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Antiepileptic drugs


  • Seizure is a transient alteration of behavior due to the disordered, synchronous, and rhythmic firing of populations of brain neurons.
  • Epilepsy refers to a disorder of brain function characterized by the periodic and unpredictable occurrence of seizures.
  • Epileptic seizures have been classified into Partial Seizures, which begin focally in a cortical site, and Generalized Seizures, which involve both hemispheres widely from the outset.

Partial Seizures

Generalized Seizures

Simple Partial

Complex Partial

Partial seizures secondary Generalized

GTCS (Grand mal epilepsy, major epilepsy)

Absence seizures (Petit mal epilepsy, minor epilepsy)

Atonic seizures

Infantile Spasms (Hypsarrythmia)


Experimental models of Seizure induction in animals:

Maximal Electroshock Therapy


Phenylenetetrazole (PTZ) induction

Absence Seizures

Alumina Cream

Focal Seizures


Genesis Of Epilepsy






















  1. Older
    i. Phenytoin             
    ii. Carbamazepine                    
    iii. Sodium valproate        
    iv. Ethosuximide                        
    v. Phenobarbitone   
    vi. Primidone
  2. Newer
    i. Lamotrigine          
    ii. Vigabatrine          
    iii. Felbamate           
    iv. Topiramate
    v. Tiagabine             
    vi. Zonisamide         
    vii. Pregabalin          
    viii. Progabide
    ix. Gabapentin         
    x. Levtiracetam
  3. Latest Drugs
    i. Telampenal           
    ii. Lacosamide          

Individual Drugs

  1. Phenytoin
    1. MC used antiepileptic drug
    2. Na+ channel blocker
    3. Inhibits depolarisation shift
      1. Inhibits both origin & spread of seizure activity
      2. Maximally useful in MES seizure model (Maximum electroshock model)


  1. GTCS            
  2. Partial
  3. Posttraumatic epilepsy          
  4. Not effective in absence seizures


  1. Well absorbed orally; food may delay absorption
  2. 90% protein bound
  3. Pseudo-zero order kinetics
  4. Metabolized by hydroxylation
  5. Half life-15-30 hours
  6. Metabolism is inhibited by INH

Side effect

At Therapeutic Dose

At Toxic Dose

MC-gum hypertrophy-30%


Osteomalacia (decreases Vit-D/Calcium absorption, also induces metabolism)  

Megaloblastic anemia (Folic acid deficiency): increase in MCV (>100 Femt/Lit)h

Hodgkin like illness (paracortical hyperplasia)

Diagnostic confusion-in thyroid function tests


        i.      Decrease in release of insulin

Diplopia, nystagmus, ataxia (dose dependent)-occur in beginning

Sedation (high dose)

Cerebellar atrophy




Rare side effects

  1. ILD              
  2. PCRA            
  3. Gynecomastia

When to stop phenytoin therapy?

  1. Hypersenstivity reaction
  2. Put patient on carbamazepine or sodium valaproate

Fosphenytoin: more water soluble, hence better suited for i.v. use; as in Status epilepticus.


  1. Carbamazepine
    1. Iminostilbine derivative
    2. MOA-similar to phenytoin (Na+ channel block)
    3. TCAD analogue (tricyclic drug antidepressant)
      1. Overdose is medical emergency
      2. Rx-same as TCAD analogue


  1. Well absorbed; food increases absorption
  2. Auto-inducer
  3. Short acting
  4. Food increases absorption
  5. Metabolized to 10,11 epoxide---side effects  

Drug interactions

  1. OCP failure
  2. Phenytoin induced metabolism of valproate
  3. Valproate displaces phenytoin from protein binding sites
    1. Carbamazepine
    2. Sulfonamides


  1. Partial epilepsy (Temporal lobe epilepsy)
  2. Neuralgias (All types)
    1. Use gabapentin in refractory cases
    2. Bipolar disorders (maniac phase adjunct to antipsychotics)


  1. MC-rashes
  2. Hepatitis
  3. Neutropenia
  4. SIADH (Dilutional hyponatremia)
    1. Rx-demeclocycline


  1. Carbamezepine metabolism is inhibited by dextropropoxyphene---toxicity

Oxcarbezepine: Low Toxicity, Low Autoinduction, Low Hepatotoxicity, Low Interactions than carbamazepine.

