What are seizures?
Symptoms?
Seizures are sudden, excessive, and synchronous discharges of neurons
10% of pop will have 1 seizure in life
Epilepsy has a bimodal distribution: more common in early childhood and in elderly
GABA receptor major in these ones
Can create a recurring circuit if you get one seizure
The abnormal electrical activity may result in:
Transient loss of consciousness, abnormal movements (overstim of area of brain involved with movements), atypical or odd behaviour, distorted perception
Slide 5
What is the first (1 of 2) type of seizures: partial/focal (onset)?
Happening in a distinct area of brain
- simple partial, partial sensory seizure
- aura (can sense something)
- complex partial, temporal lobe seizure
- secondarily generalized
All AEDs are effective except ethosuximide
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What is the second (2 of 2) type of seizures: generalized (onset)?
No aura (can’t sense somethings up) Incorporate much of brain if not all of it - generalized tonic clonic (GTC) - tonic/atonic - absence (go blank) - myoclonic
AED options are more limited (want to be more selective, if you suppress some areas too much you can kill the patient)
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What are the 11 drugs used for partial seizures (simple, complex, secondarily generalized)(has
Carbamazepine Lacosamide Oxcarbazepine Phenytoin Phenobarbital Primidone Tiagabine Vigabatrin Gabapentin Pregabalin Ezogabine
What are the 6 drugs used for generalized and partial onset seizures?
Felbamate Lamotrigine Levetiracetam Topiramate Valproate Zonisamide
What is the one drug used for absence seizures?
Ethosuzimide
What are the 6 mechanisms of actions of all the antiepileptics?
- Voltage gated sodium channels- blockade of fast inactivated channels (slow inactivation phase)
- Potentiation of GABAergic mechanisms- reduce likelihood you reach AP
- Blockade of calcium channels- block Ca channels, block neurotransmitter release, lower seizure activity
- Blockade of glutamate receptor channels (NMDA, AMPA)- NMDA are ones that can drive cell death, AMPA does not (they recruit NMDA)
- Opening of voltage gated potassium channels- potassium rushes out and quickly repolarizes membrane potential
- Antagonism of exocytosis
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Which drugs use the first (1) mechanism: voltage gated sodium channels?
Partial seizures: Carbamazepine (1) Lacosamide (1) Oxcarbazepine (1) Phenytoin (1) Phenobarbital (1, 2)
Generalized and partial onset seizures:
Lamotrigine (1)
Valproate (1, 2, 3, 5)
Zonisamide (1, 3)
Absence seizures:
None
Which drugs use the second (2) mechanism: potentiation of GABAergic mechanisms?
Partial seizures: Phenobarbital (1, 2) - barbiturate Primidone (2) - barbiturate Tiagabine (2) Vigabatrin (2)
Generalized and partial onset seizures:
Felbamate (2, 4)
Topiramate (2, 4)
Valproate (1, 2, 3, 5)
Absence seizures:
None
Which drugs use the third (3) mechanism: blockade of calcium channels?
Partial seizures:
Gabapentin (3)
Pregabalin (3)
Generalized and partial onset seizures:
Valproate (1, 2, 3, 5)
Zonisamide (1, 3)
Absence seizures:
Ethosuzimide (3)
Which drugs use the fourth (4) mechanism: blockade of glutamate receptor channels (NMDA, AMPA)?
Partial seizures:
None
Generalized and partial onset seizures:
Felbamate (2, 4)
Topiramate (2, 4)
Absence seizures:
None
Which drugs use the fifth (5) mechanism: opening of voltage gated potassium channels?
Partial seizures:
Ezogabine (5)
Generalized and partial onset seizures:
Valproate (1, 2, 3, 5)
Absence seizures:
None
Which drugs use the sixth (6) mechanism: antagonism of exocytosis?
Partial seizures:
None
Generalized and partial onset seizures:
Levetiracetam (6)
Absence seizures:
None
What are the 4 antiepileptics not metabolized by hepatic enzymes?
Gabapentin
Pregabalin
Vigabatrin
Levetiracetam
These are excreted by kidney
How are drug interactions possible with these drugs?
By blocking antiseizure drug metabolism
By displacing the drugs from plasma proteins binding sites (increase potency)
Induction of antiseizure drug metabolism (by rifamipin or other antiseizure meds) (decreases potency)
What are the 3 liver P450 enzyme inducers?
Phenytoin
Phenobarbital
Carbamazepine
Slide 25
What is the ideal treatment of epilepsy?
Effective (in all seizure types) No adverse effects No long term risks No interactions with other drugs Long lasting action Safe in pregnancy Inexpensive Start 1 AED, low, go slow Taper slowly If adding 2nd AED, add one with second mechanism of action Always add folate in pregnancy
