Antiseizure Medications Flashcards
Seizure
: Excessive neuronal discharge characterized as brief, involuntary, episodic
Convulsion
Violent involuntary contraction of voluntary muscles
Epilepsy
Chronic seizure disorder
SZ Epi
8% of population have at least 1 seizure in lifetime
About 0.5-1% have epilepsy (chronic seizures)
80% controlled with standard therapy
500,000 with uncontrolled epilepsy
Model for Unstable - Excessive Neurotransmission Seizures
(1) Excessive activity in neuron A
(2) Widespread input from its dendrites triggers too much axonal flow, mediated by voltage-sensitive sodium channels (VSSC) (valproate target)
(3) This in turn overly activates voltage-sensitive calcium channels (VSCC) linked to glu (lamotrigine target)
(4) Triggering of excessive, chaotic, unpredictable neurotransmission from neuron A to neuron B
(5) Seizure activity is then by detected by postsynaptic NMDA receptors on neuron B
(6) Subsequent excitation of its own VSSC and so on
Widespread input from its dendrites triggers too much axonal flow, mediated by voltage-sensitive sodium channels (VSSC) (__________ target)
valproate
This in turn overly activates voltage-sensitive calcium channels (VSCC) linked to glu (___________ target)
lamotrigine
Generalized Seizures
Generalized Tonic-Clonic (Grand mal) [30%]
Mechanism
Initiation occurs locally –> loss of GABA inhibitory tone
Propagation due to ↓ GABA tone over large area plus ↑ response to glutamate and Na+-channel excitation
Generalized Absence (Petit mal) [10%] Mechanism
Oscillatory stimulation of thalamic-cortical circuitry - activation of low-threshold T-type Ca++ channels
ethosuxmide
Valproic acid in prego
NO
Simple Partial [10%]
Key feature is preservation of consciousness
Usually of cortical origin in restricted region (e.g., Jacksonian motor seizures reflect topographic organization of cortex)
Complex Partial [35%]
Loss of or impaired consciousness
Psychomotor: Involves limbic as well as temporal / frontal cortex (emotional)
Secondary Generalization
Loss of consciousness, include other areas/muscle groups
Mechanism: Involves initiation (rather than propagation) - difficult to treat
Most difficult to treat?
Generalized
intioition
Mechanisms of Antiseizure Drugs Treatment
Elevating seizure threshold –> stabilize membrane
Limiting propagation –> reduce synaptic transmission or nerve conduction
Drugs are more effective in limiting propagation (generalized seizures) than in preventing initiation (partial seizures)
Status Epilepticus
State of recurrent major motor seizures between which patient does not regain consciousness
Mortality of 20-25% - death can occur from respiratory arrest or circulatory collapse
Status Epilepticus
Treatment Options:
Initial therapy IV diazepam (lorazepam or midazolam) until seizures stop or 20 mg given
Then start phenytoin or fosphenytoin slow infusion
If seizures persist IV phenobarbital until seizures stop
If seizures still continue, pentobarbital or propofol infusion with pressor support
Prego
NOTE: Risk to offspring from antiepileptic drugs generally less than risk from maternal seizures during pregnancy
Risk of birth defects 2-3-fold higher if mother on AEDs
• Cleft palates, skeletal abnormalities, CNS-cardiac problems
• Most (> 90%) deliver normal babies
Difficult to separate medication effect from disease effect, but probably medication
• Valproate and phenobarbital may have highest risk
• Carbamazepine, phenytoin, lamotrigine - lower rates
• Newer agents with low rates include levetiracetam, gabapentin, oxcarbazepine
Monotherapy preferred
• Decreases fetal exposure minimizes teratogenicity
• Incidence highest with multidrug therapy
Drug levels generally lower during pregnancy
• Enhanced metabolic clearance
• Altered protein binding
• Adjust dosage accordingly, especially for lamotrigine
Vitamin K deficiency and hemorrhage in newborn
• Phenytoin, carbamazepine, and phenobarbital
• Recommend vitamin K supplementation to mother in final month of pregnancy and for the newborn
