory sites and numerous drugs have been identified that bind to it. About a dozen of these are currently marketed for treating disorders such as generalized anxiety, panic disorders, depression, some forms of epilepsy (e.g. absence seizures), febrile seizures, some sleep disorders (e.g. insomnia), and muscle spasms and cramps and for use as anaesthetics. Flumazenil (11), a BZD antagonist, is currently marketed for treating BZD agonist overdose. 

Phenytoin is effective in many forms of epilepsy, but not absence seizures. Its mode of action appears to be by blocking sodium ion channels. Phenytoin can be a difficult drug to use for the following reasons. 

Mechanism blockade of T-type channels and thalamic neurons 0 Use absence seizures General features of anticonvulsant drug use ... 

List the major drugs used for partial seizures, generalized tonic-clonic seizures, absence and myoclonic seizures, and status epilepticus. 

Absence seizures Ethosuximide and valproic acid are the preferred drugs since they cause minimal sedation. Ethosuximide is often used in uncomplicated absence seizures if patients can tolerate its gastrointestinal side effects. Valproic acid is particularly useful in patients who have concomitant generalized tonic-clonic or myoclonic seizures. Clonazepam is effective as an alternative drug but has the disadvantages of causing sedation and tolerance. 

Withdrawal Withdrawal from antiseizure drugs should be accomplished gradually to avoid increased seizure frequency and severity. In general, withdrawal from anti-absence drugs is more easily accomplished than withdrawal from drugs used in partial or generalized tonic-clonic seizure states. 

Three of the drugs listed are effective in absence seizures. Ethosuximide and valproic acid are not sedating, and tolerance does not develop to their antiseizure activity. Clonazepam is effective but exerts troublesome CNS depressant effects, and tolerance develops with chronic use. At high doses, the drug has a dependence liability like most benzodiazepines. The answer is (A). 

There are two problems with regard to withdrawal from antiseizure drugs the effects of withdrawal itself and the need to continue suppression of seizures. Dose-tapering is an important principle in antiseizure drug withdrawal. As a rule, withdrawal from drugs used in absence seizures is easier than withdrawal from drugs used for partial and tonic-clonic seizures. Withdrawal is most difficult in patients who have been treated with barbiturates and benzodiazepines. The answer is (C). 

Benzodiazepines Diazepam and lorazepam are preferred drugs for status epilepticus. Clonazepam is used for absence seizures. Described in tables 3.8A and 3.8C. 

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