Pharmacology Of Seizures And Epilepsy

Front 1

What are the MOA's of the antiepilepsy drugs?

Back 1

Limit excitation - antagonize excitatory pathways
Enhance inhibition - Augment GABA inhibitory pathways

Front 2

What channels can be blocked in order to antagonize excitatory pathways?

Back 2

Voltage gated Na channels
Ligand gated Na channels
Ligand gated Ca channels
Low threshold (T type) Ca channels

Front 3

How can we augment GABA inhibitory pathways?

Back 3

Block GABA reuptake or metabolism
Potentiate GABAa receptor Cl- currents

Front 4

Why are there so many AEDs (anti-epilepsy drugs)?

Back 4

Approx 30% of treated patients still are not seizure free, and about 25% discontinue their meds due to significant side effects

Front 5

What drugs limit pre-synaptic excitation primarily by blocking voltage dependent Na channels?

Back 5

Old: Carbamazepine
Phenytoin
New: Lacosamide
Lamotrigine
Oxcarbazeine
Rufinamide
Zonisamide

Front 6

Of the drugs that block voltage gated sodium channels, which 3 are used to treat complex partial, partial, and general tonic clonic seizures?

Back 6

Old: carbamazepine, phenytoin
New: lamotrigine

Front 7

T or F: Carbamazepine and phenytoin are not used for treating absence seizures.

Back 7

True

Front 8

What are the complications with phenytoin?

Back 8

-Zero order pharmacokinetics - doubling dose does not double serum level, makes dosing difficult
-Inducer of CYP450 enzymes
-Distinct Toxicities: gingival hyperplasia, hirsutism, hypocalcemia, osteoporosis

Front 9

What are the complications with carbamazepine?

Back 9

Inducer of CYP450 enzymes
Distinct toxicities: leukopenia, neutropenia, thromocytopenia, hypocalcemia, osteoporosis

Front 10

Both phenytoin and carbamazepine induce CYP450; why does this matter?

Back 10

It influences the metabolism of other drugs the patient may be on, and there may be serious consequences

Front 11

T or F: Carbamazepine induces its own metabolism.

Back 11

True
By day 7, so much CYP has been induced you lose efficacy and get recurrence of seizures

Front 12

What is the problem with taking carbamazepine and oral contraceptives?

Back 12

Starting carbamazepine can increase clearance of oral contraceptives, leading to ~4-fold rise in OCP failure. Risk of unplanned pregnancy

Front 13

What is the problem with taking carbamazepine and warfarin?

Back 13

Starting carbamazepine can increase clearance of warfarin, leading to too rapid coagulation and an elevated risk for thrombosis

Front 14

T or F: AED's have a broad therapeutic window.

Back 14

False!
Very narrow therapeutic window that can be affected further by other drugs, foods, or beverages that can induce or inhibit CYP450

Front 15

T or F: Newer AED's have fewer problems attributable to drug interactions associated with hepatic metabolism, in general.

Back 15

True

Front 16

What two AED's can have black box warnings for Stevens-Johnson syndrome?

Back 16

Lamotrigine
Carbamazepine

Front 17

Which new AEDs exhibit mixed clearance and why is this important?

Back 17

Topiramate / oxcarbazepine
Levetiracetam / zonisamide
Minimizes drug interactions

Front 18

Which new AEDs exhibit 100% renal clearance?

Back 18

Gabapentin
Pregabalin

Front 19

What type of channels mediate a 3 Hz spike and wave activity in the thalamus, and what is this the hallmark of?

Back 19

T-type Calcium channels
Hallmark of absence (petit mal) seizures

Front 20

What drug is used ONLY for absence seizures and ONLY limits excitation (Ca channel)?

Back 20

Ethosuximide
Very narrow spectrum

Front 21

Which drugs enhance pre-synaptic GABAergic neuronal transmission?

Back 21

Tiagabine
Vigabatrin

Front 22

Tiagabine inhibits GABA ___________ and vigabatrin inhibits GABA __________.

Back 22

Re-uptake
Metabolism

Front 23

Which drugs enhance post-synaptic GABAergic neuronal transmission?

Back 23

Phenobarbital
Primidone
Benzodiazepines

Front 24

How do benzodiazepines work?

Back 24

Bind to distinct site causing an allosteric change
Potentiate GABA binding which opens chloride channels
*Phenobarbital behaves in a similar manner except at high doses it is GABA independent

Front 25

What are the complications with phenobarbital?

Back 25

Powerful, non-specific CNS depression
Cause significant sedation
Lethal respiratory depression
Abuse and addiction potential

Front 26

What drugs are used to treat status epilepticus initially? What if they don't stop the seizure?

Back 26

Lorazepam / diazepam i.v.
If seizure didn't stop, fosphenytoin i.v. (sodium channel antagonist)

Front 27

What is the goal of treating status epilepticus?

Back 27

Stop seizure/EEG bursts

Front 28

What two drugs have multiple MOA's and are considered broad spectrum AEDs?

Back 28

Valproic acid
Topirimate

Front 29

What are the MOAs of valproic acid and topirimate?

Back 29

Valproic acid: Blocks voltage gated Na channels, blocks T-type Ca channels, Increases GABA

Topirimate: Blocks voltage gated and ligand gated Na channels, increases GABA, and potentiates GABAa receptors

Front 30

What are the distinctive toxicities of valproate?

Back 30

Weight gain
Hepatotoxicity

Front 31

Which AEDs are Class D teratogens?

Back 31

Valproic acid**
Carbamazepine
Phenytoin

Front 32

T or F: Valproate and lamotrigine inhibit conjugation of drugs by UGT enzymes, leading to accumulation of parent drug.

Back 32

True

Front 33

What is the MOA of gabapentin?

Back 33

Binds to voltage dependent Ca channels

Front 34

What is the MOA of leviteracetam?

Back 34

Binds to synaptic vesicle protein SV2A - blunts glutamate release
Well tolerated; no CYP interaction

Front 35

What is the MOA of pregabalin?

Back 35

Multiple MOAs
100% renal clearance

Front 36

What is the MOA of ezogabine?

Back 36

Opens voltage gated K channels

Front 37

What is one major cause of non-compliance with AEDs?

Back 37

Common side effects which include: drowsiness, fatigue, clumsiness, dizziness, nystagmus, insomnia, confusion, headache, etc