Antipileptic drug

epilepsy, their classification, antiepileptic drug, their mechanisam and pharmacology

1. Pharmacology of antiepileptic drug Presented by Miss. Ashvini Govande Assistant Professor Kandhar College of Pharmacy, Kandhar

2. Content What is epilepsy Classification of epilepsy Mechanism of action of epilepsy Antiepileptic drug classification Mechanism of action of antiepileptic drug Pharmacology of drug

3. What is Epilepsy Epilepsy  is a central nervous system (neurological) disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness. Epilepsy is also known as epileptic seizures or convulsions .

4. Classification OF Seizure

5. Mechanism of action of epilepsy

6. Antiepileptic drug Antiepileptic are a class of drugs that try and prevent rapid, repitative , stimulation of brain that causes seizures activity. Mechanism of action of Antiepileptic drug – Enhancement of GABA action Inhibition of sodium channel function Inhibition of calcium channel function Other mechanisam include- Inhibition of glutamate release Block of glutamate receptor

7. Classification Category Drug Barbiturates Phenobarbitone Deoxybarbiturate Primidone Hydantoin Phenytoin , Fosphenytoin Iminostilbene Carbamazepine , Oxcarbazepine Succinamide Ethosuximide Aliphatic carboxylic acid Valproic acid Benzodiazepines Clonazepam , Diazepam, Lorazepam Phenyltriazine Lamotrigine Cyclic GABA analogue GABA pentine Newer drugs Vigabatrine , Zonisamide , Topiramate , Tiagabine , Levetiracetam

8. Mechanism of action of Antiepileptic drug

9. Phenobarbitone Barbituric acid derivatives MOA- It act on GABA receptors Phenobarbital increases the flow of chloride ions into the neuron which decreases the excitability of the post-synaptic neuron. Uses- Anticonvulsant Sedative hypnotic p roperties

10. Primidone Primidone has anticonvulsant activity due to its two metabolite 1) Phenobarbital 2) Phenylethylmalonamide (PEMA) MOA- It  interactions with voltage-gated sodium channels which inhibit high-frequency repetitive firing of action potentials. It also increases GABA-mediated chloride flux

11. Continue... Adverse effect – Sluggishness, Incoordination , Difficulty in thinking, Slowness of speech, Faulty judgement, Drowsiness or coma, Shallow breathing, Staggering, Severe cases coma and deth . Uses- Used as anticonvulsant to control grand mal, psychomotor and focal epileptic seizures. First-line therapy for essential tremor along with  propranolol

12. Phenytoin MOA- They blocks sodium channel Which reduces hyperexcitability of post synaptic membrane. Uses- Anticonvulsant Anti-arrhythmic Muscle relaxant

13. Continue... Pharmacokinetic- Absorption- Well absorbed orally Bioavailbility is 85% Food influences absorption Distribution- Vol. Of distribution 0.5-1.0L/kg Protein binding- 90% Metabolism- Hydroxylated in liver by saturable enzyme system Elimination- Drug is excreted in bile as inactive metabolite which are then reabsorbed from the intestine and excreted through urine

14. Continue... Adverse effect- Rash Gum hypertrophy Ataxia Nystagmus Slurred speech Confusion Drug induced lupus Agranulocytosis Aplastic anemia Hepatitis and anticonvulsant hypersensitivity syndrome

15. Carbamazepine MOA- Carbamazepine is a sodium channel blocker It binds preferentially to voltage-gated sodium channels in their inactive conformation, which prevents repetitive and sustained firing of an action potential. Uses- Used to treat partial seizures, tonic- clonic seizures, Trigeminal neuralgia Psychiatric disorder such as- manic depressive illness and aggression due to dementia. Anticholinergic , Central antidiuretic , antiarrhythmic , muscle relaxant, antidepressant, sedative and neuromuscular blocking proprty .

16. Continue... Adverse effect- Dizziness, Drowsiness, Unsteadiness, Nausea and Vomiting. Aplastic anemia , Agranulocytosis , Pancytopenia , Bone marrow depression, Thrombocytopenia, Leukopenia,Leukocytosis , Eosinopihlia , Acute intermitent porphyria . Contraindication- Not used in patient with a history of Bone marrow depression, Hypersensitivity. Drug interaction- with lithium increases risk of neurotoxicity.

17. Ethosuximide MOA- It blocks the calcium channel Uses- Absence seizures. Adverse effect- Tiredness, Headache, Gastrointestinal intolerance, Mood channges , Agitaion , Drowsiness, Inability to concentrate, Hypersensitivity .

18. Valproic acid MOA- By blocking the excitary glutamate receptor By inhibiting GABA metabolism. Uses- Absence seizures Mania and bipolar illness Myoclonic and atonic seizures Adverse effect- Anorexia, Vomiting, Heart burn, Drowsiness, Ataxia, Tremor, Alopecia, Curling of hair, increased bleeding tendency, Rashes, Thrombocytopenia

19. Benzodiazepines MOA- It potantiate the effect of GABA GABA is an inhibitory neurotransmitter. Uses- Clonazepam is used to treat Myotonic and atonic seizures, Photosensitive epilepsy, absence seizures, Lennox- Gastaut syndrome, Akinetic and myoclonic seizures. Lorazepam is used to treat anxiety, status epilapticus , sedation, anterograde amnesia.

20. Lamotrigine MOA- It resembles the action of phenytoin and carbamazepine in inhibiting voltage sensetive sodium channel and stabilize membrane. Uses- Partial seizures, Tonic clonic seizures, Lennox- Gastaut syndrome

21. GABA pentine MOA- It increases synaptic concentration of GABA Enhances GABA response Reduces the release of mono-amine neurotransmitters. Uses- Postherpetic neuralgia Partial seizures

22. Vigabatrine MOA- Inhibitor of GABA- transaminase which degrades GABA Uses- Partial seizures with or without generalization. Adverse effect- Behavioural changes, Depression and Psychosis, Drowsiness, Anemia Motor disturbance.