ANTIEPILEPTICS

DEFINITION

Epilepsy Epilepsy is a chronic disorder of brain

function characterized by recurrent seizures often accompanied by episodes of unconsciousness or amnesia.

Seizure Seizure is a transient alteration in

behaviour because of disordered firing of group of neurons.

SEIZURE TYPES

CLASSIFICATION OF ANTIEPILEPTICS

HYDANTOINS-Phenytoin, Mephenytoin BARBITURATES- Phenobarbotone,

Mephobarbitone DEOXYBARBITURATES - Primidone IMINOSTILBENE - Carbamazepine SUCCINIMIDE - Ethosuximide GABA transaminase inhibitor - Valproic

acid BENZODIAZEPINES -

Diazepam,Clonazepam, Lorazepam

CLASSIFICATION (Cont...) NEWER AGENTS GABA analogs -

Gabapentin ,vigabatrin OTHERS - Zonisamate,felbamate

PHENYTOIN PHARMACOLOGICAL ACTION CNS - Phenytoin has good anti

seizures activity and is one of the most effective drugs against generalized tonic-clonic seizures and partial seizures.

MECHANISM OF ACTION

Phenytoin

Blocks Na + Channels in Post Synaptic Neuron

Inhibits the action Potential of Neurons

ADVERSE EFFECTS Nausea, vomitting, epigastric pain Hypersensitivity Megaloblastic anemia Teratogenicity –when taken to the

pregnant lady ,it produce fetal hydantoin syndrome (Cleft Palate, Cleft lip & Microcephaly)

Hyperglycemia

USES 1. Generalized tonic clonic seizures and

partial seizures 2.Status epileptics –phenytoin is used by

slow IV Injection. 3.trigeminal neuralgia – as an

alternative to carbamazepine. 4.cardiac arrhythmias- phenytoin is

useful in digitalis induced arrhythmias.

Drug interaction Phenytoin is an enzyme inducer.

phenobarbitone competitively inhibit s phenytoin metabolism.

Carbamazepine and pheytoin enhances each others metabolism.

Valproate displace protein bound and may result in phenytoin toxicity.

Antacid absorption of phenytoin.

Fosphenytoin It is a prodrug of phenytoin that has

certain advantages over phenytoin for Parenterally use:

It is quickly converted to phenytoin in the body.

More potent. Less cardiotoxic. Safer on the intestine.

PHENOBARBITONE It has specific antiepileptic activity.

Primidone which is rarely used . Phenobarbitone is effective in tonic-clonic seizures and ineffective in absence of seizures.

MECHANISM OF ACTION Acts on the Synapse

Enhance the action of Inhibitory neurotransmitters (Eg. GABA)

Suppresses the excitatory neurotransmitters (Ach)

Opens Cl – ion Channels

Decreases the Seizures

Pharmacokinetics Oral Absorption

50 % bounds to plasma proteins

Metabolizes in liver

Excreted via urine

ADVERSE EFFECT Sedation Megaloblastic anemia Osteomalacia Ataxia Skin rashes USES Generalized tonic –clonic seizures Partial seizures

CARBAMAZEPINE Carbamazepine is a tricyclic compound Anti seizure activityIt has good Anti seizure activity .its

mechanism of action and anti epileptic action are similar to phenytoin.

Carbamazepine is also used in the treatment of trigeminal neuralgia

ADVERSE EFFECTS

Drowsiness Vertigo Nausea & Vomiting Ataxia

USES Generalized Tonic – Clonic Seizures Simple & Complex, Partial Seizures

Trigeminal Neurolgia

VALPORIC ACID MoA

Enhances the level of GABA (se Metabolism of GABA)

Blocks Na + Channels

Decreases low threshold Ca + current in thalamus

Reduce Seizure

ADVERSE EFFECTS

Sedation, Rashes, Ataxia and Tremors

USES Partial & Generalized Seizures

Useful particularly in Absence Seizures (Petit Mal Seizures)

Generalized Tonic Clonic Attacks

BENZODIAZEPINE

Diazepam is the drug of choice in status epilepticus.

Clonazepam is a potent anti epileptic drug useful in absence and myoclonic seizures.

Nitrazepam is used for treatment of myoclonic seizures.

NEWER ANTI EPILEPTICS

Gabapentin – It is a highly lipid soluble drug.

It crosses the BBB. Effective in tonic clonic seizure Exact MoA is unknown.

CHOICE OF ANTI SEIZURE DRUGS Simple / Partial Seizure – Carbamazepine,

Phenytoin, Valproic Acid Complex / Partial Seizure - Carbamazepine,

Phenytoin, Valproic Acid Partial with Secondarily Generalized -

Carbamazepine, Phenytoin, Valproic Acid Absence Seizures – Valproic Acid Tonic Clonic Seizure - Carbamazepine, Phenytoin,

Valproic Acid Tonic Clonic + Absence Seizure – Valproic Acid Myoclonic Seizures – Diazepam, Valproic Acid Status Epilepticus – Diazepam, Phenytoin, GA Febrile Convulsion - Diazepam