Anti-Epileptic Drugs (AEDs)

Mechanism of action

 Enhancement of GABA action.

 Blocking voltage-gated channels of sodium Na+ and Calcium Ca2+.

 Interfering with excitatory glutamate transmission.

 AEDs suppress seizures but do not “cure” or “prevent” epilepsy.

Classification of AEDs

First - Generation AEDs

Phenytoin- PHT (1940)

Pharmacokinetics

 Well absorbed when given orally, however, available as IV for emergency.

 80-90% protein bound.

Mechanism of action

 Membrane stabilization by blocking Na and Ca influx into the neuronal axon.

 Inhibits the release of excitatory amino acids via inhibition of Ca influx.

Indications

 Major first-line AED in the treatment of partial and secondarily generalized seizures.

Adverse effects

Dose Related

 Upset G.I.T
  Neurological conditions like headache, vertigo, ataxia (abnormal, uncoordinated

movements), diplopia (double vision), and nystagmus (repetitive and involuntary eye

movements)

 Sedation (to produce a state of calm or sleep)

Non-dose related

 Gingival hyperplasia (overgrowth of gum tissue around the teeth)

 Hirsutism (excessive hair growth in women due to excess of male hormones)

 Megaloblastic anemia (a condition when the bone marrow produces unusually large,

structurally abnormal, immature red blood cells)

 Hypersensitivity reactions (skin rashes and lesions, mouth ulcers)

 Hepatitis

 Fetal malformations

 Osteomalacia (due to abnormalities in vitamin D metabolism)

Carbamazepine CBZ (1974)

 Mechanism of action and indications are like that of phenytoin.

 Commonly used for mania.

Pharmacokinetics

 Available in oral form only.

 Well absorbed.

 80% protein bound.

Adverse effects

 Upset G.I.T

 Drowsiness, ataxia, headache, diplopia

  Hepatotoxicity (injury to the liver or impairment of the liver function)

 Congenital malformation (craniofacial anomalies & neural tube defects)

 Hyponatremia (sodium level in the blood is below normal) and water intoxication

 Hypersensitivity reaction (skin rashes, mouth ulcers)

 Blood dyscrasias (blood diseases)

Sodium Valproate or Valproic Acid (1990s)

Pharmacokinetics

 Available as capsule, syrup, I.V.

 Inhibits metabolism of several drugs such as Carbamazepine, Phenytoin, Topiramate

and Phenobarbital.

Mechanism of action

 Increase in GABA content of the brain.

Indications

 Effective against absence, myoclonic seizures, and convulsive seizures.

 Less effective than Carbamazepine for partial seizures.

 Used for mania.

Adverse effects

 Nausea, vomiting and GIT disturbances

 Increased appetite & weight gain

 Hair loss

 Hepatotoxicity

 Thrombocytopenia (a low blood platelet count)

  Neural tube defect (e.g., brain, spine, or spinal cord defect) in the baby

Second-Generation AEDs

Second-Generations AEDs as compared to First-Generation AEDs have:

 Good efficacy

 Fewer toxic effects

 Better tolerability

 Costly with limited clinical experience

Vigabatrin (1989)

Mechanism of action

 Inhibits GABA metabolizing enzyme.

 Increases GABA content in the brain (like valproate).

Adverse effects

 Visual field defects

 Psychosis and depression

Gabapentin (1993)

 May increase the activity of GABA or inhibit its re-uptake.

Adverse effects

 Somnolence (state of feeling drowsy, ready to fall asleep)

 Dizziness

 Ataxia

 Fatigue

Lamotrigine LTG (1994)

Pharmacological effects

 Resembles phenytoin in its pharmacological effects.

 Well absorbed from G.I.T

Mechanism of action

Inhibits excitatory amino acid release (glutamate and aspartate) by blockade of Na channels.

Adverse effects

 Skin rash

 Somnolence

 Blurred vision, diplopia

 Ataxia

 Headache

 Aggression

Topiramate (1996)

Pharmacological effects

 Well absorbed orally (80%).

 Food has no effect on absorption.

Mechanism of action

 Blocks sodium channels (membrane stabilization).

 Potentiates the inhibitory effect of GABA.

Indications
  One of the safest AED which can be used alone for partial, generalized convulsive,

and absence seizures.

Adverse effects

 Psychological or cognitive dysfunction

 Weight loss

 Sedation

 Dizziness

 Fatigue

 Urolithiasis (formation of stones in the kidney, bladder, urethra)

 Paresthesia (abnormal sensation)

Tiagabine (1997)

Indications

 Used for partial and generalized convulsive seizures.

Mechanism of action

 Inhibits GABA uptake and increases its level .

Adverse effects

 Asthenia (abnormal physical weakness or lack of energy)

 Sedation

 Dizziness

 Mild memory impairment

 Abdominal pain

Oxcarbazepine OXC (2000)

Mechanism of action

 Blockade of voltage-gated sodium channels.

Indications

 It is used either alone or with other medicines to treat partial seizures.

Adverse effects

 Fatigue

 Drowsiness

 Diplopia

 Dizziness

 Nausea and vomiting

 Rash

 Hyponatremia