Lecture 19 - Anti-Epileptic Drugs Flashcards
what is the goal of AED?
Decrease the frequency and/or seizures in people with epilepsy
Not curative
considerations for selection of the right AED?
Simplest regiment monotherapy better than poly Minimize side effects Cost Compliance
Mechanisms of sz – what is meant by weighted inhibtion ?
GABA interneurons inhibitng the surrounding neurons of an excitatory pathway; leading to high fidelity of the excitatory pathway
Primary mechanism (Channel) targetted for treatment of partial/secondary generlized sz?
Inactivation of an aberrantly activated Na Channel (Na channel which has lost refractory period)
Drugs which target Na Channels?
are they older or new generation?
Phenytoin – older gen
Carbarmezpine – older
Oxcarbazepine – new gen
Lacosamide – New Gen
Esclicarbaepine (Stedesa) – new
Phenytoin
Primary use? Mechanism? Pharmacology? Metabolism? Adverse effects?
Very effective and acts quickly – good for status epilepticus (not first line for Partial)
Mechanism – Na channel
Bound to albumin
Metabolism – p450; induces own metabolism; saturaiton kinetics at higher doses; can lead to toxicity
ataxia, nystagmus, incoordiatnion, confusion, hirsutism,
Gingival Hyperplasia
Carbamazepine
Mechanism?
use?
Metabolism? Metabolites?
Side effects?
First line for partial seizures, some use in tonic clonic
Suppresses the foci and the spread
Metabolism – inactivated by liver
Metabolites – 10-11 epoxy – neurotoxic
Side effects – Sedation, drowsiness, HA, dizziness, blurred vision
Oxcarbazepine
mechanism?
special use?
Metabolism?
Approved for children
Mechanism: Slow rate of Na Channel recovery
ALSO – agument K+ channels and block Ca2+ channels
Metabolism by the Liver -- some induction of p450s
Lacosamide
mechanism?
Unclear; changes the protein conformation of the Na channel and slows the rate of transmission
Esclicarbaepine (Stedesa
whats special about this drug?
metabolism?
dosing?
who should avoid it?
Pro-drug
No autoinduction
Decreases Oral Contraceptive availability
Once daily dosing
Drugs that effect GABA transmission/
what GABA receptor?
GABA a
Benzos
Barbituates
Misnomer drugs?
where do they actually work?
PreGabalin and GABApentin
Alpha 2 Delta 1 subunit of VG Calcium channel of excitatory neurons; Reduce the excitatory transmission (Glutamate)
Benzos
Mechanism?
clinical use?
side effcts
Keep the Channel open, but GABA has to be present to bind
Uses: Last line of choice; “sledge hammer”
Used to ablate seizures such as SE in acute setting
Sedation, dizziness, ataxia, drowsiness, and TOLERANCE
Barbituates
Mechanism?
clinical use?
side effcts
GABA mimetic and GABA potentiating
Side effects: heavy Sedation, cognitive effects, tolerance and withdrawal
Clinical use is decreasing
PreGabalin and GABApentin
Mechanism?
Clinical use?
side effects?
Mechanism – Alpha 2 Delta 1 subunit of VG Calcium channel of excitatory neurons; Reduce the excitatory transmission (Glutamate)
Clinical Use: add on therapies for tonic clinic and partial
Approved for children,
side effects – limited
rationale for using broad spectrum drugs for Tonic Clonic sz
Tonic Clonic Seizures –
Tonic phase: Acute and sudden loss of GABA
Clonic phase – GABA is restore but in alternating fashion
Drugs: Broader specturm drugs -- Drugs with more mechanisms of action
Name 5 broad spectrum drugs
Valproate Lamotrigine Zonisamide Topmirate Levatriacetam
Valproate
Pleoitropic mechanism?
who should this drug never be given to?
Inhibits T Type Calcium ChannelSlows rate of recovery for Na Channels
Increases GABA availability at the synapse (synthesis)
Pregnancy – Teratogenicity;
3 drugs that interact with Valproate/
Cabamazepine – -can induce each other’s Metabolism Inhibitors phenobarbitol metabolism –
Displaces Phenytoin from binding proteins – increasing toxicity
Lamotrigine
mechansims?
Metabolsim?
Slow rate of recovery of VG Na Channels; Inhibition of glutamate release; Inhibition of Ca 2+ channels;
Metabolism -- glucouronidse
Zonisamide
who should not take this drug?
mechanism?
whats good about its regimen?
uses?
Pleiotropic Mechanisms: Na Chnanles, T Type Calcium Channels, Reduction of Glutamate transmission
Absence sz – T type Calcium channel
Once daily dosing (long half life)
Contraindicated in Sulpha Allergic patients
Topmirate
mechanisms?
Ineffective for?
Ineffective at Absence sz
Antagonist at Glu Recetpors
GABA potentiaion
Na and Ca blockers
Carbonic anhydrase inhibitor – effecting pH
why is felbmate rarely used?
cognitive function
Blocks Glutamate Receptors – behvaioral effects
Liver failure
Aplastic Anemia
Levatriacetam (Keppra)
mechansim?
Modulation of the synaptic vesicles
Enhanced docking and release of GABA
