Anti Epileptic Drugs

Anti Epileptic Drugs

Introduction

  • Epilepsy is the condition characterized by Recurrent episodes of seizures
  • Seizures result from Episodic electrical discharges in cerebral neurons associated with prolonged depolarization during which sustained, high frequency repetitive firing occurs, followed by prolonged hyperpolarization.
  • Goal of Drug is to Restore Normal Patterns of Electrical activity

Epilepsies classification

1. Generalized seizures

A. Generalized Tonic- Clonic seizures

  • Major Epilepsy
  • Commonest
  • Last for 1-2 mins
  • Unconsciousness & Tonic Spasm followed by clonic jerking & depression of all CNS function

B. Absence Seizures

  • Minor Epilepsy
  • Last for 1/2 min
  • Momentary Loss of consciousness & patient freezes and stares in one direction.
  • Little / no bilateral jerking.

C. Atonic Seizures

  • Akinetic Epilepsy
  • Unconsciousness with relaxation of all muscles.

D. Myoclonic Seizure

  • Shock like momentary contraction of a single muscle.

E. Infantile spasms

  • In infants
  • Most typical epilepsy
  • Muscle spasm
  • Progressive Mental Deterioration
2. Partial Seizures

A. Simple Partial Seizure

  • Cortical focal Epilepsy
  • Lasts for 1/2 to 1 min
  • No loss of consciousness
  • Convulsions are confined to a particular area of cortex

B. Complex Partial Seizure

  • Temporal lobe epilepsy
  • Attacks of Bizarre & confused behaviors
  • Emotional changes
  • Purposeless movements
  • Lasts for 1-2 min
  • Aura (feeling & Seizures) often precedes

C. Simple Partial / Complex Partial Seizure Secondarily Generalized

  • Partial Seizure occurs first and evolves into Generalized Tonic-clonic with loss of consciousness

Drug Classification

 

Mechanism of Action

These drugs act via various mechanisms –

  • Decreased axonal conduction by preventing Na+ influx through fast Na+ channels – Carbamazepine, Phenytoin
  • Increased inhibitory tone by facilitation of GABA mediated hyperpolarization- Barbiturates, BZDs
  • Decreased excitatory effects of glutamic acid – Lamotrigine, Topiramate (blocks AMPA Receptors), Felbamate ( blocks NMDA Receptors)
  • Decreased Presynaptic Ca2+ influx through type-T channels in thalamic neurons – Valproic acid & Ethosuximide

Important Antiepileptic Drugs

1. Phenytoin

Mechanism –

Blocks axonal voltage gated Na+ channels → Prevents seizure propagation

Pharmocokinetics –

  • Variable absorption
  • Nonlinear Kinetics
  • Induction of cytochrome P450
  • Zero-order Kinetics

Uses –

  • GTCS
  • Partial Seizures
  • Status Epilepticus
  • Trigeminal Neuralgia (Non Epileptic Use)

Side Effects –

  • CNS Depression
  • Hirsutism
  • Osteomalacia
  • Gingival Hyperplasia
  • Megaloblastic Anemia
  • Hypersensitivity/ Allergy

Contraindications –

  •  Myoclonic Seizure
  • Absence Seizures
2. Carbamazepine

Mechanism –

Blocks axonal voltage gated Na+ channels → Prevents seizure propagation.

Uses –

  • GTCS
  • Partial Seizures [DOC]
  • Trigeminal Neuralgia [DOC]
  • Mania & Bipolar Disorder
  • Diabetes Insipidus

Pharmacokinetics –

  • Induces cyctochrome P450

Side effects –

  • CNS Depression
  • Osteomalacia
  • Megaloblastic Anemia
  • Aplastic Anemia
  • Exfoliative Dermatitis.
  • Increased ADH Secretion (Dilutional hyponatremia)
  • Cleft Lip & Palate
  • Spina bifida (if given to pregnant mother)
  • Hepatotoxic
  • Allergy (Steven Jenson’s Syndrome/ Toxic Epidermal Necrolysis)

Contraindications –

  • Myoclonic seizures
  • Atonic Seizure
  • Absence Seizures
3. Valproic Acid

Enzyme inhibitor

Mechanism –

  • Blocks axonal voltage gated Na+ channels → Prevents seizure propagation.
  • But also inhibition of GABA Transaminase (increases GABA levels)
  • Blockade of T-Type Ca2+ channels
  • Decreases Glutamate levels

Uses –

  • GTCS
  • Absence Seizures
  • Myoclonic Seizure
  • Dravet Syndrome
  • Tardin Dyskinesia
  • Mania & Bipolar Disorder
  • Migraine Prophylaxes
  • Status Epilepticus (Used iV)

Pharmacokinetic –

Inhibits cytochrome P450

Side Effects –

(MNEMONIC – VALPROATE)

V = Vomiting, Nausea (most common)

A = Alopecia, curling of hairs

L = Liver toxicity

P = Pancreatitis

R = Rashes

O = Obesity

A = increased Ammonia

T = Teratogenic (causes Neural Tube Defects), Thrombocytopenia

E = Enzyme inhibitor

4. Ethosuximide

Mechanism –

Blockade of T-type Ca2+ channels in Thalamic neurons

Uses

  • Absence Seizures
  • Ethosuximide is drug of choice in children(<2yrs)

Other Ant seizure Drugs

1. Lamotrigine
  • Blocks Na+ channels & Glutamate Receptors
  • Also T type CCB
  • Used in Various Seizures
  • Side effects – Stevens – Johnson Syndrome (Rashes)
  • These are safer in pregnancy [NOT TERATOGENIC]
2. Levetiractam :
  • Mechanism – SV2A inhibitor
  • Used in focal Onset & Generalized Tonic-clonic seizures.
  • Safe in pregnancy
3. Topiramate
  • Block Na+ channels and glutamate Receptors (AMPA blocker)
  • Enhances GABA Activity.
  • Also mild carbonic Anhydrase inhibitor

Uses –

  • In focal seizures in adults & children > 2 years.
  • Migraine prophylaxis
  • Decreasing craving in Alcoholics
  • Obesity
4. Felbamate
  • Blocks Na+ channels and glutamate receptors (NMDA blocker)
  • Used in Partial Seizure
  • Side effects is Aplastic Anemia.
5. Gabapentin
  • Affect Ca 2+ channels.

Uses –

  • Seizure states
  • Neuropathic Pain
  • Post herpetic neuralgia

Side effect – Sedation

6. Zonisamfde
  • Na+ channel blocker, T type Ca2+ Channel blocker
  • Also Carbonic Anhydrase inhibitor
  • Used in Seizure states
  • Side effect is Renal Stone formation
7. Locasamide
  • Na+ channel blocker
  • CRMP2 Protein inhibitor
8. Vigabatrin
  • Inhibits Transaminase
  • Used in treatment of infantile spasms with Tuberous Sclerosis
  • Side effect is leads to Visual impairment
9. Ezogabine
  • K+ channel opener
  • Used to treat Partial Seizure
10. Barbiturates & Benzodiazepams

They block the GABA receptor

Example –

  • Clonazepam – Absence Seizures
  • Lorazepam – Status Epilepticus
  • Carbamazepine – Partial Seizure etc.

FINAL SUMMARY

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