Epilepsy Flashcards
Identify the site where the following drugs act
Either gluatminergic/GABAergic synapes, presynaptic /postsynaptic
1. Phenytoin, CBZ, LTG, Lacosamide
2. Ethusiximide, LTG, Gabapentin, Pregabalin
3. Levetiracetam
4. Lacosamide
5. Felbamate
6. Topiramate, Perampanel
ALL are glutaminergic
- PreS VG Na channel
- PreS VG Ca++ channel
- PreSSV2A synaptic vesicle proteins
- PreS Collapsin response mediator protein 2 (CRMP2)
- PostS NMDA
- PostS AMPA
Identify the site where the following drugs act
Either glutamatergic/GABAergic synapes, presynaptic /postsynaptic
1. Tiagabine
2. Vigabatrin
3. Benzos and Barbiturates
ALL act in the GABAergic synapse
- PreS GABA transporter
- PreS GABA transaminase
- PostS GABA A receptor
What is AKA diphenylhydantoin?
Phenytoin
How does phenytoin affect Na channels?
Binds to and Prolongs the inactivated state of the Na channel resulting in decreased glutamate release– PreSynaptic Glutaminergic
What are the advantages of fosphenytoin over phenytoin?
Can be given IM
How does uremia affect phenytoin?
Low protein levels causes more unbound fraction of the drug.
Besides gingival hyperplasia and hirsutism what other adverse effects do we expect from phenytoin? Think cerebellar and eye movements
Ataxia, nystagmus, diplopia
But also remember osteomalacia from abnormal vitamin D metabolism
What are the most common dose related adverse effects of CBZ?
Diplopia and ataxia
Hyponatremia, aplastic anemia, leukopenia, agranulocytosis and unsteadiness also occurs
What is the advantage of eslicarbazepine over CBZ and OxCBZ?
Once a day dosing
What derivative of barbituric acid is a treatment option for essential tremor and is converted to Pb?
Primidone
Besides binding to the GABA receptor what is the other important MOA of Pb?
Similar to phenytoin on Na channels presynaptic glutaminergic
What is the therapeutic level of
- Phenobarbital
- Carbamazepine
- Phenytoin
- Valproic acid
- 10-40mcg per ml
- 4-8 mcg
- 10-20 mcg per ml
- 50-100mcg per ml
What are the deadly side effects of felbamate?
heptitis and aplastic anemia
How does the binding of pregabalin and gabapentin to Ca++ channels prevent seizures?
Decrease in Ca++ entry in the presynaptic terminal results in decrease in the release of glutamate in the synaptic cleft.
How are pregabalin and gabapentin metabolized?
Trick question. They ARE NOT metabolized– rather excreted unchanged in the urine
What are the 2 MOA of Lacosamide?
- Binds the SLOW inactivation of the voltage gated Na channels– PREFERENTIALLY AFFECTS DEPOLARIZED NEURONS
- Binds to collapsin response mediator protein CRMP-2
Besides the blockade of Na channels how else does lamotrigine function?
Inhibits Ca++ channels N and P/Q types
How does valproate affect lamotrigine levels?
Causes a TWOFOLD INCREASE in the drug’s half life
What drug was designed to inhibit GAT-1 thereby increasing GABA available?
Tiagabine
What are the MOA of Topiramate?
- Na blocking
- L-type Ca channels
- GABA postentiation on receptor
- Decreases the excitatory effect of kainate on glutamare receptors
What drug inhibits GABA-T the enzyme responsible for the degradation of GABA?
Vigabatrin
What AED causes peripheral visual field defects in 30-50% of patients?
Vigabatrin
What type of Calcium channels does ethusuximide affect?
T-type Ca channels that are thought to provide a pacemaker current in the thalamic neurons responsible for generating rhythmic cortical discharge
Enumerate all the MOA of Valproic acid
- Blocakde of NMDA receptors
- Facilitate Glutamic Acid Decarboxylase for GABA synthesis
- Inhibit GAT 1 to increase GABA as well
- Na channel blocker
How does VA affect liver enzymes?
Inhibit– increasing lamotrigine, phenytoin, pb, CBZ
What are the idiosyncratic reactions observed with Valproic acid?
- Heptotoxicity needing L-carinitine supplementation
2. Thrombocytopenia
What are the two drugs for treatment of infantile spasms?
Corticotropin and Vigabatrin
What is the MOA of zonisamide?
Also by Na block and T type Calcium block
What is the only AED drug that works by facilitating the potassium channel in the presynaptic nerve terminal?
Retigabine
Stiripentol that acts by enhancing GABA transmission by prolonging the opening of Cl- channels in the brain is used for what epilepsy syndrome?
Severe myoclonic epilepsy of infancy or DRAVET syndrome
How would topiramate affect birth control pills?
less effective birth control
What is the common moa of zonisamide and ethusuximide? Go beyond the affected ion.
Reducing low threshold t type calcium currents affecting thalamic rhythmic cortical dc respnsible for absence (specific for ethusuximide)
