Pharmacology - Antiepileptic Drugs Flashcards
What are the molecular targets and actions of antiepileptic drugs?
- To limit excitability - voltage-gated Na and Ca channels and glutamate receptors
- To enhance inhibition of GABA system
Phenytoin
Carbamazepine
Oxcarbamazepine
Lamotrigine
These drugs all do what?
Antiepileptics and voltage-gated Na channels
Goal to stabilize the inactive state inhibiting recurrent depolarization
Blocking what channels decreases neuropathic pain?
Calcium channels
Ie Ethosuximide - T-type in thalamus
Gabapentin, Pregabalin - the high voltage type
Give the class: Felbamate
Glutamate receptor blocker
NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system
Give the class: Topiramate
Glutamate receptor blocker
Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system
Phenobarbitol and benzodiazepines activate what system in treating epilepsy?
GABA system
Give the class: Carbamazepine
Sodium channel blocker
MOA: Stabilize inactive conformation of Na channel
AEs: Dizzy, drunk, double vision, mild myelosuppression
Give the indications for Carbamazepine.
Better for complex partial epilepsy than primary generalized seizures
In addition to epilepsy, carbamazepine is also useful in treating:
Bipolar Affective disorder (also neuropathic pain)
More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain
What is the most important thing to remember about carbamazepine?
Autoinduction - it can induce metabolism of itself (requires dose increase after reaching steady state)
Heteroinduction - it can induce metabolism of other drugs
for example: contraceptive pill failure
Give the side effects: carbamazepine
Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
Give the class: Phenytoin
Voltage-gated Na channel stabilizer
Give the MOA: Phenytoin
Stabilize inactive conformation of Na channel
Give the indications: Phenytoin
Effective for tonic-clonic seizures of primary generalized epilepsy or partial onset and secondary generalized seizures
Less effective for absence (particular pediatric), myoclonic, atonic seizures
Give the side effects: Phenytoin
Long term side effects?
Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure
Long term: Cerebellar degeneration, peripheral neuropathy, osteoporosis
IV-Phenytoin is useful to treat what condition?
Status epilepticus
same with IV Valproate
How is oxcarbazepine different from carbamazepine?
Oxcarbazepine is less protein-bound, less autoinduction, fewer interactions, less toxic, has a longer half-life than carbamazepine
TEST QUESTION:
Lamotrigine is associated with what toxicity?
Dizziness
Sedation
Ataxia
Diplpia
AEs: rash (rarely Stevens-Johnson syndrome), slow initial titration is important
Is Lamotrigine indicated for use in children to treat epilepsy?
Yes
Effective for primary generalized epilepsy, partial complex epilepsy and secondary generalization, absence
Lamotrigine is NOT effective for what kind of seizures?
Myoclonic seizures
May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound
Give the indications for Lamotrigine.
Primary generalized epilepsies, absence seizures; indicated in children; bipolar disorder; neuropathic pain
Lamotrigine has synergistic action with what drug?
Depakote (valproic acid)
T/F: Lamotrigine can cause contraceptive failure.
True
Same with ALL voltage-gated sodium channel blockers - Phenytoin, Carbamazepine, Oxcarbamazepine
Give the class: Gabapentin and Pregabalin
GABA analog
Give the MOA of Gabapentin and Pregabalin.
Block presynaptic influx of Ca
Give the indications for Gabapentin and Pregabalin.
Adjunct for partial complex epilepsy; more commonly used for neuropathic pain
Ethosuximide is only effective against what kind of seizure?
Absence seizures
Give the side effects: Ethosuximide
Nausea (transient)
Sedation
Irritability
What is the half life of ethosuximide?
40-60 hours
T/F: Topiramate is active at the postsynaptic membrane.
True
Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system
Use: Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches
Side Effects: Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation and word finding difficulties
-Respiratory compensation from acidosis results in mild alkylosis, calcium ionization, and a sensation of tingling in fingers that can be alleviated with vitamin C
What drug is a good choice to treat partial onset and secondarily generalized seizures?
Levetiracetam
Give the class: Levetiracetam
Synaptic vesicle binder
Binds to vesicle protein 2 resulting in less neurotransmitter release
Give the side effects: Levetiracetam
Irritability
Aphasia
Thrombocytopenia
Toxicity: Sedation
What is the MOA for Ethosuximide?
Blocks T-type calcium channels in thalamus
What is a common cause of temporal lobe epilepsy?
Head trauma
What is the difference in molecular targets between Felbamate and Topiramate?
Felbamate = NMDA antagonist Topiramate = partial AMPA/Kinate antagonist
Difference between side effect and toxicity?
Side effect is a drug effect that is not related to drug’s intended mechanism of action (e.g. developing a rash from taking a sodium channel blocker - Carbamazepine) whereas toxicity is an undesirable effect that is related to the mechanism of action (e.g. sedation, ataxia, diplopia from sodium channel blocking anti-epileptic - Carbamazepine)
What causes carbamazepine toxicity (drunk, dizzy, double vision)?
epoxide metabolite
