Antiseizure (General) Flashcards
Epileptic Seizure
Abnormal excessive and synchronous neuronal activity in the brain
Epilepsy
- At least two unprovoked seizures that occur less than 24 hours apart
- One unprovoked seizure and a probability of further seizures of at least 60% occuring in the following 10 years
- Diagnosis of an epilepsy syndrome
Focal Seizures
Seizures that are focused on one part of the brain
Simple Partial Seizure
No impairment of consciousness
Motor symptoms (Muscle Twitching)
Duration < 60 seconds
Complex Partial Seizure
Altered consciousness
- Not aware of surroundings
- Not unconscious
Motor automatism (Chewing or Lip Smacking)
Duration 1-2 minutes with postictal confusion after
Secondary Generalized
A focal seizure that becomes generalized
Generalized Seizures
Widespread involvement of brain
Can be convulsive/non-convulsive
Generalized Tonic-Clonic (Grand Mal)
Loss of consciousness (Stereotypical Seizures)
Hyperextension of body, rhythmic full body contractions (Tonic and Clonic Phases)
Duration 1-2 minutes with Postictal Confusion, stupor, and headache
Absence (Petit Mal)
Sudden Impairment of Consciousness
- No convulsions
Duration 5-10 seconds
Starts in childhood
Myoclonic
Sudden muscle contractions, no loss of consciousness
Duration of jerks lasts milliseconds
Pathophysiology of Seizures
Imbalance of Excitatory/Inhibitory
- When neuronal activity gets synchronized in the brain
Pathophysiology of Seizures (Excitatory Mechanisms)
Too Much Excitatory Mechanisms
- Glutamate Receptors (NMDA, AMPA)
- Sodium and Calcium Influx
Pathophysiology of Seizures (Inhibitory Mechanisms)
Not enough Inhibitory Mechanisms
- GABA
- Voltage Gated Potassium Channels
- Calcium Dependent Potassium Channels
Antiseizure Drug Limitations
Suppresses seizures by inhibiting abnormal neuronal discharge (Symptomatic)
Not Curative
Antiseizure Drugs Mechanism of Action
Enhancement of GABA actions
Sodium / Calcium Channel Blockers
Inhibition of Glutamate Receptors
Potassium Channel Openers
GABA Modulators (Enhance GABA Receptor Activation)
Phenobarbital
Benzodiazepines
GABA Modulators (Inhibit GABA Reuptake)
Tigabine (GAT 1 Inhibitor)
GABA Modulators (Inhibit GABA Breakdown)
Vigabatrin (Irreversible Inhibitor of GABA transaminase)
GABA Modulators (Increased GABA Activity)
Gabapentin
Pregabalin
Sodium Channel Blockers
Phenytoin
Carbamazepine
Lacosamide
Lamotrigine
Zonisamide
Sodium Channel Blockers (Targets)
Prolongs refractory period of Na+ Channels
–> Will only affect channels that have already fired and are inactive
–> Channel will not refire in refractory period
T-Type Channel Activity responsible for what kind of seizures
Absence Seizure
(Hyperactivation of T-Type Ca2+ Channels causes absence seizures)
T-Type Channel (ASM)
Ethosuximide
Valproic Acid
Both work only with absence seizures
P/Q-Type Calcium Channel Mechanism
Modulates the release of neurotransmitters like GABA
Increases activity of GABA
P/Q-Type Calcium Channel (ASM)
Gabapentin
Pregabalin
Levetiracetam and Brivaracetam
- What kind of seizures
- Found where
- Mechanism
Works on all type of seizure (Broad-Spectrum)
Found in presynaptic neuron
Modulates neurotransmitter vesicular release of presynaptic neuron
- Bind to synaptic vesicle protein 2A (SV2A) which controls release of various neurotransmitters
–> Increased release of GABA
–> Decreased release of glutamate
Perampanel
- Mechanism
Non-Competitive AMPA Receptor Antagonist
–> Prevents action of excitatory receptor
ASM with Multiple Mechanisms
Valproic Acid
Topiramate
Felbamate (Lots of side effects)
What is the rule with combining ASM
Do not combine drugs with the same mechanism (Phenobarbital with Barbiturate)
Can combine broad spectrum drugs, these are synergistic
What drugs treat Focal Seizures
All anti-seizure drugs will work
Na+ Blockers:
- Carbamazepine, Lamotrigine, Phenytoin
Broad Spectrum:
- Levetiracetam (SV2A Modulator)
Exception: Ethosuximide (T-Type Ca2+)
What drugs treat Generalized Tonic-Clonic Seizures
Na+ Blockers:
- Carbamazepine, Lamotrigine, Phenytoin
Broad Spectrum:
- Levetiracetam (SV2A Modulator)
- Valproic Acid
What drugs treat Absence Seizures
T-Type Ca2+ Channel Blockers
- Ethosuximide
- Valproic Acid
What drugs treat Myoclonic Seizures
Broad Spectrum:
- Valproic Acid
What ASM should not be used to treat absence/myoclonic seizures
Na+ Blockers are ineffective and may worsen absence/myoclonic seizures
Other uses of antiseizure drugs
Bipolar Disorder
Anxiety
Neuropathic Pain
Migraine Prophylaxis
