Anti-Seizure Flashcards by Chelsea Luedtke

Oldest anti-seizure drug; chronic use is limited by its sedating effects & potential for lethal overdose

Phenobarbital

How well did you know this?

Not at all

Perfectly

Phenobarbital use in seizures (2)

Terminate refractory status epilepticus, neonatal seizures

How well did you know this?

Not at all

Perfectly

Benzodiazepine use in seizures (1)

Used IV to terminate status epilepticus

How well did you know this?

Not at all

Perfectly

Which benzodiazepine, if any, is preferred to treat seizures?

Lorazepam due to its longer duration of action (single dose dependent on re-distribution!!!!)

How well did you know this?

Not at all

Perfectly

BZDs use in seizure treatment long-term

Associated with tolerance, limited usefulness

How well did you know this?

Not at all

Perfectly

T/F: As a group, new anti-seizure agents are slightly more efficacious and better tolerated than traditional agents.

False- equally efficacious

How well did you know this?

Not at all

Perfectly

T/F: Most new anti-seizure agents do not inhibit/induce CYPs and thus have fewer drug interaction

True

How well did you know this?

Not at all

Perfectly

MOA= may increase GABA release, blocks HVA Ca++ channels (—> which may suppress glutamate release)

Gabapentin

How well did you know this?

Not at all

Perfectly

Does gabapentin access the BBB? If so, how?

Yes, L-amino acid transporter

How well did you know this?

Not at all

Perfectly

How is gabapentin excreted?

Unchanged in the urine

How well did you know this?

Not at all

Perfectly

Gabapentin use for seizures (2)
#1: add-on or monotherapy
#2: focal? 
#3: generalized - what types?

Add-on for focal and generalized seizures (doesn’t specify which ones)

How well did you know this?

Not at all

Perfectly

Uses of gabapentin besides being an add-on for focal and generalized seizures include the following EXCEPT:
A. Postherpetic neuralgia & neuropathic pain
B. Migraine
C. Fibromyalgia
D. Binge eating & bulimia
E. Bipolar disorder

D (off-label for topiramate)

How well did you know this?

Not at all

Perfectly

ADEs: mostly well-tolerated

Sedation, dizziness

Gabapentin

How well did you know this?

Not at all

Perfectly

Major MOA of lamotrigine

Blockade of Na+ channels, leading to reduced release of glutamate (from presynaptic neurons)

How well did you know this?

Not at all

Perfectly

MOA= Ca++ channel block, 5-HT3 antagonist

Na+ blockade, leading to reduced release of glutamate

Lamotrigine

How well did you know this?

Not at all

Perfectly

PK: metabolism of lamotrigine
A. Glucuronidation 
B. Excreted unchanged in the urine
C. Not a substrate or inducer for CYPs (mostly devoid of DDIs)
D. Metabolized by 3A4 to active epoxide

A (rate of hepatic clearance is increased by enzyme inducers)

How well did you know this?

Not at all

Perfectly

Uses= Lennox-Gastaut syndrome (multiple refractory seizure types, mental retardation)

Lamotrigine (adjunct is topiramate)

How well did you know this?

Not at all

Perfectly

Lamotrigine use for seizures
#1: add-on or monotherapy
#2: focal/partial?
#3: secondarily generalized - types?
#3: generalized - what types?

Lamotrigine use for seizures
#1: add-on or monotherapy
#2: focal/partial?
#3: secondarily generalized - types?
#3: generalized - what types?

How well did you know this?

Not at all

Perfectly

Alternative to ethosuximide for absence seizures:
A. Gabapentin
B. Lamotrigine
C. Levetiracetam
D. Tiagabine

B (lamotrigine)

How well did you know this?

Not at all

Perfectly

Uses besides those for seizures of lamotrigine

Bipolar disorder maintenance (reduces depressive episodes)

How well did you know this?

Not at all

Perfectly

All AEs: dizziness, ataxia, blurred vision, N/V
Teratogen
Rash/SJS (BBW)

Lamotrigine

How well did you know this?

Not at all

Perfectly

Boxed warning of lamotrigine

Rash/SJS early in therapy

How well did you know this?

Not at all

Perfectly

T/F: A pregnant woman can take lamotrigine for her secondarily generalized tonic-clonic seizures.

False- teratogenic

How well did you know this?

