Anti-epileptic Drugs Flashcards
Treatment of focal seizures, generalized tonic-clonic seizures
Blocks tetanic firing by increased sodium channel inactivation (decreasing Na+ influx) and therefore reducing neurotransmitter release
Inhibits release of excitatory amino acids by acting on presynaptic voltage gated calcium channels to decrease Ca2+ influx
Half-life reduced by phenytoin, carbamazepine
Half-life prolonged by valproate
Rash most common in children
Lamotrigine
Treatment of focal seizures, generalized tonic-clonic seizures
Synaptic vesicle protein 2A (SV2A) protein ligand
Inhibits calcium-dependent excitatory amino acid transmitter release by interfering with fusion of vesicles
Toxicities: dizziness, somnolence, weakness, dermatological conditions, behavioral changes, adverse cognitive effects
No clinically significant drug-drug interactions
Levetiracetam
Treatment of focal seizures, generalized tonic-clonic seizures
Blocks tetanic firing by increased sodium channel inactivation (decreasing Na+ influx) and therefore reducing neurotransmitter release
Potentiates GABA response
Tricyclic antidepressant used to treat bipolar disorder and trigeminal disorder
Highly protein bound
Active metabolite
Hepatic metabolism
Toxicities: diplopia, nystagmus, dizziness, ataxia, aplastic anemia, blood dyscrasias, rash, toxic epidermal necrolysis
Drug-drug interactions
Carbamazepine
Treatment of focal seizures, generalized tonic-clonic seizures
Similar to carbamazepine but with improved toxicity profile due to less induction of hepatic enzymes
Oxcarbamazepine
Treatment of generalized seizures (absence and myoclonic seizures)
Inhibits T-type Ca2+ channel activity in thalamic neurons
Not protein bound
Metabolized by microsomal enzymes
Toxicities: gastric pain, nausea, vomiting
Considered safe drug
Ethosuximide
Treatment of generalized seizures (absence seizures)
Blocks tetanic firing by increased sodium channel inactivation (decreasing Na+ influx) and therefore reducing neurotransmitter release
Reduces T-type Ca2+ channel activity
Increases GABA levels by inhibiting breakdown
Also used in focal dyscognitive seizures
Well absorbed, highly protein bound, active drug may be metabolite
Toxicities: nausea, vomiting, GI distress, little sedation, hepatotoxicity
Valproate
Treatment of status epilepticus
Increases affinity of GABA for GABAa receptor
Well-absorbed, widely distributed, metabolized by hepatic microsomal enzymes
Sedative, tolerance leads to withdrawal limiting utility in treating epilepsy
Prolonged status epilepticus can lead to resistance due to changes in GABAa subunit expression
Diazepam
Treatment of focal seizures, generalized tonic-clonic seizures, status epilepticus
Blocks tetanic firing by increasing sodium channel inactivation (decreasing Na+ influx) and therefore reducing neurotransmitter release
Good oral absorption, dose dependent
Time to peak varies between patients
Non-linear relationship between dose and plasma level due to shift from first order kinetics at low doses to zero order at higher doses
Highly protein bound and reversibly stored in fat
Metabolized by hepatic microsomal enzymes
Toxicities: cardiac arrhythmias, CNS depression, headache, loss of balance, gingival hyperplasia, rash, hirsutism
Phenytoin
Adjuvant therapy for focal seizures with or without secondary generalization
Binds voltage gated Ca2+ channel subunit to decrease glutamate release
Inhibits GABA transaminase (GABA-T) but maybe not at physiological concentrations
Not protein bound or metabolized
Few drug-drug interactions but does interact with cimetidine and antacids
Also used for chronic pain management
Gabapentin
Adjunct therapy for refractory focal dyscognitive seizures
Inhibits GABA-T
Reduces plasma concentrations of primidone
Toxicities: drowsiness, dizziness, weight gain
Potentially irreversible concentric visual field deficit, restricted distribution program in effect
Also used in infantile spasms
Vigabatrin
Treatment of focal seizures and generalized tonic-clonic seizures
Blocks tetanic firing by increased sodium channel inactivation (decreasing Na+ influx) and therefore reducing neurotransmitter release
Inhibits kainate and/or AMPA receptors
Enhances actions of GABA
Also used as prophylaxis and treatment for migraines
Toxicities: somnolence, fatigue, weight loss, nervousness, cognitive impairment
Topiramate
Adjuvant therapy for focal seizures and generalized tonic-clonic seizures
Primary site of action is the sodium channel, also acts on T-type voltage-gated Ca2+ channels
Fairly broad spectrum, also works in absence seizures, myoclonic seizures, and infantile spasms
Toxicities: drowsiness, cognitive impairment, potentially serious skin rashes
Does not interact with other antiseizure drugs
Zonisamide