More Hyponatremia (SIADH)                  

  1. Valproate sodium
    1. Carboxylic acid derivative
    2. Used as solvent for antiepileptic drugs
    3. Ionized drug; a/e activity is due to valproate ions
    4. Simple chemical structure


  1. Inhibit Na+ channel
  2. Inhibit Ca2+ T channel
  3. Inhibit NMDA receptor
  4. Block GABA uptake. 


  1. Well absorbed                              
  2. 90% protein bound      
  3. Metabolized by non CYP enzyme            
  4. Inhibitor of CYP enzymes

Drug interaction

  1. Valproate inhibits metabolism of clonazepam---status absence
  2. Inhibits metabolism of lamotrigine---toxicity of lamotrigine
  3. Valproate induces metabolism of carbamazepine---decreases its levels by 75%
  4. Phenytoin induces metabolism of valproate



  1. GTCS            
  2. Atonic          
  3. Akinetic        
  4. Myoclonic      
  5. Mixed                  
  6. Absence (Atypical)        
  7. Reflex epilepsy 

Side effects

a. MC-GI upset        
b. Weight gain         
c. Tremors       
d. Increase in liver enzymes

  1. Idiosyncratic hepatitis
    1. Develops in young babies
    2. More common in babies with L-carnitine deficiency
    3. Maximum incidence is at 4th month of introduction
    4. Avoided in young babies
  2. Alopecia followed by curly hairs
  3. Does not cause sedation like ethosuximide

Divalproex: Congener of Valproate.

  1. Ethosuximide
    1. Safe & long acting anticonvulsant          
    2. Blocks T currents in thalamus
    3. Protein bound                              
    4. Not metabolized
    5. Eliminated unchanged                  
    6. Avoided in renal failure


  1. GI upset
  2. Thrombocytopenia

Use: Only useful for absence seizure in children (now superseded by Valproate).

  1. Phenobarbitone
    1. Potent & long acting anticonvulsant
    2. GABAmimetic; oldest antiepileptic drug


  1. Well absorbed
  2. Protein bound
  3. Most potent enzyme inducer; even a single dose can induce liver enzymes (30 x)
  4. Not metabolized (only small part is oxidized)
  5. Avoided in renal failure
  6. 13gm is fatal dose


a. Epilepsy in children      
b. Epilepsy following febrile seizures
c. Hemolytic anemia

d. Neonatal jaundice        
e. Hypnotic-sedative withdrawal  



  1. Obstructive sleep apnea (OSA) (Alprazolam is sedative-hypnotic of choice)
  2. Metabolic acidosis
  3. Cardio-pulmonary disorders
  4. COPD
  5. Asthma
  6. Acute intermittent porphyria


  • Converted in liver to Phenobarbitone and PEMA.
  • Less effective but similar toxicity.
  • Not much used.

Newer anti epileptic drugs

  • General properties

a. Less potent  
b. Less effective                               
c. More expensive    

d. More toxic                    
e. Mainly used in partial epilepsies          
f. Used as “add on” drugs


Newer drugs

  1. Lamotrigine
    1. Na+ channel blocker
    2. Used as montherapy in GTCS, partial seizure
    3. Major anticonvulsant
    4. Rashes & hypersensitivity reactions like SJ syndrome are S/E.
    5. Mood stabilizer, anti-neuropathic
    6. Increasingly used in all types of epilepsy like valproate
    7. Also in Bipolar disorder
    8. In neuropathic pain
  2. Vigabatrin
    1. GABA-Transaminase inhibitor
    2. Used in infantile spasm (ONLY IN REFRACTORY CASES)
    3. DOC-ACTH
    4. S/e- Spinal cord edema, visual hallucinations
  3. Topiramate
    1. Carbonic anhydrase inhibitor & also Ca2+ T channel inhibitor and kainite receptor blocker.
    2. Used in:
      1. Drug refractory migraine
      2. Migraine with epilepsy
      3. Obesity with migraine/obesity with epilepsy
      4. Prolonged use causes weight loss
      5. Also used for drug induced weight again
      6. Has good alcohol anticraving activity
  • DOC for alcohol anticraving activity is Acamproste
  • SSRIs are also used
  • Naltrexone can reduce the relapse
  1. S/e-HSP (Hypersensitivity, stone, paresthesia)
  1. Tiagabine
  1. Inhibits GABA uptake by neurons ( inhibit GAT-1)
  2. GABAergic drug
  3. Used in partial epilepsy
  1. Zonisamide
  1. Sulfonamide drug
  2. Sulpha allergy can occur 
  1. Pregabalin, Progabide, Gabapentin 
  1. Act upon alpha2 delta receptors
  2. These are “anti-neuropathic”
  3. Anti-neuralgia
  4. No drug interactions
  6. Heavy sedation
  7. Weight gain occurs 


