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what are some facts about seizures and epilepsy?

10% of population will have one seizure in their life
1% of population has epilepsy (2 unprovoked seizures)
Epilepsy has a bimodal distribution: more common in early childhood and in elderly
Epilepsy is not a single entity and rather a sign of several seizure types with various etiologies
70-80% of seizures can be controlled with one AED.
10-15% will require more than one medication and 10-15 % are medically refractory.


what is a seizure?

Seizure is a sudden, excessive, and synchronous discharge of cerebral neurons.
Depending on the part of brain involved, the abnormal electrical activity may result in:
Transient loss of consciousness
Abnormal movements
Atypical or odd behavior
Distorted perception

Status epilepticus: If the seizure continues more than 5 minutes, or several seizures with no gain of consciousness over 5 minutes.


what are two types of seizures?

Focal onset
(partial seizure)
- one part of the brain

- many parts or pathways goign crazy


for generalized onset seizure, what is absence seizure?

Activation of reticular neurons (NRT) inhibits thalamocortical relay neurons (TR) which generate Ca2+-mediated action potentials that excite the Pyramidal Cortical neurons in burst firing → Absence seizure


what is a partial (onset) seizure?

- Partial (onset)
Simple Partial (e.g. partial sensory seizure: aura)
Complex Partial (e.g. temporal lobe seizure)
Secondarily generalized

All AEDs are effective
(exception: ethosuximide)


what's a generalized seizure?

Generalized (onset): no aura
Generalized tonic clonic (GTC)

AED options are more limited


what is epileptiform discharge:: paroxysmal depolarization shift?

A prolonged depolarization on top of which several action potentials may occur

Several receptor channels are involved at each stage

The diagram helps predict how AEDs may work.


what is the mechanism of action?

Voltage Gated Sodium Channels
- Blockade of fast inactivated channels
- Facilitation of slow inactivation phase
Potentiation of GABAergic mechanisms
Blockade of Calcium channels
Blockade of Glutamate receptor channels (NMDA, AMPA)
Opening of voltage gate potassium channels


for mechanism of action what do voltge gated sodium channel blockades have to do with it?

1- Voltage gated Na+ channel blockade:
Prolongation of the “fast” inactivated state of channel → ↑ refractory period of the neuron
Zonisamide (not the main mechanism)
Phenobarbital and Valproic acid at higher doses

Potentiation of the slow-inactivated channels


what does pehnytoin do?

Pharmacokinetic: Zero order Kinetic
(metabolism saturation)
Metabolism P450: Beware of toxicity
Enzyme inducer
Specific side effects:
Gum hypertrophy
Cerebellar atrophy: imbalance
Teratogenic: fetal Hydantoin syndrome


for carbamazepine and oxcarbazepine what do these have to do with anyting?

P450 metabolism
Enzyme inducer ( for Oxcarb)
induces its own metabolism
Dose adjustment is required
May lower other medications level (e.g. oral contraceptives)

Side effects/ interaction
Rash (same for Oxcarb)
Hyponatremia (increase for Oxcarb)
Hepatotoxicity (decrease for Oxcarb)
Bone marrow suppression (decrease for Oxcarb)
Osteoporosis (decrease for Oxcarb)


what about lamotrigine?

Valproic Acid (VPA) → ↓ metabolism (glucuronidation) → 2 fold ↑ in half life
If combined with VPA, slowly increase the dose to avoid toxicity/ side effects
Levels ↓ significantly in pregnancy or with oral contraceptive as the glucuronidation is induced by ↑ estrogen → ↑ the dose as needed

Side effects
Severe skin rash → to avoid, titrate up the dose slowly every 2 weeks for the first few weeks
Believed to be safe in pregnancy, a few cases of cleft lip are reported.
Try not to combine with other AEDs in pregnancy
Always add folate


what about lacosamide?

Prolongation of cardiac conduction (PR interval) → may lead to heart block
Do baseline ECG in patients with known cardiac disease or conduction defects.


what is valproic acid (VPA)?

Heavy protein binding → displaces other protein bound medications → toxicity (e.g. with phenytoin)
Blocks liver metabolism → ↑ Lamotrigine, Phenobarbital levels
VPA level is decreased by P450 inducers (e.g. phenytoin)
Side effects:
Platelet dysfunction (avoid in brain hemorrhages)
Hair loss
Weight gain
Polycystic ovaries → infertility in young women
High teratogenicity
(never use in young women if other choices are available)