Not at all

Perfectly

MOA: unknown…binds to presynaptic vesicle protein SV2A & may impede impulse conduction

Levetiracetam (no evidence of effects on ion channels or GABA/glutamate)

How well did you know this?

Not at all

Perfectly

T/F: The PK of new anti-seizure agents is less complex, except for levetiracetam.

False- levetiracetam is not bound to plasma proteins and is mostly devoid of DDIs (not a substrate/inducer for CYPs

``` Levetiracetam seizure use: #1: add-on or monotherapy #2: focal/partial? #3: secondarily generalized - types? #3: generalized - what types? (Absence, myoclonic, tonic-clonic, status epilepticus) ```

Add-on, partial or generalized tonic clonic & myoclonic seizures (3 types)

Common ADEs: well-tolerated generally | Fatigue, dizziness, hypertension

Levetiracetam

Serious ADEs of levetiracetam

Behavior symptoms (agitation, hostility, depression, depersonalization)

MOA of tiagabine

Blocks presynaptic and glial GABA reuptake transporter GAT-1 (prolongs inhibitory effect of GABA)

Use= add-on for refractory partial seizures with/without secondary generalization

Tiagabine (blocks GABA reuptake)

Off-label use of this anti-seizure agent is discouraged - may promote seizures in patients without epilepsy

Tiagabine (enhances 3-Hz spike & wave discharges in absence seizures)

Which of the following are correct ADEs of tiagabine? A. Renal calculi, bilateral vision loss B. Tremor, somnolence C. Cognitive impairment (esp. in children), N/V D. Hypertension, dizziness

Which of the following are ADEs of tiagabine? Select all that apply. A. Bilateral vision loss B. Rash/SJS C. Dizziness D. Enhanced 3-Hz spike-and-wave discharges in absence seizure patients

C and D

MOA: Blocks Na+ channels Neuronal membrane hyperpolarization (K+) Enhances postsynaptic GABAa-receptor currents Limits activity of glutamate receptors

Topiramate (Topamax)

MOA includes weakly inhibiting carbonic anhydrase

Topiramate (metabolic acidosis in CNS)

``` Seizure use of topiramate: #1: add-on or monotherapy #2: focal/partial? #3: secondarily generalized - types? #3: generalized - what types? (Absence, myoclonic, tonic-clonic, SE) ```

Monotherapy, partial & generalized tonic-clonic (2!) (*also adjunct for Lennox-Gastaut*)

Adjunct for Lennox-Gastaut syndrome

Topiramate

``` Uses: prophylaxis of migraine A. Tiagabine B. Lamotrigine C. Levetiracetam D. Topiramate ```

Topiramate (Topamax)

``` Which of the following does NOT have migraine listed as a non-seizure use? A. Topiramate B. Levetiracetam C. Valproate D. Gabapentin ```

B (no non-seizure use stated- partial or generalized tonic-clonic & myoclonic)

Which of the following is NOT an off-label use of topiramate (as listed in the handout)? A. Bipolar disorder B. Cluster headaches C. Neuropathy D. Binge eating & bulimia E. Off-label use is discouraged - may promote seizures in patients without epilepsy

A (also weight loss!, E is tiagabine btw)

ADEs: generally well-tolerated Renal calculi Associated with cognitive impairment (an issue esp. when administered to children)

Topiramate (carbonic anhydrase inhibitor; metabolic acidosis in CNS)

