Pharm: Epilepsy - Segars

Question 1

carbamazepine

Answer 1

Na-channel blocker

Question 2

oxcarbazepine

Answer 2

Na-channel blocker

Question 3

lacosamide

Answer 3

Na-channel blocker

Question 4

lamotigrine

Answer 4

Na-channel blocker

Question 5

felbamate

Answer 5

NMDA-r blocker

Question 6

tiagabine

Answer 6

GAT-1 channel blocker (PREsynaptic, GABA promoter)

Question 7

vigabatrin

Answer 7

GABA-T enzyme inhibitor (PREsynaptic, GABA promoter)

NOTE: GABA-T converts GABA -> succinic semi-aldehyde)

Question 8

phenobarbital

Answer 8

POST synaptic GABA promoter

Question 9

primidone

Answer 9

POST synaptic GABA promoter

Question 10

• clonazepam
• lorazepam
• diazepam
• clobazam

Answer 10

POST synaptic GABA promoter

- potentiate GABA binding by opening Cl-channels with greater frequency

Question 11

ethosuximide

Answer 11

pre-synaptic Ca T-type channel blocker (used for absence seizures!)

Question 12

zonisamide

Answer 12

pre-synaptic Ca T-type channel blocker (and Na-channel blocker)

Question 13

• levtiracetam

- bivatacetam

Answer 13

synaptic vesicle 2A protein blockers (SV2A)

Question 14

gabapentin

Answer 14

a2 Ca-channel blocker

Question 15

pregabalin

Answer 15

a2-channel blocker

Question 16

ezogabine

Answer 16

K-channel opener (both pre and post-synaptic)

Question 17

what are the 3 different MOA’s of topiramate?

Answer 17

1. Na-channel blocker
2. AMPA-r blocker
3. POSTsynaptic GABA promoting agent

Question 18

what are the 3 different MOA’s of valproic acid?

Answer 18

1. Na-channel blocker
2. GABA-T inhibitor (presynaptic GABA promoter)
3. Ca T-type channel blocker

Question 19

what are the 2 syndromes that CBD (Epidiolex) is approved to treat?

Answer 19

• Dravet syndrome
• Lennox-Gastaut syndrome

two very rare, hard to treat forms of epilepsy
- MOA unknown

Question 20

what are the 2 broad class-wide warnings of all AED’s?

Answer 20

1. abrupt withdrawal of antiepileptic medication may precipitate status epilepticus
2. suicidal behavior and ideation

Question 21

which AED is a well-known inducer of CYP-450 enzymes and has zero-order pharmacokinetics (taking higher doses makes the drug stay in their system longer)?

Answer 21

phenytoin

Question 22

what are the select toxicities of phenytoin (Na-channel blocker)?

Answer 22

• gingival hyperplasia

- hypocalcemia/vit D deficiency/osteoporosis

Question 23

what are the select toxicities of carbamazepine?

Answer 23

leukopenia/neutropenia/thrombocytopenia

Question 24

which drug is a less-potent CYP450 inducer than carbamazepine, due to formation of an alternative active metabolite?

Answer 24

oxcarbazepine

- less-otent CYP450 inducer

Question 25

what drug causes permanent progressive, bilateral vision loss, and is prescribe able only via a REMS program

Answer 25

vigabatrin NOTE: discontinue after 3 months if no effective response

Question 26

what 3 AED drugs a CPY450 inducers?

Answer 26

carbamazepine, phenytoin, phenobarbital

Question 27

what medications do AED (CYP450) inducers increase the clearance of?

Answer 27

- hormonal contraceptives -> elevated risk of pregnancy!! - warfarin -> elevated risk for arterial/venous thrombosis - HIV medications -> elevated risk of HIV replication

Question 28

valproid acid and lamotrigine inhibit conjugation of drugs by UGT, causing accumulation of what?

Answer 28

``` parent drugs (less metabolite) - especially when used together ```

Question 29

phenytoin, carbamazepine and phenobarbital induce conjugation of drugs by what non-CYP450 mechanism, causing a reduction of parent drug (increasing metabolites)?

Answer 29

UGT NOTE: not used as 1st line treatment

Question 30

what is the first line therapy for status epilepticus?

Answer 30

first IV: - lorazepam - diazepam (then addition lorazepam)

Question 31

what is first like therapy for status epilepticus if no IV access?

Answer 31

midazolam

Question 32

what is first line therapy in second IV for status epilepticus?

Answer 32

- fosphenytoin - phenytoin - valproid acid - levetiracetam

Question 33

what is the secondary therapy for status epilepticus?

Answer 33

- repeat fosphenytoin if not given previously - intubation, BP monitor - prepare for continuous midalozam or propofol infusion

Question 34

what are the 2 AMPA-r blockers?

Answer 34

topiratamate | perampanel

Question 35

what are the 2 GABA-T enzyme inhibitors?

Answer 35

vigabatrin | valproic acid

Question 36

where are GAT-1 channels located?

Answer 36

on presynaptic GABA neurons and astrocytes

Question 37

what is primidone converted to in the body?

Answer 37

phenobarbital

Question 38

are barbiturates GABA independent or dependent?

Answer 38

INdependent, which is why overdose is so much more likely than benzos (which are GABA-dependent)

Question 39

what is the ONLY drug used for absence seizures?

Answer 39

**ethosuximide** KNOW - only limits excitation of PRE-synaptic GABA neuron Ca-channels

Question 40

what is the synnergistic combo that both Hon and Segars wanted us to know for AED meds?

Answer 40

valproic acid and lamotigrine | - inhibit conjugation of drugs by UGT, causing accumulation of parent drug