• Abnormal brain activity that starts in one functional area and my spread ipsilateral
• Consciousness is preserved

• Results from abnormal temporal or frontal lobe activity and is associated with more complex motor symptoms
• Ictal phase = phase of active seizures
• Altered Consciousness

• Partial seizures may evolve to a generalized tonic-clonic seizure with sustained contraction (tonic) followed by rhytmic movements (clonic) of all limbs
• Loss of consciousness
• Preceded by auras

Primary Generalized

• Sudden, brief interruptions of consciousness
• Thought to involve T-type Ca2+ channels in thalamus
• Associated with a blank stare, occasional motor symptoms such as lip smacking, rapid blinking
• NOT preceded by auras

Primary Generalized

• Characterized by brief muscle contractions

Primary Generalized

• Abnormal brain activity begins generalized 
• Not preceded by symptoms of partial or complex seizure

1. Type, number, and distribution of voltage and ligand-gated ion channels
2. Biochemical modification of receptor: For example, phosphorylation of NMDA receptor increases Ca2+ conductance
3. Activation of cell signaling pathways: For example, activation of alpha receptor by NE results in increased K+ channel conductance
4. Changes in extracellular ion concentration
5. Remodeling of synaptic contacts: For example, an axon terminus closer to cell body increases probability of target neuron reaching threshold
6. Neurotransmitter metabolism by glial cells

• Initiating factor is thought to be hyperpolarization of relay neurons
• T-type Ca2+ channels located on these neurons are activated by hyperpolarization and cause short action potential bursts to the cortex
• As a result cortical neurons become activated via excitatory connections
• Excitatory input from the cortex activates the reticular thalamic neurons
• The activated GABAergic neurons hyperpolarize the thalamic relay neurons and reinitiate the cycle

MOA

• Slows recovery from Na+ channel inactivation at therapeutic concentrations
• Binds selectively to inactivated state of channel
• Na+ channel blockers inhibit PDS, the initiating factor in seizures

Uses

• Partial and tonic-clonic seizures
• Not for absence seizures

ADRs

• Nystagmus
• Diplopia
• Ataxia
• Gingival hyperplasia
• Hirsutism

MOA

• Slows recovery from Na+ channel inactivation at therapeutic concentrations
• Binds selectively to inactivated state of channel
• Na+ channel blockers inhibit PDS, the initiating factor in seizures

Uses

• Partial and tonic-clonic seizures
• Not for absence seizures

ADRs

• Diplopia
• Aplastic anemia
• Agranulocytosis
• Stevens-Johnson Syndrome
• Toxic epidermal necrolysis

MOA

• Slows recovery from Na+ channel inactivation at therapeutic concentrations
• Binds selectively to inactivated state of channel
• Na+ channel blockers inhibit PDS, the initiating factor in seizures

Uses

• Partial and tonic-clonic seizures
• Not for absence seizures

ADRs

• Improved toxicity profile compared to CBZ -- no hematological problems
• Stevens-Johnson Syndrome
• Toxic epidermal necrolysis
• Hyponatremia

MOA

• Use-dependent blockage of Na+ channels
• Inhibits high-voltage activated (HVA) Ca2+ channels
• Anti-folate NOT responsible for anti-seizure effect of drug

Uses

• Partial and tonic-clonic seizures
• Adjunctive therapy

ADRs

• Skin rashes -- SJS

MOA

• Prolongs Na+ channel inactivation
• Weak inhibition of T-type Ca2+ channels

Uses

• Adjunctive therapy for partial

ADRs

• Well tolerated
• Somnolence
• Ataxia
• Anorexia
• Nervousness
• Fatigue
• Weak carbonic anhydrase inhibition --> metabolic acidosis --> resp. rate increases
• Kindey stones

MOA

• Reduces low threshold Ca2+ currents (transient, T-type) in thalamic neurons

Uses

• First line for absence seizures
• Not effective for tonic-clonic

ADRs

• Principally GI effects
• Some CNS effects (drowsiness, lethargy, euphoria, dizziness, headache)

MOA

• Prolongs inactivation of voltage-gated Na+ channels

Uses

• Adjunctive therapies
• Partial and Lennox-Gastaut Syndrome

ADRs

• Cardiac conduction problems (PR and QT interval prolongation) likely arise from Na+ channel blockage on cardiac myocytes

MOA

• Prolongs inactivation of voltage-gated Na+ channels

Uses

• Adjunctive therapies
• Partial and Lennox-Gastaut Syndrome

ADRs

• Cardiac conduction problems (PR and QT interval prolongation) likely arise from Na+ channel blockage on cardiac myocytes

