Antiseizure drugs Flashcards
What is the MOA of gabapentin?
Unknown but enhances GABAergic effects and blocks presynaptic calcium channels, which could decrease glutamate release
What is the MOA of phenytoin and carbamazepine?
Prolongs inactivated state of Na-channels by blocking a voltage gated sodium channel
What is the MOA of lamotrigine?
- Prolongs inactivated state of Na-channels by blocking a voltage gated sodium channel
- Inhibits excitatory neurotransmission by blocking glutamate release
- Blocks T-type calcium channels (absence seizures only)
What is the MOA of topiramate?
- Prolongs inactivated state of Na-channels by blocking a voltage gated sodium channel
- Inhibits excitatory neurotransmission by blocking AMPA
- Enhances inhibitory neurotransmission via GABA-A
What is the MOA of valproic acid?
- Prolongs inactivated state of Na-channels by blocking a voltage gated sodium channel
- Enhance inhibitory neurotransmission via GABA-T
- Blocks T-type calcium channels (absence seizures only)
What is the MOA of levetiracetam?
Targets excitatory glutamanergic synapse by blocking at the vesicle
What is the MOA of perampanel?
Targets excitatory glutamanergic synapse by blocking AMPA
What is the MOA of tiagabine?
Targets inhibitory GABAergic synapse via GAT-1 transporter
What is the MOA of barbituates and benzodiazepines?
Targets inhibitory GABAergic synapse via GABA-A
What is the MOA of ethosuximide?
Blocks T-type calcium channels and can be used in absence seizures only due to a single blockade
What antiseizure drugs are considered broad spectrum?
Valproic acid and lamotrigine
What are the clinical uses of phenytoin?
Any seizure type except absence seizures (effective against focal onset and generalized onset tonic-clonic seizures)
What are drug interactions with phenytoin?
- Induces CYP3A4 (increases metabolism of other drugs) so would decrease effectiveness of birth control or other antiseizure drugs like carbamazepine
- Caution w phenytoin dosage as it’s zero order and toxicity could occur easily
What are side effects seen with phenytoin?
- CNS: nystagmus, ataxia, diplopia, sedation
- Endocrine: osteomalacia w hypocalcemia
- Hematologic effects: megaloblastic anemia (folate deficiency)
- Misc: gingival hyperplasia, facial coarsening, hirsutism
What are contraindications with phenytoin?
Teratogenic–> can cause cleft lip and palate
What are clinical uses for carbamazepine?
- Any seizure type except absence seizures (effective against focal onset seizures with or without spread to bilateral tonic-clonic seizure)
- Trigeminal neuralgia (DOC)
- Bipolar disorders
T/F: You can start to see lower levels of carbamazepine if you take it for a while
True; this is due to it being an auto-inducer of its own metabolism
What are side effects seen with carbamazepine?
CNS: diplopia, ataxia, and drowsiness
Hypersensitivity: rash, steven johnson syndrome (BBW)
Hematologic: leukopenia and aplastic anemia (BBW)
Endocrine: Dilutional hyponatremia from ADH
What drug interactions are seen with carbamazepine?
There are many due to CYP450 induction and enhances the metabolism of drugs that are degraded by these enzymes
What are contraindications of carbamazepine?
Teratogenic–> cleft lip/palate and spina bifida
What are the clinical uses for ethosuximide?
Used only for absence seizures and is the drug of choice
What are side effects seen with ethosuximide?
GI: anorexia, n/v
CNS: sedation, dizziness, ataxia
What are clinical uses for valproic acid?
Any seizure states (including absence seizures), migraine prophylaxis, and bipolar disorders
What are side effects seen with valproic acid?
GI: n/v and weight gain
Liver: toxic so monitor LFTs
CNS: tremor, dizziness, sedation
Misc: alopecia
What are drug interactions for valproic acid?
Inhibits CYP2C9 so decreases metabolism of phenytoin and phenobarbital (can cause increased levels of these leading to toxicity)
WWhat are contraindications of valproic acid?
- Patients with liver disease
- Children (d/t increased risk of fatal hepatotoxicity)
- Teratogenic: spina bifida (BBW for pregnancy and contraception requirement)
What are the clinical uses of lamotrigine?
Any seizure state (including absence) but usually adjunct therapy + can be used for bipolar disorder
What are side effects with lamotrigine?
CNS: dipolpia, headache, ataxia
Hypersensitivity: skin rash (BBW) and steven johnson syndrome
What are the clinical uses of topiramate?
Any seizure type except absence seizures: effective against primary and secondary generalized tonic-clonic seizures; focal seizures
What are adverse effects of topiramate?
CNS: cognitive problems (memory and language difficulties), headache, fatigue, dizziness
Misc: weight loss
What is the combination of phentermine and topiramate used for?
Weight loss
What are drug interactions for topiramate?
Induces CYP3A and inhibits CYP2C19
What are contraindications of topirmate?
Teratogenic: cleft lip/palate
What are clinical uses of gabapentin?
- Focal onset seizures and focal onset seizures with spread to bilateral tonic-clonic seizures (adjunct therapy)
- Neuropathic pain
How do the pharmacokinetics of gabapentin affect dosing regimens?
The transport is saturable so its bioavailability decreases with dose: to increase the dose patients have to often take this more often (multiple times a day)
What are side effects with gabapentin?
CNS: sedation, dizziness, ataxia
Misc: weight gain
What is the clinical use for tiagabine?
Focal onset seizures and often used as adjunct therapy
What are side effects seen with tiagabine?
CNS: sedation and dizziness
What are clinical uses for diazepam and lorazepam?
Treatment for status epilepticus in emergency seizures over 5 minutes
What are the clinical uses for phenobarbital and pentobarbital?
Treatment for status epilepticus
What are side effects seen with diazepam and lorazepam?
Sedation, motor impairment, amnesia, physical dependence
What are side effects seen with phenobarbital and pentobarbital?
Sedation (limiting), drowsiness, cognitive issues, and ataxia
What are the treatment guidelines for status epilepticus?
IV lorazepam (or diazepam or midazolam) then wait one minute. If there is no response, additional lorazepam. Even if the seizure stops give nonbenzo seizure drug (fosphenytoin)
What are clinical uses for levetiracetam (keppra) and brivaracetam?
Any seizures and FDA approved for adjunctive therapy
What are side effects seen with levetiracetam and brivaracetam?
Minor CNS: sedation, depression
What is the clinical use for perampanel?
Any seizure and approved for primary or adjunctive therapy
