Epilepsy Meds Flashcards

1
Q

What is the neuronal basis for epilepsy?

A

over-excitation

increased glutamate and aspartate

decreased inhibitory GABA

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2
Q

Generally, what do epilepsy drugs do?

A

suppress excitatory (glutamate)

enhance inhibitory (GABA)

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3
Q

The faster neurons fire in epilepsy, ___________

A

the faster meds can block the receptors to reduce activity

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4
Q

What drugs prolong fast inactivation of Na ion channels?

A

Stop/decrease APs by binding inside open gate:

Carbamazepine (azepines)
Lamotrigine
Phenytoin
Topiramate
Valproic acid
Lacosamide (amides)
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5
Q

What drug enhances slow inactivation of Na channels?

A

Lacosamide

–> doesn’t need activation gate of receptor open to work like other meds (can work with minimal open sodium channels)

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6
Q

What drugs block AMPA receptor on postsynaptic membrane so glutamate can’t activate it, thus decreasing APs/firing?

A

AMPA receptor antagonists:

topiramate
perampanel

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7
Q

What drug prolongs fast inactivation of Na channel (blocks it), blocks glutamate binding of AMPA receptor (antagonist), and increases frequency of GABA receptor transmission?

A

topiramate

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8
Q

What drug prevents binding of glutamate to NMDA receptor on postsynaptic membrane?

A

NMDA receptor antagonist:

Felbamate

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9
Q

T-type calcium channels are the hallmark of what seizure?

A

petit mal (absence)

inhibition of these channels decrease seizures

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10
Q

What drug inhibits T-type calcium channels and is only used for petit mal/absence seizures?

A

ethosuximide

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11
Q

What drug can block T-type calcium channel and sodium channels (prolong fast inactivation)?

A

Zonisamide

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12
Q

What drugs block synaptic vesicle SV2A (prevent glutamate from binding to presynaptic cleft, decreases release)?

A

levetiracetam

brivaracetam

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13
Q

What drugs block alpha 2 delta subunit of T-type calcium channels?

A

Gabapentin
Pregabalin

-both have GABA in name

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14
Q

What drug OPENS KCNQ potassium channels (pre and post) to hyperpolarize (stop AP) and stimulates GABA receptors in high doses?

A

Ezogabine

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15
Q

How does post-synaptic GABA transmission work?

A

when GABA receptor unoccupied–> inactive chloride channel

When GABA binds to its receptor–> chloride channel opens–> hyperpolarizes membrane to blunt AP

INHIBITORY

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16
Q

What is the significance of presynaptic GABA meds?

A

glutamate makes GABA, so meds increase conversion

meds that inhibit GABA metabolism (via GABA-T and SSD) or transport back to presynaptic neuron (via GAT-1) so there is more of it to inhibit neurons

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17
Q

What drug blocks GAT-1 (reuptake of GABA)?

18
Q

What drug blocks GABA-T (metabolizes GABA)?

A

Valproic acid

Vigabatrin

–>viGABATrin

19
Q

What drugs increase glutamic acid decarboxylase to produce more GABA?

A

valproic acid

gabapentin

pregabalin

20
Q

What drugs block the alpha-2-delta subunit of T-type calcium channels (decrease excitation) AND increase glutamic acid decarboxylase (produce more GABA)?

A

gabapentin

pregabalin

21
Q

What drug blocks SSD (stops metabolism of GABA)?

A

valproic acid

22
Q

What drugs enhance post-synaptic GABA transmission?

A

Barbiturates (phenobarbital/primidone)

Benzodiazapines (lorazepam, diazepam, clonazepam, clobazam)

Topiramate

23
Q

How do benzodiazepines work in seizures?

A

bind to distinct site–> potentiate GABA binding–> chloride channels open with greater frequency

need GABA present to work

24
Q

How to barbiturates work in seizures?

A

bind to distinct site on GABA and increase DURATION of chloride channel opening

don’t need GABA to work (high doses lethal c/t benzos)

25
What 2 drugs are broad spectrum in treating seizures with 3 MOAs?
topiramate valproic acid
26
What drug treats rare, severe forms of epilepsy?
cannabidiol only can be used in combo with other antiepileptic drugs
27
What are the broad warnings for all antiepileptic meds?
abrupt withdrawal or stopping of meds increases risk of status epilepticus suicidal ideation more likely
28
Phenytoin
zero order, saturable induces CYP450 gingival hyperplasia hypocalcemia--> bone issues
29
What drugs induce CYP450--> Vitamin D catabolism--> bone issues?
phenytoin carbamazepine phenobarbital valproic acid
30
Carbamazepine
auto-induction (loss of efficacy, recurrent seizures) inducer CYP450 leukopenia/neutropenia/thrombocytopenia --> bone marrow suppression
31
What is an analogue of carbamazepine that is less-potent CYP450 inducer (less bone marrow suppression) and doesn't have a toxic intermediate metabolite?
oxcarbazepine
32
Phenobarbital
fatality risk (high doses d/t not dependent on GABA for rxn) inducer CYP450 CNS depressant (how overdose with other depressants)
33
Vigabatrin
permanent vision loss can only prescribe with REMS program
34
Antiepileptic drugs and oral contraceptives
oral contraceptives metabolized by CYP450 since antiepileptics (some) are inducers, more is cleared --> increased risk for failure and unplanned pregnancy
35
Antiepileptic drugs and warfarin
increase clearance of warfarin (d/t induction of CYP450)--> less anticoag--> increase risk for clot
36
Antiepileptic drugs and HIV meds
increase clearance of HIV meds via induction of CYP450--> increased risk for HIV replication
37
What drugs inhibit conjugation of drugs by UGT--> accumulation of parent drug
valporic acid lamotrigine
38
What drugs induce conjugation of UGT--> reduce parent drug?
phenytoin carbamazepine phenobarbital especially when given with valproic acid
39
How do new drugs get around CYP450 system?
renal clearance renal insufficiency requires dose adjustments (elderly especially)
40
Treat status epilepticus
give benzodiazepine --> lorazepam IV classic fosphenytoin IV OR levetiracetam