Epilepsy is a chronic brain disease of diverse etiology; it is characterized by recurrent paroxysmal episodes of uncontrolled excitation of brain neurons. Involving larger or smaller parts of the brain, the electrical discharge is evident in the electroencephalogram (EEG) as synchronized rhythmic activity and manifests itself in motor, sensory, psychic, and vegetative (visceral) phenomena. Because both the affected brain region and the cause of abnormal excitability may differ, epileptic seizures can take many forms. From a pharmaco-therapeutic viewpoint, these may be classified as:

- general vs. focal seizures;

- seizures with or without loss of consciousness;

- seizures with or without specific modes of precipitation.

The brief duration of a single epileptic fit makes acute drug treatment unfeasible. Instead, antiepileptics are used to prevent seizures and therefore need to be given chronically. Only in the case of status epilepticus (a succession of several tonic-clonic seizures) is acute anticonvulsant therapy indicated — usually with benzodiazepines given i.v. or, if needed, rectally.

The initiation of an epileptic attack involves "pacemaker" cells; these differ from other nerve cells in their unstable resting membrane potential, i.e., a depolarizing membrane current persists after the action potential terminates.

Therapeutic interventions aim to stabilize neuronal resting potential and, hence, to lower excitability. In specific forms of epilepsy, initially a single drug is tried to achieve control of seizures, valproate usually being the drug of first choice in generalized seizures, and car-bamazepine being preferred for partial (focal), especially partial complex, seizures. Dosage is increased until seizures are no longer present or adverse effects become unacceptable. Only when monotherapy with different agents proves inadequate can changeover to a second-line drug or combined use ("add on") be recommended (B), provided that the possible risk of pharmacokinet-ic interactions is taken into account (see below). The precise mode of action of antiepileptic drugs remains unknown. Some agents appear to lower neuronal excitability by several mechanisms of action. In principle, responsivity can be decreased by inhibiting excitatory or activating inhibitory neurons. Most excitatory nerve cells utilize glutamate and most inhibitory neurons utilize y-ami-nobutyric acid (GABA) as their transmitter (p. 193A). Various drugs can lower seizure threshold, notably certain neu-roleptics, the tuberculostatic isoniazid, and p-lactam antibiotics in high doses; they are, therefore, contraindicated in seizure disorders.

Glutamate receptors comprise three subtypes, of which the NMDA subtype has the greatest therapeutic importance. (N-methyl-D-aspartate is a synthetic selective agonist.) This receptor is a ligand-gated ion channel that, upon stimulation with glutamate, permits entry of both Na+ and Ca2+ ions into the cell. The antiepileptics lamotrigine, phenytoin, and phenobarbital inhibit, among other things, the release of glutamate. Felbamate is a glutamate antagonist.

Benzodiazepines and phenobarbital augment activation of the GABAa receptor by physiologically released amounts of GABA (B) (see p. 226). Chloride influx is increased, counteracting depolarization. Progabide is a direct GABA-mimet-ic. Tiagabin blocks removal of GABA from the synaptic cleft by decreasing its re-uptake. Vigabatrin inhibits GABA ca-tabolism. Gabapentin may augment the availability of glutamate as a precursor in GABA synthesis (B) and can also act as a K+-channel opener.

Drugs used in the treatment of status epilepticus: Benzodiazepines, e.g., diazepam

Waking state


Do Not Panic

Do Not Panic

This guide Don't Panic has tips and additional information on what you should do when you are experiencing an anxiety or panic attack. With so much going on in the world today with taking care of your family, working full time, dealing with office politics and other things, you could experience a serious meltdown. All of these things could at one point cause you to stress out and snap.

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