Anti-epileptics Flashcards
Simple partial seizure?
• There is no loss of consciousness. • Often there is abnormal activity of a single limb or muscle group.
Complex partial seizure?
• There is loss of consciousness.
• Motor dysfunction may involve chewing
movements, diarrhea, urination.
Partial with secondarily generalized tonic-clonic seizure?
• The partial seizure evolves into a tonic clonic seizure with loss of consciousness.
Generalized tonic-clonic seizures?
- No evidence of localized onset.
- They may be convulsive or non-convulsive.
- There is immediate loss of consciousness.
Absent seizures (generalized)?
- Brief, abrupt and self-limiting loss of consciousness.
- The patient stares and exhibits rapid eye-blinking.
EEG - 3 Hz spike-and-wave pattern emerges abruptly and ceases after a few seconds
Mechanisms of seizures?
- trigger seizures - GABAa antagonists or glutamate agonist
2. inhibit seizure - GABAa enhancement or glutamate receptor antagonists
General MOA of anti-epileptic drugs?
- blockage of VG ion channels - VG Na+ and T-type Ca2+
2. modulation of synaptic transmission
Drugs that block VG Na+ channels?
- phenytoin
- carbamazepine
- Lamotrigine
- Zonisamide
- Phenobarital, valproate, topiramate?
**blocking VG Na+ channels blocks AP and therefore glutamate release
Drugs that block T-type Ca2+ channels?
Absence seizures involve oscillatory neuronal activity b/t thalamus and cortex that uses T-type Ca2+ channels.
Ethosuximide and Valproate inhibit the Ty-type Ca2_ channels and are therefore effective against absence seizures.
Drugs that enhance GABAergic neurotransmission postsynaptically?
Direct action on GABAa receptors..
- benzodiazepines
- barbiturates
- Topiramate
Drugs that enhance GABAergic neurotransmission presynaptically?
- inhibit GABA reuptake - Tiagabine
2. inhibit GABA degradation (GABA aminotransferase) - Vigabatrin
Drugs that reduce glutamatergic neurotransmission postsynaptically?
Phenobarbital an Topiramate - block glutamate receptors
Drugs that reduce glutamatergic neurotransmission presynaptically?
- Gabapentin and pregabalin - decrease glutamate release by blocking VG Ca2+ channels
- Levetiracetam - binds synaptic vesicle glycoprotein 2A (SV2A) - may affect release of glutamate and GABA - very unclear as to what it does other than binding to protein in the vesicle membrane
Drugs used in partial and secondarily Generalized tonic-clonic seizures?
- Carbamazepine -
- Oxcarbazepine-
- Levetiracetam
- Zonisamide
- Phenytoin -
- Valproate -
- Lamotrigine -
- Topiramate -
- Phenobarbital
All of the ones with (-) you can use for generalized tonic clonic seizures.
DOC of absence seizures?
Ethosuximide and Valproate
If on top of absence seizure there are tonic-clonic seizures - use Valproate NOT ethosuximide
If absence seizures are atypical (look like absence seizures, but lack of the 3Hz EEG pattern) - use Valproate over ethosuximide
**Lamotrigine is a newer drug that has recently become popular and may be effective
DOC of myoclonic seizures?
Valproate
2nd line - Topiramate
Adjuvant - Levetiracetam
Tx of atonic seizures?
Valproate and Lamotrigine
Tx of febrile convulsions?
If seizure lasts less than 15 minutes, tx is supportive. If seizure lasts more than 15 minutes, pharmacological tx is needed to prevent brain damage.
Tx - diazepam given IV or as a rectal solution
Tx of status epilepticus?
- IV lorazepam
- if seizure continues - IV phenytoin or Fosphenytoin (soluble with better bioavailability)
- if seizure continues - IV phenobarbital
- if seizure continues - general anesthesia with IV midazolam, propofol or barbiturates
Manage convulsive episode in non-epileptic pts?
Diazepam, Lorazepam, or phenobarbital
Tx of breakthrough seizure?
Seizures experienced by epileptic pt who is already on antiepileptic therapy.
Tx - diazepam rectal gel supplied as a pre-filled syringe
Which anti-epileptic drug induces cytochrome P450?
Carbamazepine
Phenobarbital
Phenytoin
Oxcarbazepine (similar to carbamazepine) - weak inducer
AE Valproate?
- Hepatotoxicity.
- Inhibits cytochrome P450.
- Inhibits metabolism of several drugs.
- Inhibits its own metabolism.
AE phenytoin?
- Diplopia, ataxia.
- Gingival hyperplasia****
- Coarsening of facial features in children.
- Hirsutism.
- Rash. Stevens-Johnson Syndrome.
- Zero order kinetics of elimination.
