AEDs pharmacology Flashcards
Acetazolamide
Carbonic anhydrase inhibitor
Carbamazepine MOA
Prevents repetitive firing of voltage-gated Na-channels, slows recovery of Na-channels: NaF (fast sodium current)
Also works on Ca L-type channels
Auto-inducer
Clobazam
GABA-A receptor agonist
Benzodiazepine derivative (1,5 benzodiazepine with lower abuse potential than 1,4 benzodiazepines like diazepam and lorazepam)
Clonazepam
GABA-A receptor agonist
*Benzodiazepines increase channel opening frequency whereas barbiturates increase channel opening duration
Eslicarbazepine
Similar to CBZ, i.e., inhibition of voltage-gated Na channels through slower channel recovery: NaF (fast sodium current)
Has longer half-life compared to CBZ
Ethosuximide
Reduces low-threshold T-type Ca currents in thalamic neurons - blocks T-type Ca-channels. *Maybe some action via NaP: persistent sodium current
Ezogabine
Potassium channel opener, particularly KCNQ2-5 channels
Felbamate
Inhibition of NMDA receptors
Potentiation of GABA-A receptors
Can cause rare but fatal aplastic anemia or hepatotoxicity (I FELL down because Felbatol made me so sick)
Gabapentin MOA
Bind pre-synaptic voltage-gated Ca channels (HVA, alpha-2-delta-1 subunit), resulting in inhibition of excitatory neurotransmitters
Also enhances GABA turnover
Structurally similar to GABA but does NOT bind GABA receptor
Excreted unchanged in urine
Lacosamide MOA
Enhances slow inactivation of voltage gated Na channels (NaP: persistent sodium current), resulting in stabilization of neuronal membranes
Binds to collapsing response mediator protein 2 (CRMP-2), which is associated with neuronal outgrowth
Excreted without metabolism
Lamotrigine MOA
Inhibition of voltage-gated Na channels: slows their recovery - NaF (fast sodium current)
Inhibits high-voltage calcium currents (mediated by multiple channel types) - HVA calcium channel
Metabolism: hepatic glucuronidation
Depakote: decreases hepatic glucuronidation and increases lamotrigine levels
Pregnancy / hormonal interactions: 1.) Metabolism increased by estrogen-based OCPs 2.) Metabolism increased during pregnancy (monitor levels during & after, related to estrogen levels) and taper after childbirth
Levetiracetam MOA
Acts on the synaptic vesicle protein 2A (SV2A).
Inhibits N-type Ca currents: HVA
Also acts on GABA: Rev DMCM
Renal excretion without involvement of CP450 system
*Brivaracetam: inhibits SV2A protein with 30% greater affinity; not as many mood side effects as Keppra
Oxcarbazepine MOA
Metabolite MHD is a blocker of voltage-gated Na channel, slows their recovery: acts on NaF (fast sodium current)
Perampanel
Non-competitive antagonist of AMPA receptors on post-synpatic neurons
Can cause severe behavior changes including aggression, anger, homicidal ideation (Fycompa = Fight)
Phenytoin MOA
Blockage of voltage-gated Na channels: NaF (fast sodium current) and NaP (persistent sodium current)
Zero-order kinetics, unpredictable levels at high doses
Enzyme inducer
Pregabalin MOA
Bind pre-synaptic voltage-gated Ca channels (alpha-2-delta-1 subunit), resulting in inhibition of excitatory neurotransmitters
Also enhances GABA turnover
Excreted unchanged in urine
Rufinamide
Reduces the recovery capacity of Na channels, prolonging their inactive state - NaF (fast sodium current)
Treats atonic seizures in LGS (can also use Onfi)
Tiagabine
Inhibits GABA re-uptake into neurons or glia.
Topiramate MOA
Carbonic anhydrase inhibition
Blockage of voltage-gated Na channels: NaF (fast sodium current), NaP (persistent sodium current)
Increase in GABA-A receptor activity
AMPA/kaynate antagonist
Also works on Ca+ channel block: HVA
Enzyme inducer
Renally excreted
Valproate MOA
1.) Inhibition of voltage-gated Na channels. : NaF (fast sodium current) and NaP (slow sodium current) 2.) Activation of K conductance. 3.) Increases GABA by inhibition of GABA-transaminase (GABA-T). 4.) Reduces Ca L-type channel current. 5.) Possibly reduces low threshold (T-type) Ca channel current.
