Seizures Flashcards
1
Q
pathophysiology of seizures
A
- Population of pathologically excitable neurons
- Increase in excitatory GLUtaminergic activity through recurrent connections in order to spread the discharge
- Reduction in the activity of the normally inhibitory GABAnergic projections.
2
Q
Carbamazepine
A
- use for partial (focal) and secondarily generalized tonic-clonic seizures
- slows rate of recovery of voltage-activated Na+ channels from inactivation –> less firing
- Carbamazepine induces CYP2C, CYP3A, and UGT, enhancing the metabolism of drugs degraded by these enzymes, including oral contraceptives (3A4)
- may induce Stevens-Johnson Syndrome in patients with the human leukocyte antigen (HLA)-B*1502 allele; almost exclusively in Asians.
3
Q
Explain why the clearance of phenytoin changes with dose…
A
- one of the few drugs for which the rate of elimination varies as a function of its concentration (i.e., the rate is nonlinear).
- Zero order kinetics
- The plasma t1/2 of phenytoin ranges between 6 and 24 hours at plasma concentrations below 10 μg/mL but increases with higher concentrations; as a result, plasma drug concentration increases disproportionately as dosage is increased
4
Q
Describe the rationale for monitoring plasma concentrations of many antiepileptic drugs
A
5
Q
Ethosuximide
A
- Primary tx for Absence (generalized, non-convulsive) seizures
- MOA reduces low threshold Ca2+ currents (T-type currents) in thalamic neurons
- partially metabolized by CYP3A4; inducers of CYP3A4 may decrease serum concentrations
- Adverse effects: behavorial changes, Psychotic behavior, systemic lupus erythematosus (SLE)
6
Q
Valproic Acid
A
- Works for most seizures! Drug of choice for primarily generalized tonic-clonic seizures; works for complex partial seizures, absence seizures, myoclonic and atonic seizures, photosensitive epilepsy and juvenile myoclonic epilepsy.
- MOA: “all of the above”, inhibits repetitive firing, prolonged recovery of voltage-activated Na+ channels from inactivation,
7
Q
Phenytoin
A
- partial and secondarily generalized tonic-clonic seizures, but is no longer considered a drug of first choice because of its complicated pharmacokinetics, adverse effect profile and frequent drug-drug interactions.
- MOA limits the repetitive firing of action potentials by slowing of the rate of recovery of voltage-activated Na+ channels from inactivation
- a strong enzyme inducer (like carbamazepine); that can reduce serum concentrations and possibly the effectiveness of many other drugs
Asian patients who test positive for HLA-B*1502 may have an increased risk of serious skin
8
Q
Levetiracetam
A
- primary therapy for focal seizures, primary or secondary generalized tonic-clonic seizures and myoclonic sizures
- MOA inhibits neuronal burst firing; mechanism unknown; may relate to a synaptic vesicle protein, SV2A.
- Drug interactions: None
9
Q
Topirimate
A
- focal and primarily generalized tonic clonic seizures
- MOA reduces voltage-gated Na+ currents in cerebellar granule cells and may act on the inactivated state of the channel similar to phenytoin, activates a hyperpolarizing K+ current, enhances postsynaptic GABAA-receptor currents.
- mild inducer of CYP3A and an inhibitor of CYP2C19
10
Q
Carbamazepine and phenytoin decrease the concentration of what other drug?
A
topiramate
11
Q
Tiagabine
A
- partial (focal) seizures (used as an adjunct, not primary monotherapy)
- MOA inhibits the GABA transporter, GAT-1, and thereby reduces GABA uptake into neurons and glia.
- no cyp interactions
- May cause suicidal thoughts
12
Q
Seizure definition
A
Abnormal synchronized electrical activity in the brain
13
Q
Seizure Classification
A
- Generalized - Both hemispheres, synchronized
- Convulsive = grand mal or tonic clonic
- Non-convulsive = petit mal or absence
- Focal - Local onset
- Simple = no alteration of consciousness
- Motor, sensory, autonomic, psychic
- Complex = impaired or loss of consciousness
- Simple = no alteration of consciousness
- Special Epileptic Syndromes
- Febrile seizures, others…
