Antiepileptic Drugs

Antiepileptic drugs may be classified as follows:

Classification (Chemical)

Hydantoin derivatives

Phenytoin

Fosphenytoin

Iminostilbenes

Carbamazepine (only antiepileptic used in pregnancy)

Oxcarbamazepine

Valproic acid derivatives

Sodium valproate  (valproic acid)

Long acting barbiturates

Phenobarbitone,

Methobarbitone

Deoxy barbiturate

Primidone

Succinimides

Ethosuximide,

Methsuximide,

Phensuximide

Benzodiazepines

Clonazepam,

Nitrazepam

Diazepam

Carbonic anhydrase inhibitors (CAI)

Acetazolamide

Sulthiame

GAMA- vinyl – GABA

Vigabatrin

Phenyltriazine

Lamotrigine

Amino acid derivatives

GABA  pentin

Monosacharide derivatives

Topiramate

Nicotinic acid derivatives

Tiagabine

Sulphonamide derivatives

Zonisamide

Miscellaneous

Paraldehyde

Epilepsy

Epilepsy is a sudden excessive, rapid depolarization of groups of cerebral neurons which may remain localized or which may spread to cause a generalized seizure.

It is an increase in the electrical activity of brain.

It may be:

1. Primary –for which no cause is known, inherited abnormality of brain, treatment is for whole life.
2. Secondary –cause is known. Due to various causes like:

• Infection
• Meningitis
• Encephalitis
• Brain tumor
• Head injury
• Metabolic disturbances, like changes in calcium metabolism, hypoglycemia,
• Excessive hydration
• Sudden withdrawal of alcohol from addict
• Ingestion of drugs promoting convulsions (CNS stimulants –caffeine, nikethamide, methyl phenidate)  

Mechanism

Mechanism is very simple. In brain inhibitory and excitatory neurotransmitters are released. When imbalance occurs, increase in excitement in brain may result.

GABA

GABA is inhibitory, when interference in synthesis, release, reuptake or metabolism occurs, decrease in levels of GABA in brain, leads to increased excitability.

GAD (Glutamic acid decarboxylase)

In patients of epilepsy, decrease in activity of GAD occurs, which is the rate limiting enzyme in synthesis of GABA.

Most drugs act by increasing the levels of GABA, like benzodiazepines, barbiturates, etc.

 Types Of Epilepsy

Primary generalized tonic clonic (grand mal)

Most common type encountered in patients. Increased activity of groups of cerebral neurons occurs, which rapidly spreads to other parts of the brain. There is immediate loss of consciousness followed by tonic and clonic convulsions.

Tonic convulsions	Clonic convulsions
Simultaneous contraction, flexion and extension of muscles	Alternate flexion and extension of muscles

After convulsions, patient is confused and drowsy.

 Drugs of 1st choice                

• Phenytoin 300-400 mg/d
• Valproate 1000-3000 mg/d
• Carbamazepine 600-1200 mg/d
• Lamotrigine 100-300 mg/d

Alternatives

• Phenobarbitone 120-250 mg/d
• Primidone 750-1500 mg/d
• Topiramate 50-600 mg/d

Partial, including secondarily generalized

No abnormal convulsions occur, only part of body which is controlled by hyper excitable part of brain. There is no loss of consciousness and abnormal contractions of muscles. Abnormal mental changes and movements include diarrhea, urination, sensory and motor changes in person.

Drugs used are same as above except clonazepam.

Absence seizures (petit mal)

Brief, abrupt loss of consciousness in patient which may be manifested by:

1. Rapid eye blinking
2. Sudden black out
3. Patient walking falls down, rises, and starts walking again
4. Abrupt loss of consciousness, which is self limiting
5. Mental changes for moment.

Drugs of choice                      

• ethosuximide 750- 2000 mg/d
• valproate 1000-3000 mg/d

Alternatives

• Clonazepam 1.5-20 mg/d
• Lamotrigine 100-300 mg/d

Atypical absence, myoclonic, atonic 

Rapid contraction of group of muscles, which is recurrent for several minutes. This type is due to neurological damage in brain (encephalitis, infections, hypoxia, uremia, poisoning with drugs) due to neurological damage.

Drugs of 1st choice                

            valproate 1000-3000 mg/d

Alternatives

• Clonazepam 1.5-20 mg/d
• Lamotrigine 100-300 mg/d

Status epilepticus

Grand mal seizures are recurrent, without gaining consciousness, called status epilepticus. This is a medical emergency, as death may occur due to respiratory failure, so drugs are always given I/V.

Drugs of choice are:

• diazepam 1/v 5-10 mg
• phenytoin i/v 15-20 mg/kg (fosphenytoin is safer)
• phenobarbitone i/v 10-20 mg/kg

Refractory status-with full intensive care support

Seizures are not controlled even by these drugs, then give:

• Thiopentone sodium
• propofol
• midazolam

Diazepam is used for control of convulsions.

Continue Reading

Phenytoin Sodium

Carbamazepine and Oxcarbamazepine

Valproic Acid

Phenobarbitone, Methobarbitone, Primidone and Succinamides

Benzodiazepines as Antiepileptics

Acetazolamide, Sulthiame and Newer Antiepileptics

Browse all articles on Drugs Acting on Central Nervous System