Vigabatrin
AKA Sabril
Inhibition of GABA-T, preventing the breakdown of GABA, increasing its concentration
For infantile spasms in TS patients
Can cause irreversible peripheral vision loss (30%) (Sabril = Sight)
Zonisimide
Carbonic anhydrase inhibition
Blocks repetitive firing of voltage-gated Na channels: NaF (fast sodium current)
Reduces T-type calcium current without affecting L-type current
Similar MOA to Topamax, but longer half-life
Enzyme-inducer
Renally excreted
Phenobarbital MOA
Main mechanism is post-synaptic binding of GABA-A receptors (prolongs opening time, increasing Cl influx).
Long half life (>72 hours in adults, 110 hours in children)
Enzyme inducer
Primidone: metabolized into Phenobarbital (PHB) & Phenylethylmalonamide (PEMA)
*Also acts on HVA Ca-channel block and AMPA glutamate receptor
Enzyme inducers
Phenobarbital (also Primidone)
Phenytoin
Carbamazepine (also Esliscarbazepine, Oxcarbazepine)
Topamax
Zonegran
Enzyme inhibitors
Depakote
Broad spectrum AEDs
Valproate - Vicious
Lamotrigine - Lions
and
Topamax - Tigers
Keppra - Kill
Zonisamide - Zebra
(+PHB, Felbamate)
Valproate Adverse Effects
General: Hepatotoxicity, hyperammonemia, weight gain, thrombocytopenia, male pattern balding, acute pancreatitis
Pregnancy: Neural tube defects, lower IQ, other anomalies, autism
Increases LTG blood levels by inhibiting hepatic glucuronidation à increased risk of SJS
Carbamazepine Adverse Effects
SJS (highest with Carbamazepine): Increased risk w/HLA-B*1502 allele in Han Chinese, FDA recommends genotyping all Asian patients prior to initiating treatment
Hyponatremia – WORSE WITH OXC
Clobazam Adverse Effects
Sedation, ataxia, irritability, hyperactivity, psychosis, dry mouth, weight gain, thrombocytopenia
Gabapentin/Pregabalin Adverse Effects
Can worsen myoclonic or absence seizures, ankle edema, and weight gain
Lacosamide Adverse Effects
Euphoria at high doses*, cardiac arrhythmias (can trigger atrial fibrillation in patients with known heart disease, prolonged PR interval, AV block)
Lamotrigine Adverse Effects
Rash (10-12%), SJS (BLACK BOX WARNING!): Increased risk with rapid titration, high initial dose, concomitant VPA therapy
Not an inducer of Vit D metabolism
May exacerbate myoclonic seizures
Lamotrigine can trigger absence status epilepticus as well as Carbamazepine and Phenytoin
AEDs that can exacerbate myoclonic seizures
Carbamazepine
Gabapentin/Pregabalin
Vigabatrin
Lamotrigine
Phenytoin
AEDs that can trigger absence status
Lamotrigine
Carbamazepine
Phenytoin
Keppra Adverse Effects
Primarily psychiatric: irritability, depression, psychosis, hostility, impulsivity
Phenytoin adverse effects
Long term use: cerebellar atrophy, gingival hyperplasia, osteoporosis, hirsutism, aplastic anemia, many more
IV infusion: cardiac arrhythmias, hypotension, purple glove syndrome (pain, discoloration, edema)
Fosphenytoin (phosphorylated phenytoin [lacks propylene glycol]): can load (IV or IM) w/ less risk of adverse effects [thus there are fewer cardiac side-effects]
Phenobarbital Key Indication/Adverse Effects
Drug of choice for neonatal seizrues
Adverse Effects: Fetal depletion of vitamin K, sedation, paradoxical hyperactivity, anemia (2/2 folate depletion), congenital malformation
OCP clearance and AEDs
AEDs and warfarin
AEDs and anti-virals and immunomodulators
Valprote effects on AEDs