MOA vigabatrin

Irreversible inhibitor of GABA transaminase, which blocks GABA degradation (structural analog of GABA)

``` Use of vigabatrin for seizures #1: add-on or monotherapy #2: focal/partial? #3: secondarily generalized - types? #3: generalized - what types? ```

ONLY for refractory complex partial seizures (due to effects on vision, i'm assuming monotherapy?

Non-seizure use of vigabatrin (1)

Monotherapy for infantile spasms (< 2 years old)

Boxed warning for vigabatrin

Progressive and permanent bilateral vision loss

What adverse effect are all anti-seizure medications associated with?

Increased risk of suicidal thoughts or actions

What are the general 1st-3rd therapy options used to reduce seizure occurrence so the patient can live a normal life?

Monotherapy (start dose low and periodically elevate PRN), substitute with another agent (taper off first drug), combination therapy

What AE is associated with long-term therapy with CYP inducing agents?

Reduced fat soluble vitamin levels (ADEK) resulting in osteopenia and bleeding disorders (supplement Vitamin D/Ca and K)

Plasma drug level monitoring is less important for ____ seizures because they occur frequently.

Absence

T/F: Most, but not all, traditional agents increase the risk of fetal malformations.

False- all do!

How would you describe the risk vs. benefit debate of treating epilepsy with potentially teratogenic anti-seizure medications?

The risk of fetal injury from maternal seizures > the risk of drug-induced malformations (using the lowest effective dose!!)

When treating a pregnant epileptic patient, the lowest effective doses should be used. What other action can be taken to reduce the risk of fetal defects?

Folic acid supplements (4 mg daily)

Birth control + traditional agents DDI = ____

Induced CYPs reduce the efficacy of oral contraceptives; BC doses should be increased

How do you terminate a seizure episode of status epilepticus?

IV lorazepam

What do you use for prolonged control of SE after termination?

IV phenytoin (phosphenytoin)

If seizure control is not achieved, what can be used to control SE?

IV phenobarbital (1st lorazepam to terminate, then phenytoin for prolonged control)

4 MOAs of anti-seizure drugs

- Block Na+ channels (voltage-gated, neuronal) - block Ca++ channels (voltage-gated neuronal) - enhance GABA transmission - antagonize glutamate transmission

Which seizure types are mainly inhibited by the blockade of neuronal VG-Na+ channels, which promotes the inactivate state? 1. Focal (partial) 2. Secondarily generalized 3. Generalized 4. Generalized - specifically myoclonic

1 and 2 (focal & secondarily generalized)

T/F: Blockade of voltage-gated neuronal Na+ channels is greater if the membrane is depolarized.

True (voltage-dependent)

Which anti-seizure MOA inhibits absence seizures?

Blockade of thalamic "T type" Ca++ channels (neuronal voltage-gated)

Blockage of pre-synaptic high voltage-activated (HVA) Ca++ channels suppresses excitatory glutamate release. This mainly inhibits ___ seizures. 1. Focal (partial) 2. Secondarily generalized 3. Generalized 4. Generalized - specifically absence

1 (Focal)

T/F: All anti-seizure meds that work by enhancing GABAergic transmission do so by post-synaptic mechanisms.

False- pre or post-synaptic mechanisms

``` What effect does antagonizing neuronal NMDA and/or AMPA receptors have on NT transmission? A. Enhances GABA transmission B. Blocks Ca++ channels C. Antagonizes glutamate D. Enhances glycine transmission ```

C (suppresses glutamate-mediated synaptic excitation)

Phenytoin MOA

Blocks Na+ channels (traditional med)

Formulations= oral (rapid & extended release) and IV (water-soluble phosphate prodrug)

Phenytoin

Non-linear elimination: plasma concentration increases disproportionately as dose is elevated (small increases in dose can result in toxicity)

Phenytoin

Binding % of phenytoin (to albumin)

90%

``` Phenytoin is metabolized by ___ and ____. A. 2C9, 2C19 B. 2D6, 3A4 C. 2C9, 2B6 D. 3A4, 2E1 ```

``` Phenytoin induces CYP___. A. 2E1 B. 2C9 C. 2C19 D. 3A4 ```

D (metabolized by 2c9 and 2c19)

Anti-seizure use of phenytoin includes: 1. Focal (partial) 2. Secondarily generalized 3. Generalized - absence 4. Generalized - specifically myoclonic 5. Generalized - tonic-clonic 6. Generalized - status epilepticus

1, 5, 6 (focal, tonic-clonic, SE)

Used to prevent seizures following neurosurgery

Phenytoin

T/F: Phenytoin is effective against absence seizures.

False

2 DDIs of phenytoin:

Increased BC clearance (induces 3a4, pregnancy) and decreased warfarin clearance (interference 2c9, bleeding)

Boxed warning of phenytoin (IV)

CV events: severe arrhythmias (must be administered slowly, avoid extravasation)

Phentyoin

ADEs: Blood dyscrasias (rare) | Hirsutism in females

Phenytoin

ADEs (all): rare blood dycrasias, gingival hyperplasia, teratogenic, rash, SJS, severe arrhythmias, nystagmus, ataxia, sedation, hirsutism

Phenytoin

Can pregnant women take phenytoin? Why or why not?

