Antiepileptics

Antiepileptics

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  ANTIEPILEPTIC S
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  DEFINITION  Epilepsy  Epilepsyis 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.
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  SEIZURE TYPES
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  CLASSIFICATION OF ANTIEPILEPTICS  HYDANTOINS-Phenytoin,Mephenytoin  BARBITURATES- Phenobarbotone, Mephobarbitone  DEOXYBARBITURATES - Primidone  IMINOSTILBENE - Carbamazepine  SUCCINIMIDE - Ethosuximide  GABA transaminase inhibitor - Valproic acid  BENZODIAZEPINES - Diazepam,Clonazepam, Lorazepam
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  CLASSIFICATION (Cont...)  NEWERAGENTS  GABA analogs - Gabapentin ,vigabatrin  OTHERS - Zonisamate,felbamate
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  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.
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  MECHANISM OF ACTION
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  Phenytoin Blocks Na +Channels in Post Synaptic Neuron Inhibits the action Potential of Neurons
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  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
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  USES  1. Generalizedtonic 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.
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  Drug interaction  Phenytoinis 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.
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  Fosphenytoin  It isa 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.
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  PHENOBARBITONE  It hasspecific antiepileptic activity. Primidone which is rarely used . Phenobarbitone is effective in tonic- clonic seizures and ineffective in absence of seizures.
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  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
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  Pharmacokinetics  Oral Absorption 50 % bounds to plasma proteins  Metabolizes in liver  Excreted via urine
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  ADVERSE EFFECT  Sedation Megaloblastic anemia  Osteomalacia  Ataxia  Skin rashes  USES  Generalized tonic –clonic seizures  Partial seizures
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  CARBAMAZEPINE  Carbamazepine isa tricyclic compound  Anti seizure activity It 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
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  ADVERSE EFFECTS  Drowsiness Vertigo  Nausea & Vomiting  Ataxia  USES  Generalized Tonic – Clonic Seizures  Simple & Complex, Partial Seizures  Trigeminal Neurolgia
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  VALPORIC ACID MoA Enhances the level of GABA (↓se Metabolism of GABA)  Blocks Na + Channels  Decreases low threshold Ca + current in thalamus  Reduce Seizure
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  ADVERSE EFFECTS  Sedation,Rashes, Ataxia and Tremors USES  Partial & Generalized Seizures  Useful particularly in Absence Seizures (Petit Mal Seizures)  Generalized Tonic Clonic Attacks
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  BENZODIAZEPINE  Diazepam isthe 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.
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  NEWER ANTI EPILEPTICS  Gabapentin– It is a highly lipid soluble drug.  It crosses the BBB.  Effective in tonic clonic seizure  Exact MoA is unknown.
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  CHOICE OF ANTISEIZURE 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