Antiseizure medications Flashcards
MOA of phenytoin
- Blockade of voltage gated Na+ channels
indication for phenytoin
- All except absence seizures
TDM of phenytoin
- Narrow therapeutic range (40-100uM)
- Saturation kinetics
- Non-linear relationship between dose and steady state plasma concentration
MOA of carbamazepine
- Blockade of voltage gated Na+ channels
indication for carbamazepine
- All except absence seizures
PK of carbamazepine
- CYP450 inducer
- Half-life of carbamazepine shortens with repeated dose
- Accelerates elimination of other drugs
Pharmacogenomics of carbamazepine
- In Asians: test for HLAB*1502 allele before commencing carbamazepine due to increased risk of SJS/TEN
MOA of sodium valproate
- Blockade of voltage gated Na+ and Ca2+ channels
- Inhibits GABA transaminase (an enzyme which breaks down GABA) increases GABA increased inhibition of neuron
indication of sodium valproate
all seizures
PK of sodium valproate
- Strongly bound to plasma protein
- Can displace other antiepileptics
- In combination therapy, since valproate can displace other antiepileptics, apparent free drug concentration will be higher than expected, dose adjust accordingly
ADR of ASM: dose related
Drowsiness, confusion, nystagmus, ataxia (movement coordination disorder),
slurred speech, nausea, unusual behaviour, mental changes, coma
ADR of ASM: Non dose related
Hirsutism, acne, gingival hyperplasia (gums become swollen and overgrown), folate deficiency, osteomalacia (bones getting softer), hypersensitivity reactions (including Stevens-Johnson syndrome)
MOA of diazepam
- Diazepam binds to regulatory site, not site where GABA binds at
- Enhances binding of GABA to GABA binding site
- Needs GABA to work
- Results in potentiating the influx of Cl- ions leading to hyperpolarisation of cell
Overdose of diazepam
- Severe respiratory depression, esp with alcohol
- Reversal: Flumazenil, a benzodiazepine antagonist
indication for levetiracetam
- 2nd line adjunctive therapy
- For partial onset seizures, myoclonic and primary generalised tonic clonic seizures
- Can be used as monotherapy for partial onset seizures in newly diagnosed epilepsy
PK for levetiracetam
- Highly soluble and permeable
- Low intra and inter subject variability
- Linear kinetics
- Route: Oral or IV
ADR for levetiracetam
Common
- Headache, vertigo, cough, depression, insomnia
Rare
- Agranulocytosis (decreased neutrophil count), suicide, delirium, dyskenisia (involuntary, erratic writhing of body)
MOA of lamotrigine
- Blocks voltage-gated sodium channels
- Inhibits release of glutamate
- Impedes sustained repetitive neuronal depolarization
Indication of lamotrigine
- 2nd line adjunctive therapy
- Can be used as monotherapy for generalised/partial onset seizures, including tonic clonic seizures
- Monotherapy of typical absence seizures
PK of lamotrigine
- Half life shorter in: induction of metabolism enzyme
o Children
o Co-administration with carbamazepine and phenytoin - Half life increased in: inhibition of metabolism enzyme
o Co-administration with valproate
ADR of lamotrigine
Common
- Headache, irritability, aggression, tiredness
Rare
- Agranulocytosis (decreased neutrophil count), hallucination, movement disorders, SJS/TEN, hepatic failure
Indication of topiramate
- Monotherapy for generalised/partial onset seizures, including tonic clonic seizures
- Prophylaxis of migraine (not treatment)
PK of topiramate
- Linear PK
- Route: Oral
- Long half life
- Renal CL
- Not a potent inducer of drug metabolising enzymes
ADR of topiramate
Common
- Depression, somnolence, fatigue, nausea, weight change
Rare
- Neutropenia, mania, tremor, transient blindness, SJS/TEN, hepatic failure
