An Overview on Anti-epileptic Drugs

Introduction to An Overview on Anti-epileptic Drugs,
Introduction to Epilepsy, Types of Seizures, Classification, Mechanism of Action, Pharmacokinetics, Uses, Adverse Effects, Contraindications, New Drugs
Presented by
A. Harsha Vardan Naidu
Department of Pharmacology

1. 1 A seminar as a part of curricular requirement for I year M. Pharm I semester Presented by A. Harsha Vardan Naidu (20L81S0107) M. Pharmacy Department of Pharmacology Under the guidance of Mr. A. Sudheer kumar , M. Pharm. Associate Professor, Department of Pharmacology. An Overview on Anti-epileptic Drugs

2. 2 Introduction to Epilepsy Types of Seizures Classification Mechanism of Action Pharmacokinetics Uses Adverse Effects Contraindications New Drugs References Contents

3. 3 Convulsion is a condition in which muscles contract and relax quickly and cause uncontrolled shaking of the body.  Seizure  is a change in electrical activity between neurons that causes temporary abnormalities in muscle tone or movements (stiffness, twitching), behaviours, sensations or states of awareness. Epilepsy  is a neurological disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behaviour, sensations, and sometimes loss of awareness. A seizure is a single occurrence, whereas epilepsy is a neurological condition characterized by two or more unprovoked seizures. Introduction

4. 4 Brain conditions including stroke or a tumour Genetical problem Head trauma, from a vehicle accident Drug abuse or alcohol misuse Infectious diseases like viral encephalitis Lack of oxygen during birth Prenatal injury- brain damage that occurs before child birth COVID-19 infection Blood vessel malformations Causes of Epilepsy:

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6. 6 Stages of seizures

7. 7 Partial seizures - Simple partial seizure - Complex partial seizure - Partial with secondarily generalised seizure Generalized seizures - Tonic clonic / grandmal seizure - Clonic seizure - Tonic seizure - Atonic seizure - Myoclonic seizure - Absence/ Petit mal seizure Non epileptic seizure- not related to epilepsy, occurs due to diabetes/ high fever. Status epilepticus - condition where seizure lasts for more than 5 mins . Types of seizures

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9. 9 Managing seizures

10. 10 Hydantoins : Phenytoin, Mephentoin Barbiturates: Phenobarbitone , Mephobarbitone Deoxy barbiturate: Primidone Benzodiazepines: Diazepam, Clonazepam , Lorazepam Iminostilbenes : Carbamazepine Succinimides : Ethosuximide GABA transaminase inhibitors: Valproic acid, Vigabatrin GABA analogs : Gabapentin , Pregabalin Others: Lamotrigine , Levetiracetam Classification

11. 11 Conduction of nerve impulse

12. 12 Mechanism of action

13. 13 Phenytoin First line drug for partial seizures. Inhibits Na+ channels. Prodrug - Fosphenytoin for IM/IV administration. High plasma protein binding. Adverse effects: CNS sedation ( drowsiness, ataxia, confusion, insomnia, nystagmus ), gum hyperplasia, hirsutism . Carbamazepine First line drug for partial seizures. Inhibits Na+ channels. Adverse effects- CNS sedation, agranulocytosis and aplastic anaemia in elderly patients, leukopenia .

14. 14 Phenobarbital Used for partial seizures, effective in neonates. S econd line drug in adults due to severe CNS sedation. Allosteric modulator of GABA-A receptor (increase open time). Adverse effects- CNS sedation but produces excitation in some patients. Skin rashes if allergic. Tolerance and dependence may be possible. Primidone Used for partial seizures . Allosteric modulator of GABA-A receptor (increase open time ). Not highly bound to plasma. Adverse effects- CNS sedation.