No, teratogenic causing fetal hydantoin syndrome (birth defects, mental retardation)

MOA carbamazepine

Blocks Na+ channels (second med traditional)

PK: linear kinetics, more reliable blood levels than SOME OTHER peeps (shady)

Carbamazepine (better than phenytoin's nonlinear PK)

PK: Repeated administration induces its own metabolism + 1A2, 2B6, 2C9, 2C19

Carbemazepine

``` PK: carbamazepine is metabolized by ___ to an active metabolite A. 2c9 B. 3a4 C. 1a2 D. 2c19 ```

B (3A4, active epoxide)

Anti-seizure use of carbemazepine includes: 1. Focal (partial) 2. Secondarily generalized 3. Generalized - absence 4. Generalized - specifically myoclonic 5. Generalized - tonic-clonic 6. Generalized - status epilepticus

1, 5 (focal simple & complex, generalized tonic-clonic)

List 2 other uses of carbamazepine besides tonic clonic & simple/complex focal seizures:

Trigeminal neuralgia, bipolar disorder (mania)

ADEs: CNS= drowsiness, ataxia, vertigo, double vision, blurred vision GI= nausea/vomiting, diarrhea Hyponatremia (SIADH) Teratogenic

Carbamazepine

2 boxed warnings of carbamazepine

Rash/SJS & blood dyscrasias

When giving carbamazepine what screening should be done, if any, and why?

Screen for HLA-B*1502 allele in Asian patients to identify those at risk fo rash/SJS (boxed warning)

Boxed warning= serious aplastic anemia, agranulocytosis; monitor CBC

Carbamazepine

DDIs of carbamazepine (1)

Warfarin

Which of the following does NOT describe the MOA of valproic acid (Depakote, divalproex)? A. Blocks Na+ channels B. Blocks HVA Ca++ channels C. Blocks T-type Ca++ channels D. Stimulates GABA synthesis & inhibits its degradation

B (GABA effects: stimulates glutamate decarboxylase & inhibits GABA transaminase)

Use of valproic acid (Depakote, divalproex) in seizures 1. Focal (partial) 2. Secondarily generalized 3. Generalized - absence 4. Generalized - specifically myoclonic 5. Generalized - tonic-clonic 6. Generalized - status epilepticus

1, 3, 4, 5 ("broad spectrum")

Which of the following are 2 uses of valproic acid (besides for seizures)? A. Migraine prophylaxis, trigeminal neuralgia B. Neuropathic pain, bipolar disorder C. Bipolar disorder, migraine prophylaxis D. Lennox-Gastaut syndrome, cluster headaches

C (bipolar mania & migraine prevention)

What is the formulation of divalproex?

1:1 acid/salt of valproic acid

ADEs (all listed but possible black box warnings): CNS= sedation, ataxia, tremor, weight gain GI= anorexia, nausea, vomiting

Valproic acid (Depakote, divalproex - minimized ADEs with enteric coating)

Can a pregnant women take divalproex? Why or why not?

No, teratogenic (valproic acid)

2 boxed warnings of valproic acid

Hepatic toxicity/pancreatitis and teratogenic

Boxed warning for hepatic toxicity and pancreatitis esp. in children < 2 years and fairly soon after therapy is started; monitor ALT/AST

Valproic acid (Depakote, divalproex)

Boxed warning for teratogenicity: neural tube defects & decreased IQ, may DC during pregnancy or give high dose folic acid

Valproic acid (Depakote, divalproex)

Ethosuximide MOA

Blocks T-type Ca++ channels (in thalamic neurons)

Ethosuximide use: 1. Focal (partial) 2. Secondarily generalized 3. Generalized - absence 4. Generalized - specifically myoclonic 5. Generalized - tonic-clonic 6. Generalized - status epilepticus

3 (drug of choice for uncomplicated absence seizures)

ADEs: generally well tolerated CNS= drowsiness, lethargy, dizziness, headache, hiccup GI= nausea, vomiting, anorexia

Ethosuximide

``` Which of the following is NOT a rare ADE of ethosuximide, which is generally well-tolerated (GI/drowsiness/headache)? A. Hepatic toxicity & pancreatitis B. Lupus C. Aplastic anemia D. SJS ```

A (ALSO *leucopenia*, hepatic toxicity/pancreatitis is a boxed warning for valproic acid)

Anti-Seizure Flashcards

(102 cards)