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ABPN 2022 > AEDs pharmacology > Flashcards

AEDs pharmacology Flashcards

1
Q

Acetazolamide

A

Carbonic anhydrase inhibitor

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2
Q

Carbamazepine MOA

A

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

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3
Q

Clobazam

A

GABA-A receptor agonist

Benzodiazepine derivative (1,5 benzodiazepine with lower abuse potential than 1,4 benzodiazepines like diazepam and lorazepam)

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4
Q

Clonazepam

A

GABA-A receptor agonist

*Benzodiazepines increase channel opening frequency whereas barbiturates increase channel opening duration

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5
Q

Eslicarbazepine

A

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

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6
Q

Ethosuximide

A

Reduces low-threshold T-type Ca currents in thalamic neurons - blocks T-type Ca-channels. *Maybe some action via NaP: persistent sodium current

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7
Q

Ezogabine

A

Potassium channel opener, particularly KCNQ2-5 channels

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8
Q

Felbamate

A

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)

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9
Q

Gabapentin MOA

A

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

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10
Q

Lacosamide MOA

A

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

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11
Q

Lamotrigine MOA

A

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

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12
Q

Levetiracetam MOA

A

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

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13
Q

Oxcarbazepine MOA

A

Metabolite MHD is a blocker of voltage-gated Na channel, slows their recovery: acts on NaF (fast sodium current)

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14
Q

Perampanel

A

Non-competitive antagonist of AMPA receptors on post-synpatic neurons

Can cause severe behavior changes including aggression, anger, homicidal ideation (Fycompa = Fight)

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15
Q

Phenytoin MOA

A

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

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16
Q

Pregabalin MOA

A

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

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17
Q

Rufinamide

A

Reduces the recovery capacity of Na channels, prolonging their inactive state - NaF (fast sodium current)

Treats atonic seizures in LGS (can also use Onfi)

18
Q

Tiagabine

A

Inhibits GABA re-uptake into neurons or glia.

19
Q

Topiramate MOA

A

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

20
Q

Valproate MOA

A

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.

21
Q

Vigabatrin

A

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)

22
Q

Zonisimide

A

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

23
Q

Phenobarbital MOA

A

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

24
Q

Enzyme inducers

A

Phenobarbital (also Primidone)
Phenytoin
Carbamazepine (also Esliscarbazepine, Oxcarbazepine)
Topamax
Zonegran

25
Q

Enzyme inhibitors

A

Depakote

26
Q

Broad spectrum AEDs

A

Valproate - Vicious
Lamotrigine - Lions
and
Topamax - Tigers
Keppra - Kill
Zonisamide - Zebra
(+PHB, Felbamate)

27
Q

Valproate Adverse Effects

A

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

28
Q

Carbamazepine Adverse Effects

A

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

29
Q

Clobazam Adverse Effects

A

Sedation, ataxia, irritability, hyperactivity, psychosis, dry mouth, weight gain, thrombocytopenia

30
Q

Gabapentin/Pregabalin Adverse Effects

A

Can worsen myoclonic or absence seizures, ankle edema, and weight gain

31
Q

Lacosamide Adverse Effects

A

Euphoria at high doses*, cardiac arrhythmias (can trigger atrial fibrillation in patients with known heart disease, prolonged PR interval, AV block)

32
Q

Lamotrigine Adverse Effects

A

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

33
Q

AEDs that can exacerbate myoclonic seizures

A

Carbamazepine

Gabapentin/Pregabalin

Vigabatrin

Lamotrigine

Phenytoin

34
Q

AEDs that can trigger absence status

A

Lamotrigine

Carbamazepine

Phenytoin

35
Q

Keppra Adverse Effects

A

Primarily psychiatric: irritability, depression, psychosis, hostility, impulsivity

36
Q

Phenytoin adverse effects

A

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]

37
Q

Phenobarbital Key Indication/Adverse Effects

A

Drug of choice for neonatal seizrues

Adverse Effects: Fetal depletion of vitamin K, sedation, paradoxical hyperactivity, anemia (2/2 folate depletion), congenital malformation

38
Q

OCP clearance and AEDs

A
39
Q

AEDs and warfarin

A
40
Q

AEDs and anti-virals and immunomodulators

A
41
Q

Valprote effects on AEDs

A

ABPN 2022 (26 decks)

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