6 BZDs are used in epilepsy



Given intravenously or rectally is highly effective for stopping continuous seizure activity, especially Generalized tonic-clonic, Status epilepticus, Infantile spasms.

The drug is occasionally given orally on a long-term basis, although it is not considered very effective in this application, probably because of the rapid development of tolerance.

A rectal gel is available for refractory patients who need acute control of bouts of seizure activity.


More effective and longer acting than diazepam in the treatment of status epilepticus


Infantile spasms and myoclonic seizures.


Long acting drug against Absence Seizures.

It is one of the most potent anti-seizure agents known.

It is also effective in some cases of myoclonic seizures and has been tried in infantile spasms.

Sedation is prominent, especially on initiation of therapy


An adjunct to treatment of complex partial seizures in adults.


Widely used in a variety of seizure types

Less sedative potential than benzodiazepines


Latest antiepileptics:

  1. Talampenal
    1. AMPA antagonist
  2. Lacosamide     
    1. Na+ channel blocker
    2. CRMP modulator responsible for formation of abnormal neuronal connections in epilepsy.
  3. Stiripentol
    1. Barbiturate like action
    2. Refractory generalized tonic-clonic seizures in patients with Severe Myoclonic Epilepsy of Infancy (SMEI),      Dravet’s syndrome)
  4. Rufinamide
    1. Na+ channel blocker
    2. All are useful for LENNOX-GESTAUT SYNDROME
  5. Retigabine (Ezogabine)
    1. K+ channel facilitator – unique mechanism
    2. Approved as an adjunct in Partial seizures
    3. S/E- blurred vision, confusion, Bladder dysfunction 
  6. Felbamate
    1. ‘Orphan’ drug              
    2. Na+ blocker        
    3. Anti-glutamate            
    4. Use-Lennox-Gestaut syndrome


  1. Hepatitis                      
  2. Neutropenia                
  3. Aplastic anemia

Drugs With Antiepileptic Property But Not Used

  1. Trimethadione:
  • First antiepileptic ,
  • Used in absence seizures ,
  • Now superseded by other drugs
  1. Acetazolamide:
  • Relatively less effective
  1. Sulthiame:
  • Another carbonic anhydrase inhibitor,
  • Not approved by USA-FDA

Choice Of Drugs For The Therapy Of The Epilepsies

Partial Seizures

Secondary Gtcs

1 Line: Carbamazepine, Phenytoin

2 Line: Valproate (Doc- Sec. Gen), Phenobarbitone

Alternative 1 Line: Gabapentin, Lamotrigine, Topiramate

Absence Seizures

1 Line: Valproate, Ethosuximide

Alternative: Lamotriginine (Not Approved)

Myoclonic Seizures

Valproate (Doc)

Zonisamide, Levetiracetam

Febrile Convulsions

Rectal Diazepam

Infantile Spasms

Glucocorticoids, Benzodiazepines, Vigabatrin

Lennox-Gastaut Syndrome

Lamotrigine, Topiramate

Epilepsy In Pregnancy

Based On Choice, Risk Vs Benefit

No Definitive. (Oxcarbazepine Can Be Used, Earlier Phenobarbitone)

Juvenile Myoclonic Epilepsy

Valproate (Doc)

Lamotrigine, Topiarmate

(Contraindicated- Phenytoin, Carbamazepine)


Status Epilepticus

  • There are many forms of status epilepticus. The most common, generalized tonic-clonic status epilepticus, is a life-threatening emergency, requiring immediate cardiovascular, respiratory, and metabolic management as well as pharmacologic therapy. The latter virtually always requires intravenous administration of antiseizure medications.




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