Anticonvulsant Drugs Flashcards
phenytoin (Dilantin)
fosphenytoin (Cerebyx)
Cyclic ureide
MOA: blocks and prolongs inactivated state of voltage-gated Na+ channels–>block persistent Na+ current–> block high-frequency firing of neurons
Decreases synaptic release of glutamate
Enhances release of GABA
Prevents seizure propagation
Use: generalized tonic-clonic seizures (grand mal), partial seizures
Pharmacokinetics: poorly soluble, highly bound to plasma proteins, metabolized by liver, induces P450, 0 order kinetics
Side effects: depression nystagmus, diplopia, ataxia, gingival hyperplasia, megoblastic anemai, neuropathy, cardiac dysrhythmias
Drug interactions: other anticonvulsants
carbamazepine (Tegretol)
oxacarbazepine (Trileptal)
Tricyclics
MOA: blocks voltage gated Na+ channels–>inhibit high frequency repetitive firing of neurons
Decrease presynaptic release of glutamate
Pharmacokinetics: absorbed orally, metabolized by liver, induces P450s
Use: general clonic-tonic seizures (grand mal), partial seizures, trigeminal neuralgia (carbamazepine=drug of choice), bipolar disorder
Side effects: depression, nausea, diplopia, ataxia, leukopenia, osteomalacia, increase ADH, megablastic anemia, headache
Teratogenic: spina bifida, cleft lip and palate
Drug interaction: other anticonvulsants
phenobarbital (Luminal)
Cyclic ureide
MOA: increases duration of opening of Cl- channel–>enhances GABAa receptor responses
Block Na+ and Ca2+ currents–>decrease excitatory synaptic response
Pharmacokinetics: absorbed, not bound to plasma proteins, no active metabolite
Use: grand mal, partial, myoclonic, gneralized, and neonate seizures; status epilepticus
Side effects: sedation, cognitive issues, ataxia, hyperactivity
Interactions: other anticonvulsants
primidone (Mysoline)
Cyclic Ureide
MOA: like phenytoin but converted to phenobarbital
Blocks and prolongs inactivated state of voltage-gated Na+ channels–>block persistent Na+ current–> block high-frequency firing of neurons
Decreases synaptic release of glutamate
Enhances release of GABA
Prevents seizure propagation
Pharmacokinetics: orally absorbed, not bound to plasma proteins, 2 active metabolites–phenobarbital and phenylethylmalonamide
Use: grand mal, partial seizures
Side effects: sedation, cognitive issues, ataxia, hyperactivity
Drug interactions: other anticonvulsants
ethosuximide (Zarontin)
Cyclic ureide
MOA: block presynaptic Ca2+ influx through T-type channels–>decrease low threshold currents–>block high-frequency firing of neurons
Pharmacokinetics: orally absorbed, not protein bound, metabolized to inactive compound
Use: absence seizures (petit mal)–drug of choice
Side effects: GI distress, headache, dizziness, hyperactivity
Drug interactions: valproic acid, phenobarbital, phenytoin, carbamazepine, rifampicin
valproate/valproic acid (Depakene)
Antiseizure drug
MOA: reduce presynaptic Ca2+ influx through T-type channels–>decrease low threshold currents–>block high frequency firing neurons
Inhibition of GABA transaminase
Modifies amino acid metabolism
Pharmacokinetics: well absorbed, highly bound to plasma proteins, induces P450s
Use: grand mal, partial, generalized, absence, and myoclonic seizures; bipolar disorder, migraine prophylaxis
Side effects: GI distress, tremor, weight gain, hair loss, teratogenic
Hepatotoxic: rare but NOT recommended for
diazepam (Valium)
lorazepam (Ativan)
clonazepam (Klonopin)
Benzodiazepines/Centrally acting skeletal muscle relaxants
MOA: Potentiate GABAa responses by increasing frequency of Cl- channel openings
Pharmacokinetics: absorbed orally, highly protein bound, IV sometimes
Use: status epilepticus ( preferred initial agent), seizure clusters
Side effects: sedation
Drug interactions: minimal
gabapentin (Neurontin)
pregabalin (Lyrica)
vigabatrin (Sabril)
GABA derivatives
MOA: inhibit presynaptic voltage-gated Ca2+ channels–>decreases synaptic glutamate release
Do not act directly on GABA receptors
Pharmacokinetics: not bound to plasma proteins
Uses: grand mal, partial, and generalized seizures; neuropathic pain (fibromyalgia)
Side effects: somnolence, dizziness, ataxia
Drug interactions: minimal
lamotrigine (Lamictal)
Antiseizure drug
MOA: blocks and prolongs inactivation of voltage-gated Na+ channels–>block rapid firing of neurons
Inhibits presynaptically voltage-gated Ca2+ channels
Decreases presynaptic glutamate release
Pharmacokinetics: absorbed orally, don’t bind plasma proteins, metabolized into active metabolites
Use: grand mal, partial, generalized, and absence seizures; bipolar disorder
Side effects: dizziness, headache, diplopia, nausea, somnolence, skin rash, Stevens-Johnson syndrome
Drug interactions: other anticonvulsants
tiagabine (Gabitril)
Antiseizure drug
MOA: block GABA reuptake in forebrain
Selective blockade of GABA transporter GAT-1 in neurons and glia–>increase extracellular GABA
Pharmacokinetics: well absorbed, highly bound to plasma proteins, not active metabolites
Use: partial seizures
Side effects: nervousness, dizziness, depression
Drug interactions: phenytoin, carbamazepine, phenobarbial, primidone
topiramate (Topamax)
Antiseizure drug
MOA: block voltage-gated Na+ channels, inhibit presynaptically voltage-gated Ca2+ channels, potentiate inhibitory actions of GABA
Pharmacokinetics: well absorbed, not bound to plasma proteins, not active metabolites
Use: grand mal, partial, generalized, and absence seizures; migraine
Side effects: somnolence, cognitive slowing, confusion, paresthesias
Drug interactions: phenytoin, carbamazepine, oral contraceptives, lamotrigine
baclophen (Lioresal)
Centrally acting skeletal muscle relaxant
MOA: GABAb agonist in spinal cord
Use: spasticity associated with MS ad spinal injury
felbumate (Felbatol)
Glutamatergic target antiseizure drug
MOA: blocade of NMDA receptors at postsynapse
