Antiseizure drugs Flashcards Preview

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Flashcards in Antiseizure drugs Deck (10):
1

Phenytoin, fosphenytoin

  • Cyclic ureide
  • MOA
    - block high-frequency firing of neurons through action on VG Na+ channels
    - decrease synaptic release of glutamate
  • Kinetics
    - zero-order
    - highly bound to plasma proteins
    - no active metabolites
    - dose-dependent elimination, t1/2 12-36h
    - fosphenytoin is for IV, IM routes
  • Clinical
    - generalized tonic-clonic seizures, partial seizures
  • Tox, int.
    - tox: diplopia, ataxia, gingival hyperplasia, hirsutism, neuropathy
    - int: any drug that binds to plasma proteins 

2

Phenobarbital (cyclic ureide)

  • MOA
    - enhances phasic GABAA receptor responses, reduces excitatory synaptic responses 
  • Kinetics
    - nearly complete absorption, not significantly bound to plasma proteins
    - peak conc in 0.5-4h, no active metabolites, t1/2 varies from 75-125h 
  • Clinical
    - generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus
  • Tox, int. 
    - tox: sedation, cognitive issues, ataxia, hyperactivity
    - int: so many drugs 

3

Ethosuximide

  • Cyclic ureide
  • MOA
    - reduces low-threshold Ca2+ currents (T-type)
  • Kinetics
    - well absorbed orally, peak levels in 3-7h, not protein-bound, completely metabolized to inactive compounds, t1/2 typically 40h
  • Clinical
    - absence seizures 
  • Tox, int.
    - tox: nausea, headache, dizziness, lethargy
    - int: valproate, phenobarbital, phenytoin, carbamazepine, rifampacin

4

Carbamazepine

  • Tricyclic
  • MOA
    - blocks high-frequency firing of neurons through action on VG Na+ channels
    - decreases synaptic release of glutamate
  • Kinetics
    - well absorbed orally, peak levels in 6-8h, no significant protein binding, metabolized in part to active 10-11-epoxide
    - t1/2 8-36h 
  • Clinical
    - generalized tonic-clonic seizures, partial seizures 
  • Tox, int. 
    - tox: nausea, diplopia, atazia, hyponatremia, headache
    - int: many

5

Diazepam

  • MOA
    - potentiates GABAA responses
  • Kinetics
    - well absorbed orally, rectal administration gives peak conc in approx 1h with 90% bioavailability
    - IV for status epilepticus 
    - highly protein bound, extensively metabolized to several active metabolites, t1/2 2d
  • Clinical
    - status epilepticus, seizure clusters 
  • Tox, int.
    - tox: sedation
    - int: additive with sedative-hypnotics

6

Clonazepam

  • MOA
    - potentiates GABAA responses
  • Kinetics
    - >80% bioavailability, extensively metabolized but no active metabolites, t1/2 20-50h 
  • Clinical
    - absence seizures, myoclonic seizures, infantile spasms
  • Tox, int. 
    - tox: sedation
    - int: additive with sedative-hypnotics

7

Vigabatrin

  • GABA derivate
  • MOA
    - irreversibly inhibits GABA-transaminase
  • Kinetics
    - 70% bioavailable, not bound to plasma proteins, not metabolized
  • Clinical
    - partial seizures, infantile spasms 
  • Tox, int. 
    - tox: drowsiness, dizziness, psychosis, visual field loss
    - int: minimal 

8

Valproate

  • MOA
    - blocks high-frequency firing of neurons, modifies amino acid metabolism
  • Kinetics
    - well absorbed from several formulations, highly bound to plasma proteins, extensively metabolized, t1/2 9-16h
  • Clinical
    - generalized tonic-clonic seizures, partial seizures, generalized seizures, absence seizures, myoclonic seizures
  • Tox, int.
    - tox: nausea tremor, weight gain, hair loss, teratogenic, hepatotoxic
    - int: many

9

Lamotrigine

  • MOA
    - prolongs inactivation of VG Na+ channels
    - acts presynaptically on VG Ca2+ channels, decreasing glutamate release
  • Kinetics
    - well absorbed orally, no significant protein binding, extensively metabolized but no active metabolites, t1/2 25-35h
  • Clinical
    - generalized tonic-clonic seizures, generalized seizures, partial seizures, absence seizures
  • Tox, int.
    - tox: dizziness, headache, diplopia, rash
    - int: many

10

Levetiracetam

  • MOA
    - action on synaptic protein SV2A
  • Kinetics
    - well absorbed orally, not bound to plasma proteins, metabolized to 3 inactive metabolites, t1/2 6-11h
  • Clinical
    - generalized tonic-clonic seizures, partial seizures, generalized seizures
  • Tox, int.
    - tox: nervousness, dizziness, depression, seizures
    - int: rare