Antiepileptics Flashcards
What class is Phenytoin
Sodium channel blocker
Phenytoin is used for what types of seizures
GTC and partial seizures
Side effects of phenytoin
Nause, loss of appetite
Poor coordination, drowsiness
Hirsutism, gums hyperplasia
BM suppression
Osteoporosis
TEN - HLAB 1502
Teratogenic
Phenytoin induces which enzyme
3A4 and 2C9
What drugs increase phenytoin levels
Warfarin and trimetoprim
Describe the metabolism and elimination of phenytoin
Mixed-order kinetics. Upon saturation, small increase in dose may lead to large increase in drug concentration
What type of seizures do carbamazepine prevent
GTC and partial seizures
NOT for myoclonic
Mechanism of action of carbamazepine
Binds preferentially to inactive form of sodium channel, inhibit entry of sodium and suppress AP
Side effects of carbamazepine
NV, constipation
poor coordination, drowsiness
Decreased WBC and platelet
Hyponatremia, SIADH
TEN and SJS - HLAB 1502
Teratogenic
Drugs decreasing metabolism of carbamazepine
erythromycin, cimetidine, CCB
Carbamazepine is an inducer of…
CYP 450 (increase clearance of many drugs), strong inducer and it’s own plasma half-life is shortened to 15H when given repeatedly
Indications of sodium valproate
GTC, partial seizures, absence seizures
Side effects of sodium valproate
NV, constipation
poor coordination, drowsiness
hepatotoxicity
decreased platelets, bleeding
pancreatitis
suicidal behaviour
teratogenic
Sodium valproate is an inducer or inhibitor?
Inhibitor of 2C9, glucuronyl transferase and epoxide hydrolase + highly protein bound
MOA of valproate
Blocks voltage-gated sodium channels, increased brain levels of GABA
GABA system enhanced by?
1) binding directly to GABA-A receptors - BZD, barbiturates
2) inhibit reuptake of GABA - tiagabine
3) inhibit metabolism by GABA transaminases - vigabatrine
4) GAD modulator - gabapentin, valproate?
What drugs are glutamate blockers
AMPA - topiramate
NMDA - felbamate, levetiracetam
How do glutamate blockers work?
Drug binds to glutamate receptors and block it, prevents flow of calcium and sodium ion into cell resulting in inhibition
Monotherapy of new AEDs
topiramate, oxcarbazepine and lamotrigine
AEDs to use in concomitant migraine
valproate, gabapentin, topiramate
AEDs to avoid in young women
Valproate (high teratogenecity)
Phenytoin (cosmetic effects - hirsutism)
AEDs that are hepatic enzyme inducers
Phenytoin
Carbamazepine
Barbiturates
Oxcarbazepine
Topiramate
First line AEDs choice
carbamazepine, phenytoin, valproate
When are AED level tested
AED level help clinical management under following clinica indications:
1) assessment of compliance in refractory epilepsy
2) assessment of symptoms due to AED toxicity
3) titration of phenytoin dose
How to assess AED treatment working
1) Seizure frequency - ensure to assess if it is truly a seisure or other ddx (syncope, TIA, hypogly etc..)
2) Assess if there are any risk of breakthrough seizures:
- non compliance to AEDs
- DDI with other medications that lower AED levels
- alcohol abuse
- sleep deprivation
- concurrent illness
Risks for breakthrough seizures
Non-compliance to AEDs
Interactions with AEDs that lower AED serum level
Alcohol abuse
Sleep deprivation
Concurrent illness
When would you check patients after titrating AEDs?
5 half-life to new steady state so 1 month later
