Pharmacology of Epilepsy Flashcards
What drugs prolong the fast inactivation state of sodium channels?
- Carbamazepine
- Lamotrigine
- Phenytoin (fosphenytoin)
- Topiramate
- Valproic acid
- Lacosamide
What drug enhance the slows inactivation of sodium channels?
- Lacosamide
What drugs are AMPA receptor blockers?
- Topiramate
- Perampanel
What drug is a NMDA receptor blocker?
- Felbamate
What is the use of ethosuximide?
- Absence seizures –> young child who spaces off in class a lot
What drugs are calcium T-type channel blockers?
- Ethosuximide
- Zonisamide
What drugs are synaptic vesicle 2A protein blockers?
- Levetiracetam
- Brivaracetam
What drugs are alpha-2-gamma calcium channel blockers?
- Gabapentin
- Pregabalin
What drug is a potassium channel opener?
- Ezogabine
What are some drugs that are PRE-synaptic GABA promoting agents?
- Valproic acid
- Gabapentin
- Pregabalin
- Tiagabine
- Vigabatrin
What drugs are GAD stimulators?
- Valproic acid
- Gabapentin
- Pregabalin
What drug is a GAT-1 inhibitor?
- Tiagabine
What drugs are GABA-T inhibitors?
- Vigabatrin
- Valproic acid
Where do benzodiazepines bind to enhance GABA transmission?
- Distinct allosteric site which helps Cl- channels open with greater frequency
Where do barbiturates bind to enhance GABA transmission?
- Distinct site and increases the duration of the Cl- channel opening
What is different about benzodiazepines and barbiturates when enhancing GABA transmission?
- Barbiturates are GABA independent meaning they do not need it
- Benzos are GABA dependent
Why are barbiturates dangerous?
- Because they are GABA independent, there is no limiting factor
What drugs are POST-synaptic GABA promoting agents?
- Benzodiazepines
- Barbiturates
- Topiramate
What is the proposed MOA of cannabidiol?
- Antagonism of GPR55 receptors
- Desensitization of TRPV1 receptors
- Inhibition of adenosine reuptake transport via blockage of ENT-1 receptors
What are some indications of cannabidiol?
- Dravet syndrome
- Lennox-Gastaut syndrome
- Tuberous sclerosis complex
What are some side effects of cannabidiol?
- Hepatocellular injury –> obtain AST/ALT and albumin levels both pre and post therapy
- Sedation/somnolence
What is a broad warning when giving AEDs?
- Abrupt withdrawal may precipitate status epilepticus
- Suicidal behavior and ideation
What is a big side effect of phenytoin, carbamazepine, and phenobarbital?
- Well known inducer of CYP450
What are some select toxicities of phenytion?
- Gingival hyperplasia
- Hypocalcemia/Vit D def/osteoporosis
- Hypothyroidism
What drugs could we see osteopenia/osteoporosis with?
- Carbamazepine
- Phenytoin
- Phenobarbital
- Valproic acid
What are some select toxicities of carbamazepine?
- Hematological –> leukopenia/neutropenia/thrombocytopenia (Need to get a baseline CBC)
- Hypocalcemia/vit D def/osteoporosis
What is special about carbamazepine?
- It induces its own metabolism could make it have less efficacy on seizures
What is oxcarbazepine?
- Analogue of carbamazepine but has fewer CNS/hematological SE’s due to an alternative metabolism
- Less potent CYP450 inducer
What is a big toxicity of vigabatrin?
- Permanent, progressive, bilateral, concentric vision loss
What is needed in order to prescribe vigabatrin?
- Only via REMS program to evaluate risks
What is a big drug-drug interaction with a lot of CYP inducers?
- Oral contraceptive since they make the OCPs less effective –> results in increased unplanned pregnancy
- Anticoagulants –> increase the clearance of warfarin leading to increased risk of thrombosis
- Antivirals –> increased clearance leading to elevated risk of HIV replication
What metabolism do valproic acid and lamotrigine go through?
- NOT CYP450
- Inhibit conjugation of drugs by UGT causing an accumulation of parent drug
What is another metabolism pathway that phenytoin, carbamazepine, and phenobarbital go through?
- Induce conjugation of drugs by UGT causing a reduction of parent drug
What drugs are not cleared by the liver but by the kidney?
- Levetiracetam
- Topiramate
- Oxcarbazepine
- Gabapentin
- Pregabalin
- Vigabatrin
What are some causes of status epilepticus?
- Abrupt withdrawal of AEDs, BZD’s, opioids, alcohol
- Brain mass/tumor
- Infection
- Fever
What is the treatment for status epilepticus?
- IV benzodiazepine
2. Fosphenytoin/valproic acid/levetiracetam/phenytoin
What are the MOAs of topiramate?
- Na+ channel blocker
- AMPA receptor blocker
- Post synaptic GABA promoting agent
What are the MOAs of valproic acid?
- Na+ channel blocker
- GAD stimulation
- GABA-T inhibition
