ANTIEPILEPTIC AGENTS Flashcards
(20 cards)
epilepsy
condition characterized by seizures, in unpredictable manner, not associated with stimulus
seizure
episode of disordered, synchronized, rhythmic firing of brain neurons
causes of epileptic seizures
birth/ perinatal injuries blood clots head trauma metabolic disturbances drug/alcohol withdrawal neoplasia infection genetic hyperthermia in children visual stimuli
describe partial seizures
- COMPLEX PARTIAL (most frequent)
- partial consciousness with/without autonomic movements - SIMPLE PARTIAL
- conscious state not affected
- localised speech/sensory/motor defects
describe general seizures
- GRAND MAL
- loss of consciousness + rigid paralysis (TONIC state)
- rhythmic jerking movement of limbs (CLONIC state) - PETIT MAL (absence seizure)
- person suddenly exhibits a blank stare + unaware of surroundings
describe the effects of seizures on electroencephalographs
tonic - disorder (+) amplitdue
clonic - strokes of high rhythmic activity
petit mal - very rhythmic (+) amplitude
partial - distinctive - only effecting certain parts of brain
best treatment = detect whilst undergoing seizure
what does a PET scan do
measure areas of high metabolism
Kindling model
repeated electrical stimulation of amygdaloid nuclei = induce state where spontaneous seizures can occur
Kainate model
KAINATE + NMDA (agonists of glutamate receptors)
= produce spontaneous seizures and PAROXYSMAL DEPOLARISING SHIFT (PDS)
- suggesting overstimulation of glutamate receptors trigger seizures
what can induce PDS
penicilin
NMDA
Evidence that seizures can be induced by a deficit in INHIBITORY AMINO ACID NT
. GAGA receptor antagonists can induce seizures in animal model system
. drugs that have anti-seizure activities
= enhance activity of GABA (benzodiazepines)
OR
= inhibit GABA degradative pathways
= GABA reuptake inhibitors
3 mechanisms of anti-epileptics
- enhancement of GABA binding to receptor
- inhibition of Na+ channel
- inhibition of Ca2+ channel
primary antiepileptic drugs
- PHENYTOIN
- CARBAMAZEPINE
- VALPROATE
- ETHOSUXIMIDE
- BENZODIAZEPINES
- BARBITUATES
PHENYTOIN
Voltage-gated Na+ channel blocker -binds to inactive channels
•Grand mal and partial; not effective in petit mal
Treats status epilepticus
- Drug interactions: Competes for the metabolism of other drugs including oral anticoagulants
- Side effects: dizziness, nystagmus*, ataxia^, mental confusion, gingival hyperplasia, hirsutism, birth defects
where does PHENYTOIN bind
Phenytoin preferentially binds to the inactivation gate of Na2+ channels when they are in the closed position
CARBAMAZEPINE
- Derivative of Tricyclic Antidepressants
- Voltage-gated Na+ channel blocker + accentuation of adenosine-based inhibition of neuron firing
- Grand mal and partial; not effective in petit mal
• Side effects: drowsiness, dizziness, blurred vision,
ataxia, bone marrow depression (granulocytopenia
and/or aplastic anemia), birth defects
VALPROATE
- Voltage-gated Na+ channel blocker
- Works on all types of epilepsy, including petit mal
• Side effects: Nausea, vomiting, lethargy, hair
loss, teratogenic, hepatotoxicity
ETHOSUXIMIDE
• Derived from barbiturate structure
- Inhibition of T-type (thalamic) calcium channels
- Only useful for PETIT mal // worsen grand mal seizures
• Side effects: nausea, vomiting, anorexia, drowsiness, persistent hiccups
BENZODIAZEPINES and BARBITUATES
• bind to GABAA receptors = affinity of GABA for the receptor is enhanced
- Effective against all types (except petit mal)
- Epilepsy is only condition, other than GE, for which barbituates have a legitimate clinical use
• Sedation, general CNS suppression are problems, along with dependence + withdrawal
Other Antiepileptic Drugs
• Vigabatrin-a GABA analogue
= Irreversible inhibitor of GABA transaminase in astrocytes
- Lamotrigine = voltage-gated Na+ channel blocker
- Gabapentin = cyclic analogue of GABA - blocks Ca2+ channels in Dorsal Horn of SC = inhibits NMDA R and increases actions of CNS adrenergic neurons
