antiepileptic drugs

• Epilepsy


  A group of chronic CNS function disorders characterized by recurrent seizures
• Seizures


  Sudden, transitory, and uncontrolled episodes of brain dysfunction resulting from abnormal discharge of neuronal cells with associated motor, sensory or behavioral changes
• According to WHO statistics, the current world, about 50 million people with epilepsy, 80% of them in developing countries. Every year, 2 million new patients with epilepsy. Although the standard the onset of treatment to 80% of patients under control, but there are still hundreds of thousands of patients (there are 0.5 million people in the United States only) have no control.
• Epilepsy


  • The sudden attack local brain lesions neurons abnormal high frequency discharge and spread to the surrounding tissue, then transient brain dysfunction appeared
  • A sudden onset of short movement, feeling, consciousness, spirit and plant nerve dysfunction, may be accompanied by electroencephalogram (ecg) changes, with the characteristics of sudden onset, recurrent and short
  • Medication for a long time, to reduce or prevent attacks, but cannot reach a radical cure
• Causes of Secondary Epilepsy

  • Trauma
  • Encephalitis
  • Drugs
  • Birth trauma
  • Withdrawal from depressants
  • Tumor
  • High fever
  • Hypoglycemia
  • Extreme acidosis
  • Extreme alkalosis
  • Hyponatremia
  • Hypocalcemia
  • Idiopathic
• Pathophysiology of Seizures


  1. Brain local lesion depolarizes together

  2. Produce high-frequency, out-break discharge

  3. Spread to surrounding normal tissue

  4. Interfere with normal neuron electric activity

  5. The brain transient dysfunction
• Classification of Epilepsy


  • Partial Seizures
  • Generalized Seizures
• Simple Partial Seizures


  • Occur at any age
  • The patient does not lose consciousness
  • Abnormal activity of a single limb or muscle group
  • There may be also sensory symptoms
• Complex Partial Seizures

  • Impairment or loss of consciousness
  • Sensory hallucinations (smell or taste)
  • Motor dysfunction (automatism) e.g. chewing movements, lip smacking, postictal confusion
  • Speech disturbances (if dominant hemisphere)
• Types of Generalized Seizures

  • Absence Seizures (petit mal epilepsy)
  • Status epilepticus
  • Myoclonic Seizures
  • Febrile seizures
• Absence Seizures (petit mal epilepsy)

  • Occur mainly in children till puberty or beyond
  • Brief abrupt loss of consciousness
  • Staring, rapid eye blinking for few seconds with impaired awareness then return to full function
  • Characteristic EEG pattern
• Status epilepticus

  • Two or more seizures lasting for a total of 30 minutes or longer without recovery of full consciousness between them
  • Life threatening and requires emergency treatment
• Myoclonic seizures

  • Sudden brief involuntary muscle contractions (shock---like jerks of trunk, neck & limbs)
  • Occur at any age usually around puberty or early adulthood
  • Consciousness is not impaired
• Febrile seizures

  • They occur in young children with illness accompanied by high fever
  • Seizures consist of tonic-clonic convulsions
• 1912: Phenobarbital

  1938: Phenytoin continue to be applied today

  1964: Sodium Valproate
• Though many new drugs have been synthesized in the past 60 years, the drugs effect remain in symptomatic treatment level.
• Principles of Using Antiepileptic Drugs

  • Initially we use 1st line drug (monotherapy) until seizures are controlled or toxicity occurs
  • If 1st line drug is ineffective, switch to another drug or add a 2nd line drug (Combination Therapy)
  • Antiepileptic therapy must be continued for at least 2 years after the last attack, then the drug should be stopped gradually
• Mechanism of Antiepileptic drugs

  • Inhibite the excessive discharge of neuron
  • Curb the spread of abnormal discharge
• Mechanism 1: Decreased excitability input

  • Reducing electrical excitability of cell membranes, through inhibition of sodium channel
  • A few drugs appear to act by a mechanism, namely inhibition of T-type calcium channels
• Mechanism 2: Increased inhibitory (GABA) input

  Enhancing GABA-mediated synaptic inhibition. This may be achieved by an enhanced pre- or post-synaptic action of GABA, by inhibiting GABA-transaminase, or by drugs with direct GABA-agonist properties
• The Primary Antiepileptic Drugs

  • Phenytoin Sodium
  • Phenobarbital
  • Carbamazepine
  • Ethosuximide
  • Sodium Valproate
  • Benzodiazepine
• Phenytoin Sodium

  • Well absorbed when given orally, however, it is also available as iv. (for emergency)
  • 80-90% protein bound
  • Induces liver enzymes (very important)
  • Metabolized by the liver
  • Excreted in urine
  • Plasma t ½ approx. 20 hours
  • Therapeutic plasma concentration 10-20 µg/ml (narrow), dose 300-400mg/day
• Mechanism of Action of Phenytoin Sodium

  • Membrane stabilization by blocking Na & Ca influx into the neuronal axon
  • Inhibits the release of excitatory amino acids via inhibition of Ca influx
• Therapeutic Uses of Phenytoin Sodium

  • Generalized tonic-clonic seizures & partial seizures (Be the first choice!)
  • Prosopalgia
  • Ventricular and ventricular arrhythmias induced by Digoxin
• Adverse Reactions of Phenytoin Sodium

  • Gastrointestinal tract (G.I.T): nausea, vomiting, anorexia
  • Neurological like ataxia, headache, vertigo, diplopia, nystagmus
  • Sedation
  • Gingival hyperplasia
• Phenytoin Sodium can pass through the placental barrier, so lactating women should stop breastfeeding
• To monitor blood routine, liver function, blood calcium, blood pressure, plasma concentration (especially in child)

  The nervous system response is related to dose:

  >20 µg/mL : ataxia

  >40 µg/mL : mental disorder

  >50 µg/mL : coma
• Symptoms of cal like ataxia

  • headache
  • vertigo
  • diplopia
  • nystagmus
• Phenytoin Sodium is a Primary Antiepileptic Drug
• Gingival hyperplasia

  • It common occurs in children and teenagers after long term use
  • This effect can resolve after drug withdrawing for 3~6 months
• Observing after treatment with Phenytoin Sodium

  Stop using immediately when the patient can not tolerate or have an allergic reaction
• Monitoring with Phenytoin Sodium

  1. Blood routine

  2. Liver function

  3. Blood calcium

  4. Blood pressure

  5. Plasma concentration (especially in child)
• Nervous system response to Phenytoin Sodium

  • >20 µg/mL: ataxia
  • >40 µg/mL: mental disorder
  • >50 µg/mL: coma
• Mechanism of Action of Phenytoin Sodium

  • Increases the inhibitory neurotransmitters (e.g: GABA) and decrease the excitatory transmission
  • Prolongs the opening of Cl- channels
• Phenobarbital is a Primary Antiepileptic Drug
• Therapeutic use of Phenobarbital

  • All types of epilepsy. The effects by turns are: grand mal and status epileptics＞partial psychomotor seizure＞petit mal
  • It is not the first choice drug for CNS inhibition
• Phenobarbital can lead to low prothrombin and bleeding in Neonatals
• Monitoring with Phenobarbital

  1. Blood routine

  2. Liver function

  3. Blood calcium

  4. Blood pressure

  5. Plasma concentration (especially in child)
• Observing after treatment with Phenobarbital

  Stop using immediately when the patient can not tolerate or have an allergic reaction
• Both Phenobarbital and Phenytoin are liver drug metabolizing enzyme inducers, so they can accelerate a variety of drugs and reduced efficacy