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Anticonvulsants

Drugs & Medication

Anticonvulsants

Barbiturates | Benzodiazepines | Carboxamides | Gamma-aminobutyric acid | Potassium bromide

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The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure. Failing this, a good anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic effects that may result in brain damage. An excellent anticonvulsant would have few serious side effects. However, no such drug exists.

Many anticonvulsants block Sodium (Na+) channels, Calcium (Ca2+) channels, AMPA receptors or NMDA receptors. Some anticonvulsants inhibit the metabolism of GABA or increase its release.

In the following list, the dates in parentheses are the earliest approved use of the drug.

Contents

Aldehydes

  • Paraldehyde (1882). One of the earliest anticonvulsants. Still used to treat status epilepticus, particularly where there are no resuscitation facilities.

Aromatic allylic alcohols

  • Stiripentol (2001 - limited availability). Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI).

Barbiturates

Main article: Barbiturates

Barbiturates are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. The following are classified as anticonvulsants:

  • Phenobarbital (1912). See also the related drug primidone.
  • Methylphenobarbital (1935). Known as mephobarbital in the US. No longer marketed in the UK
  • Metharbital (1952). No longer marketed in the UK or US.
  • Barbexaclone (1982). Only available in some European countries.

Phenobarbital was the main anticonvulsant from 1912 till the development of phenytoin in 1938. Today, phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first. Other barbiturates only have an anticonvulsant effect at anaesthetic doses.

Benzodiazepines

Main article: Benzodiazepines

The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant properties. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance and dependency. Of the many drugs in this class, only a few are used to treat epilepsy:

  • Clobazam (1979). Notably used on a short-term basis around menstruation in women with catamenial epilepsy.
    Clonazepam (1974).
    Clorazepate (1972).

The following benzodiazepines are used to treat status epilepticus:

  • Diazepam (1963). Can be given rectally by trained care-givers.
  • Midazolam (N/A). Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa.
  • Lorazepam (1972). Given by injection in hospital.

Bromides

  • Potassium bromide (1857). The earliest effective treatment for epilepsy. There would not be a better drug for epilepsy until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

Carbamates

  • Felbamate (1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

Carboxamides

Main article: Carboxamides

The following are carboxamides:

  • Carbamazepine (1965). A popular anticonvulsant that is available in generic formulations.
    Oxcarbazepine (1990). A derivative of carbamazepine that has similar efficacy but is better tolerated.

Fatty acids

The following are fatty-acids:

  • The valproates valproic acid, sodium valproate, and divalproex sodium (1978).
    Vigabatrin (1989).
    Progabide
    Tiagabine (1997).

Vigabatrin and progabide are also analogs of GABA.

Fructose derivatives

  • Topiramate (1995).

Gaba analogs

  • Gabapentin (1993).
    Pregabalin (2004).

Hydantoins

The following are hydantoins:

  • Ethotoin (1957).
    Phenytoin (1938).
    Mephenytoin
    Fosphenytoin (1996).

Oxazolidinediones

The following are oxazolidinediones:

  • Paramethadione
    Trimethadione (1946).
    Ethadione

Propionates

  • Beclamide

Pyrimidinediones

  • Primidone (1952).

Pyrrolidines

  • Brivaracetam
    Levetiracetam (1999).
    Seletracetam

Succinimides

The following are succinimides:

  • Ethosuximide (1955).
    Phensuximide
    Mesuximide

Sulfonamides

Main article: Sulfonamides

  • Acetazolamide (1953).
    Sulthiame
    Methazolamide
    Zonisamide (1990).

Triazines

  • Lamotrigine (1991).

Ureas

  • Pheneturide
    Phenacemide

Valproylamides (amide derivatives of valproate)

  • Valpromide
    Valnoctamide

References

External links


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