IC7 Seizure & epilepsy II Flashcards
What is the MOA of carbamazepine?
It is a sodium channel blocker.
What is carbamazepine used for?
It is used for:
1. Epilepsy
2. Neuropathic pain
3. Bipolar disorder
What are the 4 ADRs of carbamazepine?
- Drowsiness, dizziness, N&V
- Blood dyscrasia
- Hyponatremia
- Hypersensitivity*
What are the most severe hypersensitivity reactions of carbamazepine?
- SJS
- TEN
Which race has higher risk of carbamazepine induced hypersensitivity?
Asians have 10x higher risk than Caucasians.
This is due to the presence of HLA-B*1502
Apart from HLA-B*1502, what other allele have a wider range of hypersensitivity reactions with carbamazepine?
HLA-B*3101
In SG, which allele is mandatory for testing before starting pt on carbamazepine?
HLA-B*1502 testing is mandatory before starting pt on carbamazepine.
HLA-B3101 is optional. if pt has HLA-B1502, we still try to avoid using carbamazepine & use an alternative medcation.
If a patient has HLA-B*1502 and is on carbamazepine for >3 months with no severe ADR, what should we do?
Allow pt to continue on therapy as it is less likely that it will cause any severe ADRs.
What are some alternatives to carbamazepine in epilepsy treatment?
Levetiracetam, valproate, topiramate
What are the 1st generation antiseizure medications (ASM) that we need to know?
- Carbamazepine
- Phenytoin
- Phenobarbital
- Sodium valproate
For the 1st generation ASM, what are the common similarities that exist?
- High / low protein binding?
- Hepatically or renally cleared
- Do all of them have drug drug interactions?
For all 4 first generation drugs (CBZ, PB, PHT, VPA) that we need to know:
- They all have high protein binding, except phenobarbital with 50% protein binding
- They are all largely hepatically cleared
- They all have DDIs
What are the 2nd generation antiseizure medications that we need to know?
- Levetiracetam
- Topiramate
- Lamotrigine
- Clobazam
For 2nd gen ASM, what are the common similarities that exist?
(Levetiracetam, topiramate, lamotrigine, clobazam)
- High / low protein binding?
- Hepatically or renally cleared
- Do all of them have drug drug interactions?
Protein binding:
- Levetiracetam & topiramate have low protein binding
- Lamotrigine has moderate protein binding (50%)
- Clobazam have high protein binding
Renally or hepatically cleared:
- Levetiracetam (66%), topiramate (55%), clobazam (90%) are renally cleared
- Lamotrigine is 100% hepatically cleared
DDI:
- Levetiracetam has no DDI
- Lamotrigine has a few DDI
- Topiramate DDI is dose dependent
- Clobazam has DDI
What are the MOAs for all the 1st and 2nd generation medications that we need to know?
1st Gen:
1. Carbamazepine
2. Phenytoin
3. Phenobarbital
4. Sodium valproate
2nd Gen:
1. Levetiracetam
2. Topiramate
3. Lamotrigine
1st Gen:
1. Carbamazepine - Na+ channel blocker
2. Phenytoin - Na+ channel blocker
3. Phenobarbital - Ca2+ channel blocker
4. Sodium valproate - inhibits GABA, Na+ & Ca2+ channels
2nd Gen:
1. Levetiracetam - presynaptic SV2A release modulator
2. Topiramate - Na+ channel blocker
3. Lamotrigine - Na+ channel blocker
Which drug is the GOLD standard for focal onset epilepsy?
Focal onset seizures aka simple partial seizures - a seizure that happens while a person is awake, alert and aware of what is going on.
Carbamazepine
What are first line drugs used in GTC seizures?
- Carbamazepine
- Lamotrigine
- Sodium valproate
What is the first line drug used in tonic or atonic?
Sodium valproate
What are the 1st line drugs to use in absence seizures?
- Lamotrigine
- Sodium Valproate
What are the 1st line drugs to use in myoclonic seizures?
- Levetiracetam
- Sodium valproate
- Topiramate
What are the 1st line drugs for focal seizures?
- Carbamazepine
- Lamotrigine
- Levetiracetam
- Sodium valproate
Can you name which ASM are inducers or inhibitors of CYP enzymes / transporters?
1st gen:
Carbamazepine -
Phenobarbital -
Phenytoin -
Sodium valproate -
2nd gen:
Lamotrigine -
Levetiracetam -
Topiramate -
Clobazam -
1st gen:
Carbamazepine - inducer
Phenobarbital - inducer
Phenytoin - inducer
Sodium valproate - inhibitor
2nd gen:
Lamotrigine - inducer
Levetiracetam - no effect , hence no DDI
Topiramate - CYP3A4 inducer & CYP2C19 inhibitor
Clobazam - inhibitor
Note that sodium valproate & clobazam the only inhibitors.
The rest are all inducers.
Topiramate is the only drug that is both an inducer and inhibitor.
What are the 4 classes of drugs that have DDIs w ASMs?
- Antidepressants & antipsychotics
- Immunosuppressive therapy
- Antiretroviral therapy
- Chemotherapeutic agents
What are the different dosage forms for phenytoin?
- Oral suspension
- Capsules
Must we space apart enteral feeds & phenytoin? If yes, how long must we space them apart for?
Yes, we must space apart enteral feeds and phenytoin.
They are to be spaced apart every 2 hours.