Epilepsy is a brain disorder that causes recurrent seizures and affects over 65 million people worldwide. Seizures occur when there is excessive or synchronous neuronal activity in the brain. The presentation of seizures can vary and include loss of consciousness, involuntary movements, or muscle spasms. Epilepsy has various causes like brain malformations, low oxygen levels during birth, head trauma, genetic factors, or Alzheimer's disease. Current treatments for epilepsy include first and second generation antiepileptic drugs that work by blocking sodium channels, enhancing GABA activity, or blocking calcium channels to reduce neuronal excitability. Newer antiepileptic drugs target glutamate receptors or proteins like SV2A to control seizures.
3. Epilepsy
Introduction -
Seizure” is a paroxysmal alteration of neurologic function caused by
the excessive, hypersynchronous discharge of neurons in the brain.
seizures can leads to loss of consciousness, disturbance of
movement, muscle spasms, autonomic and mental functions
During the seizure, neurons may fire 500 times faster than normal
neurons
The ‘Epilepsy’ is a group of neurological disorders all of which
exhibit periodic recurrent seizures.
Epilepsy is a brain disorder that affects at least 12 millions people in
India and 65 millions of people worldwide.
5. IN NEWBORNS–
• Brain malformation
• Lack of oxygen during or before delivery or at birth
• Low level of blood sugar, blood calcium, magnesium or other electrolyte
disturbance
• In born errors of metabolism
• Intracranial haemorrhage
• Maternal drugs used
CHILDRENSAND ADULTS
• Head trauma
• Genetic factors
ELDERLY
• Stroke
• Alzheimer disease
• Head trauma
CAUSES
6. Pathophysiology
Paroxysmal discharges in cortical neurons
A seizure originates from grey matter of any cortical or subcortical area
Abnormal firing of neurons
Breakdown of normal membrane conductance & inhibitory synaptic currents
Locally widely
Focal seizure Generalized seizure
7. Abnormality of Potassium conductance
Defect in voltage sensitive ion channels
Deficiency in membrane ATPase
Neurone membrane instability
Seizures
Deficiency of inhibitory neurotransmitters
Increase in excitatory neurotransmitters
promotes
Abnormal neuronal activity
Seizure
8.
9. Treatment
1. First-generation AEDs:
- Examples: Phenobarbital, Phenytoin, Carbamazepine, Valproic Acid
- These are older AEDs developed earlier and have been in use for a long time.
2. Second-generation AEDs
- Examples: Lamotrigine, Levetiracetam, Topiramate, Oxcarbazepine
- These are newer AEDs that have been developed in recent years and offer alternative treatment options.
3. Sodium Channel Blockers:
- Examples: Phenytoin, Carbamazepine, Lamotrigine
- inhibits voltage-gated sodium channels, reducing the excitability of neurons.
4. GABAergic Drugs:
- Examples: Phenobarbital, Benzodiazepines (e.g., Diazepam, Clonazepam)
- Enhance the activity of gamma-aminobutyric acid (GABA)
5. Calcium Channel Blockers:
- Examples: Ethosuximide, Valproic Acid
- Block calcium channels, reducing the influx of calcium ions into neurons stabilizing neuronal excitability.
6. Glutamate/Glutamate Antagonists:
- Examples: Topiramate, Felbamate
- These AEDs modulate the activity of glutamate
10. New agents
1. Brivaracetam (Briviact):
• It is used as an add-on treatment for partial-onset seizures in adults and adolescents aged 16 years
and older.
• Mechanism of Action (MoA): Brivaracetam is an antiepileptic drug that works by selectively binding to
synaptic vesicle protein 2A (SV2A) in the brain. Its exact mechanism of action is not fully understood.
2. Perampanel (Fycompa):
• It is approved for the treatment of partial-onset seizures with or without secondary generalized seizures
in patients aged 12 years and older.
•Mechanism of Action (MoA): Perampanel is a selective antagonist of the AMPA glutamate receptor. It
works by inhibiting excessive glutamate activity, which is believed to contribute to seizures.
3. Stiripentol (Diacomit):
• It is used as an adjunctive treatment for Dravet syndrome in patients aged 2 years and older, in
combination with other antiepileptic drugs.
•Mechanism of Action (MoA): Stiripentol's exact mechanism of action is not fully understood. It is believed
to potentiate the inhibitory effects of gamma-aminobutyric acid (GABA), a neurotransmitter that helps
11. Carl E. Stafstrom1 and Lionel Carmant2 1 Division of Pediatric
Neurology, Departments of Neurology and Pediatrics, Johns
Hopkins University School of Medicine, Baltimore, Maryland;
Seizures and Epilepsy: An Overview for Neuroscientist
RANG AND DALE’S Pharmacology; page no. 540 to 550
Abdul Waheed*, Swati Pathak, Roohi Mirza Department of
Pharmacology, Amity Institute of Pharmacy, Amity University,
Noida, U.P. India ; Epilepsy: A brief review
References