MOA

• GABA-A receptor agonist
• Increase frequency of Cl- channel opening
• Increased stimulus is required for neuron to reach threshold

Uses

• Intravenous for status epilepticus

ADRs

• Sedative and tolerance are major limitations
• Hyperactivity and aggression in children
• Cardiovascular and respiratory depression may occur after IV administration
• Sleep stages affected
• Dependence
• Nystagmus and diplopia

MOA

• GABA-A receptor agonist
• Increase frequency of Cl- channel opening
• Increased stimulus is required for neuron to reach threshold

Uses

• Intravenous for status epilepticus

ADRs

• Sedative and tolerance are major limitations
• Hyperactivity and aggression in children
• Cardiovascular and respiratory depression may occur after IV administration
• Sleep stages affected
• Dependence
• Nystagmus and diplopia

MOA

• GABA-A receptor agonist
• Increase frequency of Cl- channel opening
• Increased stimulus is required for neuron to reach threshold

Uses

• Atonic seizures
• Myoclonic seizures
• Absence seizures

ADRs

• Sedative and tolerance are major limitations
• Hyperactivity and aggression in children
• Cardiovascular and respiratory depression may occur after IV administration
• Sleep stages affected
• Dependence
• Nystagmus and diplopia

MOA

• GABA-A receptor agonist
• Increase frequency of Cl- channel opening
• Increased stimulus is required for neuron to reach threshold

Uses

• Adjunct for partial seizures

ADRs

• Sedative and tolerance are major limitations
• Hyperactivity and aggression in children
• Cardiovascular and respiratory depression may occur after IV administration
• Sleep stages affected
• Dependence
• Nystagmus and diplopia

MOA

• Inhibits GABA reuptake transporter (GAT-1)

Uses

• Adjunct for partial seizures with or without secondary generalization

ADRs

• Dizziness
• Somnolence
• Tremor

MOA

• Irreversible inhibitor of GABA tranaminase (GABA-T)

Uses

• Infantile spasms
• Approved for epilepsy in other countries

• Adjunct for partial seizures with or without secondary generalization

ADRs

• Dizziness
• Somnolence
• Tremor
• Permanent vision loss can occur -- peripheral vision

• AMPA/Kainate Receptors
• NMDA Receptors

These receptors are excitatory -- anti-seizure drugs are antagonists of these channels

MOA

• Prolongs Na+ channel recovery from inactivation
• Blocks T-type Ca2+ channels
• Enhances GABA-mediated transmission

Uses

• Absence seizures
• Generalized, partial, and myoclonic type seizures

ADRs

• Teratogenic
• GI effects
• Hepatotoxicity (rare)

MOA

• Designed as GABA mimetic but does not bind to GABA receptor
• Possibly increases synaptic GABA concentration and decreases HVA Ca2+ currents

Uses

• Adjunct for partial and tonic-clonic seizures

ADRs

• Somnolence
• Ataxia
• Nystagmus
• Dizziness

MOA

• Evidence for enhancing GABAergic transmission  and blocking HVA Ca2+ mechanisms
• Also binds to a synaptic vesicle-associated protein (this could alter NT release)

Uses

• Adjunct for partial seizures

ADRs

• Somnolence
• Asthenia
• Ataxia
• Dizziness

MOA

• Na+ channel inhibition
• Activates hyperpolarization K+ current
• HVA Ca2+ blocking emeriging in literature
• AMPA antagonist
• Enhances GABA transmission

Uses

• Adjunct for partial and primary generalized tonic-clonic seizures
• Shows promise for monotherapy

ADRs

• Metabolic acidosis due to carbonic anhydrase inhibition
• Paresthesia
• Somnolence
• Fatigue
• Weight loss

MOA

• Na+ channel inhibition
• Selective for the NR2B NMDA subtype
• HVA Ca2+ current decreases
• Inhibition and slight GABA enhancement

Uses

• Limited to intractable cases (Lennox-Gastaut)

ADRs

• Rare but severe aplastic anemia and acute liver failure

MOA

• Enhances GABA mediated transmission (allosteric and direct activation)

Uses

• Alternative for partial and tonic-clonic seizures (adult)
• Neonatal seizures

ADRs

• Sedation
• Tolerance
• Dependence
• Decreased cognitive function
• May worsen absence seizures
• Overdose danger
• Stevens-Johnson Syndrome
• TEN
• Hyperactivity in children

• The initiating factor in seizures
• Depolarizing event in neurons that precedes a partial seizure and potentially secondary generalized seizures
• Consists of slower wave calcium influx superimposed with action potential spikes