Antiepileptic Drugs (Segars) Flashcards
What is Status Epilepticus and what drugs are used in the First and Second IVs to help treat this condition (L/L)?
What are two other drugs that can be used alternatively in the 2nd IV if the first choice drug is NOT available (F/VA)?
SE: seizure persisting for sufficient length of time or is repeated frequently enough that recover between attacks does NOT occur
1st IV: LORAZEPAM (use other Diazepams as alt.)
2nd IV: LEVETIRACETAM (of Fosphenytoin or Valproic Acid)
What 2 states do Na Channel Blockers bind during?
Open State and Fast-Inactivated Gate (Activation Gate is NOT closed during either of these states)
drugs cannot bind to receptors if Activation Gate is closed
What is the probability of Na blockade proportional to and why is it important?
- proportional to FREQUENCY of Na channel opening and dose
- epileptic seizures involve neurons firing at higher frequency than normal –> drugs preferentially act on neurons involved in the disease
What are the 10 Na Channel Blockers we can use for epilepsy?
(C/O/E, L, P, T, VA, L/Z/R)
Which drug ALSO enhances SLOW inactivation of Na Channels?
Cabamazepine (Oxcarbazepine/Eslicarbazepine)
Lamotrigine
Phenytoin (Fosphenytoin - IV use)
Topiramate
Valproic Acid
Lacosamide (Zonisamide/Rufinamide)
Lacosamide enhances slow inactivation too
What two drugs (T/P) inhibit glutamate uptake at the AMPA receptors on the post-synaptic neuron?
Topiramate and perAMPAnel
What drug (F) inhibits glutamate uptake at the NMDA receptors on the post-synaptic neuron?
Felbamate
What seizure does Ethosuximide specifically treat and how?
What is a hallmark finding of this seizure type?
- treats Absence (Petit Mal) seizure by blocking T-Type Ca channels
Hallmark: 3-Hz “spike and wave” activity in the thalamus
What is Zonisamide’s method of action?
- blocks low-threshold Type-T Ca channels on pre-synaptic neurons
What two drugs (L/B) inhibit Synaptic Vesicle 2A (SV2A) proteins?
What is the common suffix of these drugs?
Levetiracetam and Brivaracetam
- suffix: “-acetam”
What two drugs (G/P) block that alpha2delta subunit of T-Type Ca channels on the Presynaptic neuron?
What is similar between these two drugs?
Gabapentin and Pregabalin
- both drugs have “GABA” in them
What drug (E) opens the KCNQ K channel on both the Presynaptic and Postsynaptic neurons?
Ezogabine
What do these drugs target in the Pre-Synaptic GABA neurons:
- Gabapentin and Pregabalin
- Tiagabine
- Vigabatrin
- inc. levels of Glutamic Acid Decarboxylase
- blocks GAT-1 = GABA Transporter 1 (blocks reuptake)
- blocks GABA-T (prevents GABA metabolism)
What three things does Valproic Acid target in the Pre-Synaptic GABA neurons?
- inc. Glutamic Acid Decarboxylase
- blocks GABA-T (prevents GABA metabolism)
- blocks SDD (prevents GABA metabolism)
- Succinic Semialdehyde Dehydrogenase
Post-Synaptic GABA Neuronal Transmission
What is the MOA of Phenobarbitol and Primidone?
MOA: bind to BETA subunit of GABA receptors and increase DURATION of Cl channel opening
- GABA INdependent = INC. TOXICITY
Primidone is a PRODRUG of Phenobarbitol
- both of these drugs are Barbiturates
Post-Synaptic GABA Neuronal Transmission
What is the MOA of Lorazepam, Diazepam, Clonazepam, and Clobazam?
MOA: bind to ALPHA subunit of GABA receptors and cause allosteric change that potentiates GABA binding = Cl channels open with greater frequency
- GABA DEpendent
- all of these drugs are BENZODIAZEPINES
What are the 3 functions of Topiramate?
- inc. frequency of GABA receptor activation
- fast inactivation of Na channels
- AMPA receptor antagonist
What effect do HIGH levels of Ezogabine have on GABA receptors?
- inc. opening of GABA receptors
also used as K Channel opener on Pre- and Post-Synaptic Glutamate neurons
What is the treatment for Dravet Syndrome and Lennox-Gastaut Syndrome?
Cannabidiol
What are the two major risk factors of ALL Anti-Epileptic Drugs?
- Abrupt withdrawal can cause STATUS EPILEPTICUS
2. inc. suicidal behavior and ideations
Phenytoin
What are is pharmacokinetics and what are two serious toxicities it can cause?
P: Zero-order = only so much can be metabolized meaning inc. dosage = TOXIC (serum lvls skyrocket)
T: Gingival Hyperplasia and Hypocalcemia
also well-known CYP450 enzymes
What 4 drugs can cause Osteopenia/Osteoporosis via induction of CYP-450-dependent Vitamin D catabolism?
(C/P/P/VA)
Carbamazepine
Phenytoin
Phenobarbital
Valproic Acid
all dec. circulating Vitamin D lvls = PTH-mediated responses that demineralize bone
Carbamazepine
What enzymes does it induce and what hematological issue can it cause?
- CYP450 enzyme induce that can SELF-METABOLIZE
- can have bone marrow suppressant activity (leukopenia/neutropenia/thrombocytopenia) so make sure to GET BASELINE CBC
Why are Oxcarbazepine and Eslicarbazepine safer options than Carbamazepine?
- both are converted to S-licarbazine which is LESS toxic than the epoxide metabolic product that Carbamazepine produces
What is a major toxicity of Vigabatrin use?
- can cause permanent, progressive, bilateral, concentric VISION LOSS
- D/C after max of 3 months if not reponse
prescribeable ONLY through REMS program
What effect do Valproic Acid and Lamotrigine have on UGT?
- both BLOCK UTG causing accumulation of parent drugs
What effect do Phenytoin, Carbamazepine, and Phenobarbital have on UGT?
- all 3 INDUCE UGT causing reduction or parent drugs
CYP-450 Inducers
What are 3 drugs (C/P/P) can reduce levels of Oral Contraceptives, Warfarin, and Antivirals by inducing clearance via CYP-450?
- Carbamazepine
- Phenytoin
- Phenobarbitol
