Seizures

Question 1

First line for focal seizures

Answer 1

Lamotrigine

Question 2

First line for generalized seizures

Answer 2

Valproate - unless pregnant!!

Question 3

Gabapentin PK

Answer 3

Requires active transport

Limit to 1,200mg per dose b/c saturable

Question 4

Main clinically significant interaction PK interaction in terms of absorption

Answer 4

Phenytoin and enteric feeding

Question 5

Drugs clinically important in terms of protein binding (>90%):

Answer 5

Phenytoin*
Valproate
Diazepam
Tiagabine
Perampanel

Question 6

Why should you check phenytoin levels regularly?

Answer 6

Narrow therapeutic range, but also…

accumulation leads to rapid serum level changes even with small dose adjustments within the therapeutic window.

Question 7

Why should you check carbamazepine levels regularly upon initiation?

Answer 7

Autoinduction: levels will be higher within first week or so than they will after that, as autoinduction increases it’s metabolism.

Question 8

What is the the main route of metabolism of AEDs?

Answer 8

Oxidation by Cytochromes.

- Most notable: 2C9, 2C19, and 3A4.

Question 9

Possible clinical scenarios with AEDs and other drugs:

Answer 9

Adding inducer-AED to statins; decrease statin.
Adding new med to inducer-AED; ineffective birth control.
Removal of inducer: warfarin goes nuts.

Question 10

Inducer/inhibitor timing

Answer 10

Inducers = slow to take effect
Inhibitors = rapid effects

Question 11

Broad spectrum inducers

Answer 11

CBZ
Phenytoin
Phenobarbital/Primidone

Question 12

Selective 3A4 inducers

Answer 12

Felbamate
Topiramate
Oxcarbazepine
Eslicarbazepine

Question 13

UGTs involved in AED metabolism

Answer 13

UGT1A9 - valproate
UGT2B7 - valproate and lorazepam
UGT1A4 - lamotrigine

Question 14

Inhibitors

Answer 14

Valproate - UGT and 2C19
Topiramate/Oxcarbazepine - 2C19
Felbamate - 2C19

Question 15

AEDs that are renally cleared

Answer 15

Gabapentin
Pregabalin
Levetiracetam
Lacosamide (1/2)
Eslicarbazepine (1/2)

Question 16

AED most related to rash-like SE’s:

Answer 16

Lamotrigine!

Question 17

Most common SE of AEDs

Answer 17

Neurologic/Psychiatric effects

- sedation, unsteadiness, tremor, vission problems, etc.

Question 18

Less common SEs of AEDs

Answer 18

GI - valproic acid
Lab changes
- hyponatremia - carbamazepine and related
- Increase LFTs
- Leukopenia - carbamazepine
- Thrombocytopenia - valproate
Weight gain - valproate, gaba/pregaba, CBZ a little
Weight loss - felbamate, zinisamide?, topiramate

Question 19

Aplastic anemia / agranulocytosis AED SE with:

Answer 19

Felbamate

Question 20

Hepatic failure AED SE with:

Answer 20

Felbamate

Question 21

Neuropathy / Cerebellar syndrome AED SE with:

Answer 21

Phenytoin

Question 22

Facial coarsening, hirsutism, gingival hyperplasia with:

Answer 22

Phenytoin

Question 23

Treatment recommendations for the elderly:

Answer 23

Use the new drugs
Focus on tolerability
Lamotrigine a good option

Question 24

Treatment recommendations for kids:

Answer 24

Avoid valproate - hepatotoxicity
Avoid lamotrigine - rash
May need higher doses b/c of rapid metabolism

Question 25

Treatment recommendations for women:

Answer 25

Caution inducers with oral contraceptives.
Teratogenicity a problem.
- All drugs class C or D, but may need them.
Breastfeeding - okay!
- Except barbiturates and benzos
Bone Health - can be a problem
- Switch to lamotrigine

Question 26

Status Epilepticus in general

Answer 26

Massive seizure, can leave permanent deficits.
Treat early and aggressively with IV AEDs.
Begin treatment if seizure duration persists > 5 minutes

Question 27

FDA approved therapy for home treatment of Status Epilepticus:

Answer 27

Rectal diazepam gel - really just for kids

Question 28

Status Epilepticus treatment

Answer 28

Step 1 - IV lorazepam
Step 2 - IV phenytoin/fosphenytoin
If refractory - IV midazolam or propofol