15. 15 Benzodiazepines Eg - Diazepam, Clonazepam . Used to treat status epilepticus . Allosteric modulators of GABA-A receptor- increase frequency. Adverse effects- CNS sedation, paradoxical hyper excitability in children, tolerance and dependence. Valproate Used for partial seizures, first line drug for generalized seizures. Enhance GABA transmission, block Na+ channels, activates K+ channels. Adverse effects- CNS depression, anorexia, nausea, vomiting, hair loss, weight gain, may cause birth defects.

16. 16 Ethosuximide Used for absence seizures. Blocks T-type Ca++ currents in thalamus. Adverese effects- gastric distress, pain, nausea, vomiting. Less CNS side effects than other anti-epileptic drugs, transient fatigue, dizziness, headache. Oxcarbamazepine Approved for add-on therapy, monotherapy for partial seizures, that are refractory to other antiepileptic drugs. Activity dependent blockade of Na+ channels, also open K+ channels. Similar to carbamazepine , it causes CNS sedation, but may be less toxic.

17. 17 Gabapentin Add-on therapy for partial seizures. Also effective as monotherapy . Interfere with GABA uptake. Adverse effects- less CNS sedative than other classic anti-epileptic drugs. Lamotrigine Add-on therapy and monotherapy for refractive partial seizures. Effective against generalized seizures. Inhibition of Na+ channels, inhibition of glutamate release, may inhibit Ca++ channels. Less CNS sedative than other anti-epileptic drugs, dermatitis.

18. 18 Tiagabine Add- on therapy for partial seizures. Interferes with GABA reuptake. CNS sedative Minimal drug interaction. Zonisamide Add- on therapy for partial and generalized seizures. Blocks Na+ channels and T- type Ca++ channels. Causes CNS sedation.

19. 19 Felbamate Third-line drug for refractory partial seizures. Frequency dependent- inhibition of Na+ channels, modulation of NMDA receptors. Aplastic anaemia and severe hepatits reduces its use. Levetiracitam Add- on therapy for partial seizures. Binds to synaptical vessicle protein SV2A, may regulate neurotransmitter release. Causes CNS ddepression .

20. 20 Good absorption from gut, with a bioavailability of 80- 100%. They show minimal plasma protein binding( except phenytoin , valproic acid). Half life is usually 12- 24 hours and it increases upto 60 hours when plasma concentration of drug increases. Metabolised in liver by non-CYP450 isoenzymes . Enzyme inducers- Phenytoin, Phenobarbital. Enzyme inhibitors- Valproate , Topiramate . Primarily cleared renally . Pharmacokinetic profile

21. 21 Used to treat partial, generalized and mixed seizures. Used to treat Status epilepticus Used as prophylaxis in case of tumours in brain. Manic depressive illness and acute mania Phenytoin is a group 1B anti-arrhythmic agent. Several drugs, especially carbamazepine and lamotrigine , are useful for bipolar disorder. Many drugs are useful in migraine, e.g., phenytoin , gabapentin , topiramate . Uses of Antiepileptic Drugs

22. 22 Hypersensitivity reactions like rashes, photosensitivity, hepatitis Vomiting, diarrhoea, weight loss, tremors At high plasma levels- ataxia, vertigo, nystagmus , drowsiness Gum hypertrophy Aplastic anaemia Foetal hydantoin syndrome Osteoporosis Teratogenesis Neuropathy, coma Epigastric pain, hypotension, arrythmias Adverse effects

23. 23 Contraindications Cardiac patients Pregnant women Patients with livers disorder People with lung infections etc Latest discovery Levitiracitam Brivaracetam Cannabidiol Stiripentol

24. 24 Padmaja Udaykumar . Pharmacology for Dental and Allied Health Sciences. 2017; 4 th edition. Tripathi , K. D. Essentials of Medical Pharmacology. 2013. JP Medical Ltd. Christopher Melinosky . Epilepsy drugs used to treat seizures. WebMD. 2020. Marketa Mavanova . Pharmacokinetic characteristics of antiepileptic drugs. NCBI. 2016; 6(1): 8-20. References

25. 25 THANK YOU