Drugs used to treat epilepsy

It is not known what causes epileptic seizures, but suggestions include increased excitatory nerve transmission, decreased inhibitory transmission or some abnormality of the nerve cells themselves. Such abnormalities may be the result of head trauma, stroke or tumours, but in most cases, the cause is unknown. 

However, it seems that abnormalities in partial epilepsy are different to those in generalized epilepsy. 

The choice of drug depends on the type of epilepsy. Combination therapy with two or more drugs may be necessary. In this case, careful monitoring is needed because unpredictable interactions between antiepileptic drugs are possible. Withdrawal from antiepileptic drugs should be gradual to avoid the risk of precipitating rebound seizures. 

It is not known exactly how antiepileptic drugs work, but two mechanisms seem to be important for drugs in current use, while newer drugs may work by other means yet to be elucidated. 

Many well-established antiepileptic drugs (for example phenobarbital and benzodiaze pines) are known to facilitate the opening of GABA chloride ion channels at synapses. However, this is not the complete explanation as, for example phenobarbital is far more effective as an anticonvulsant than other barbiturates with the same enhancing effects on GABA. 

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Chapter 15 Update Drugs Used to Treat Epilepsy... 

Drug products with a narrow therapeutic range, such as drugs used to treat epilepsy, asthma, high blood pressure, and heart disease... 

Talampanol (LY300164) is a drug used to treat epilepsy and neurodegen-erative diseases. In an optimized procedure, the first step in its production is enzymatic in nature (Figure 10.4). Zygosaccharomyces rouxii is used to perform a biocatalytic reduction and excellent yields and enantioselectivities have been... 

Phenobarbitone is used to treat epilepsy, migraine headache, dental infections, pregnancy vomiting, tetanus, enuresis, chorea, pre and post operative sedation, hypertension, anxiety states, neurosis, and in the treatment of drug and alcohol addiction. This drug is also called phenobarbital. 

The discovery of benzodiazepines is a story of serendipity and certainly one that is difficult to predictably reproduce as part of a drug discovery program. Regrettably (or fortuitously), this story of the benzodiazepines is not an isolated example. Valproic acid, an agent used to treat epilepsy, migraine, chronic pain, and bipolar affective disorder, was also discovered by accident. 

The cost-effectiveness of four antiepileptic drugs used to treat newly diagnosed adult epilepsy has been studied by cost minimization analysis in 12 European countries (6). The analysis took account of each drug s adverse effects and tolerability profiles. Lamotrigine incurred higher costs than carbamazepine, phenytoin, and valproate, whose costs were similar. 

ANTICONVULSANTS are drugs used to treat convulsions of various types, for instance, in drug or chemical poisoning, e.g. chlorpromazine, diazepam. However, these anticonvulsants are not necessarily effective or suitable for epilepsy. 

Another barbiturate (phenobarbitone (Luminal)) and a newer drug lamotrigine (Lamictal) are used to treat epilepsy. Trazodone (Molipaxin) is a useful anti-depressant with fewer side-effects than some of the older drugs. The action of varenicline (Champix), used to treat smoking withdrawal, has a straightforward mechanism, being a nicotinic partial agonist. 

Carbamazepine and valproate can be effective in bipolar depression that is unresponsive to lithium and appear to exert their action by depressing the limbic system. Both these drugs are normally used to treat epilepsy, see page 218. In bipolar depression, this is an unlicensed use. 

Tiagabine is a drug that inhibits the reuptake of GABA from the synapse, and it has been used to treat epilepsy as well as other convulsant disorders. Because GABA is an inhibitory neurotransmitter in the brain, its prolonged presence can block neurotransmission by other agents, thereby reducing the frequency of convulsions. 

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. 

Various drugs including barbiturates and benzodiazepines, which are used for relieving the severe, convulsive conditions that originate as a result of conditions other than epilepsy, are used in treating epilepsy. It is believed that various mechanisms may be operating within the genesis of epilepsy, and it is possible to influence these mechanisms medicinally. 

Rufinamide is a new triazole derivative with little similarity to other antiseizure drugs. It is approved for use in Lennox-Gastaut syndrome and preliminary evidence suggests that it may also be useful in other difficult-to-treat epilepsy syndromes. 

Now we turn our attention to the antipsychotic potential of drugs that are also useful in treating epilepsy and speculate about the reason for their efficacy in controlling the affective psychoses, especially mania. Manic psychosis is formally like dream psychosis in its delirious aspect we see the ecstatic elation, the grandiose delusions, and the poor judgment leading to social indiscretion in both states. Only organic delirium itself more closely resembles dream psychosis. What could account for these similarities ... 

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). 

There are many drugs that increase the rate of the liver s metabolism. More commonly used medications that fall into this category include rifampin, which is used to treat tuberculosis, and dilantin, phenytoin, and carbamazepine, which are medications commonly used to treat seizures and epilepsy. Chronic alcohol abuse also speeds up the metabolism of the liver. Since all of these substances cause the liver to break down methadone faster then it normally would, one way to correct the problem would be to increase the dose of methadone or break down the dose into several smaller doses given throughout the day. This should only be done on a physician s advice. 

Methamphetamine is also used in other medical situations. People with severe depression are sometimes given short courses of a stimulant such as methamphetamine or amphetamine. However, physicians need to be cautious when giving a person with depression methamphetamine, since there can be a let-down period after stopping the drug that may cause the depression to actually worsen. Methamphetamines are also sometimes used to treat severe cases of epilepsy or Parkinson s disease in which the normally prescribed medications have failed. 

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