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Clinical 2 (Part B) > 13 - Seizure Disorders > Flashcards

13 - Seizure Disorders Flashcards

1
Q

Define a seizure

A
  • occurs due to abnormal excessive and/or synchronous neuronal activity in the brain
  • abnormal, paroxysmal, excessive firing of CNS neurons - transient event (doesn’t last)
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2
Q

Define epilepsy

A

chronic condition characterized by recurrent seizures which are not provoked by systemic or acute neurologic insults - enduring predisposition for seizures

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3
Q

Define status epilepticus

A

seizure lasting > 30 minutes or >2 sequential seizures without return to normal mental baseline

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4
Q

What is the diagnostic criteria for epilepsy?

A

Epilepsy is defined as when any of the following exist:

  • At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart.
  • One unprovoked or reflex seizure and a probability of further seizures similar to the general recurrence risk after 2 unprovoked seizures occurring over the next 10 years. This may be the case with remote structural lesions such as stroke or certain types of traumatic brain injury.
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5
Q

How can we treat epilepsy ?

A

Antiepileptic drugs, diet, surgery/VNS

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6
Q

60% of new patients with epilepsy are ______ or ______

A

young or elderly

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7
Q

What is the first step when a patient presents with their first seizure?

A

Need to rule out other physiologic (and possibly treatable) causes before beginning therapy for seizure disorder or epilepsy

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8
Q

What are the two branches of seizure types? Describe them.

A

1) Focal - small area of brain or can involve up to 1 whole hemisphere
2) Generalized - both hemispheres involved

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9
Q

What are types of generalized seizures? Describe them

A

Absence: “spaced out”

Tonic: Stiff or flexed (fall backward)

Clonic: Convulsions

Atonic: Relaxed (fall forward)

Myoclonic: Short muscle twitches

Tonic-clonic: Tonic and clonic phase (Stiff and convulsions)

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10
Q

_______ = GABA; binds to post -synaptic GABAa receptor to open Cl- ion channels and allow influx (makes it less likely to fire)

A

inhibitory

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11
Q

_______ = Glu binds to glutamate receptor (NMDA or non-NMDA type); net result is excitatory postsynaptic potential (makes it ready to fire)

A

excitatory

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12
Q

In seizure disorders, there is more _______ and less _______

A

more excitation and less inhibition

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13
Q

Goals of therapy for seizures

A

1) Eliminate seizures (reduce seizure frequency and severity)
2) Minimize SE

3) Optimize quality of life
- Address comorbid anxiety, depression
- Driving, economic security, relationships/family planning, safety, social isolation, stigma

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14
Q

General Principles for Treatment:

-Verify ______ of epilepsy and determine ______ if possible

A

Verify diagnosis of epilepsy and determine ethology if possible

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15
Q

General Principles for Treatment:

Match choice of AED to ____ ____

A

seizure type

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16
Q

General Principles for Treatment:

Use _____ if possible, _________ if necessary.

A

Use monotherapy if possible, polytherapy if necessary

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17
Q

General Principles for Treatment:

Consider changing the _____ of dosing to reduce toxicity

A

timing

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18
Q

When is treatment indicated?

A

Generally, once a patient meets the criteria for diagnosis of epilepsy (either > 2 unprovoked seizures > 24 hours apart or one seizure with risk factors that increase risk of recurrence), treatment is indicated!

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19
Q

Focal Seizure Type:

What 3 drugs are in both guidelines?

A
  • Carbamazepine
  • Levetiracetam
  • VPA
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20
Q

Generalized tonic-clonic (adult) Type:

What 4 drugs are in both guidelines?

A
  • Carbamazepine
  • Lamotrigine
  • VPA
  • Oxcarbazepine
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21
Q

Absence (children):

What 2 drugs are in both guidelines?

A
  • Ethosuximide

- VPA

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22
Q

What are common side effects for all AEDs (anti-epileptic drugs) ?

A

CNS:

  • drowsiness, sedation, fatigue
  • incoordination
  • dizziness
  • cognitive impairment (mental dulling, memory, concentration)
  • diplopia (double vision)

GI side effects

Toxicities are additive (i.e. worsen with each additional AED added)

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23
Q

Are dose-related side effects reversible?

A

yes - upon lowering or d/c AED

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24
Q

What are some neurologic dose related SE’s ?

A

Neurologic:

  • drowsiness, sedation
  • impaired cognition
  • mood changes
  • irritability hyperactivity
  • insomnia
  • dizziness, vertigo
  • ataxia
  • headache
  • sensory neuropathy
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25
Q

What are some systemic dose related SE’s?

A

Systemic:

  • GI
  • Benign elevation of liver enzymes
  • Benign leukopenia
  • Gingival hyperplasia
  • Weight gain
  • Anorexia
  • Hair loss
  • Hirsutism
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26
Q

Describe idiosyncratic reactions

A
  • More serious and potentially life threatening
  • Not dose-related
  • No lab test/level identifies risk for idiosyncratic reaction
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27
Q

What are some risk factors for idiosyncratic reactions?

A

Hx of previous drug reactions, liver/kidney function, conditions affecting hematopoiesis, metabolic disorders

28
Q

HLA-B* 1502 gene can cause ??

A

carbamazepine-induced SJS

29
Q

What are the 2 MOA of idiosyncratic reactions?

A

1) Immune-mediated reaction to the drug

2) Genetics - unusual sensitivity to the drug

30
Q

What are hypersensitivity reactions? And give examples

A
  • Stevens-Johnson syndrome (SJS)
  • Toxic Epidermal Necrosis (TEN)
  • Drug rash with eosinophilia and systemic symptoms (DRESS)

Characterized by fever & rash

31
Q

List some other idiosyncratic reactions?

A
  • Agranulocytosis
  • Aplastic anemia
  • Thrombocytopenia
  • Hepatotoxicity
  • Pancreatitis
  • Connective tissue disorder
32
Q

What do we NEVER EVER EVER give to women of childbearing age? Why?

A

Valproic acid!!

  • Greater risk of malformation and possible neurodevelopment impairment with VPA
  • Avoid in pregnancy and in women of childbearing age
33
Q

What 2 things cause greater risk of malformation and possible neurodevelopment impairment ?

A

1) Valproic acid

2) Polytherapy (particularly with VPA)

34
Q

All females on AED should receive _____ _____ before any possibility of pregnancy

A

folic acid

35
Q

Give examples of CYP P450 inducers

A

carbamazepine, phenytoin, phenobarbital

36
Q

Give examples of CYP P450 inhibitors

A

valproate

37
Q

When should serum level monitoring be done?

A

Only be done if clinically indicated:

  • To assess non-adherence
  • Suspected toxicity
  • Adjustment of phenytoin dose
  • Management of PK interactions (ex. change in bioavailability, elimination, co-medication with interacting drugs)
  • Special clinical conditions: status epilepticus, organ failure, pregnant while on LMT or PHT (levels affected by pregnancy)
38
Q

______ follows michaelis mention kinetics

A

phenytoin

39
Q

How can we manage adverse effects?

A

1) Dose escalation rate
2) Habituation period (time to allow adverse effects to occur - varies between patients)
3) Blood levels (rate of increase, peaks)
4) Timing of doses (single vs spread our vs ER formulation)
5) PK interactions (drug interactions - change in metabolism)
6) PD interactions (additive or synergistic adverse effects)

40
Q

SE management:

For new AEDs, test dose at _____

A

bedtime

  • if side effects, delay next dose
  • if side effects recur, reduce dose
  • increase dose as tolerated
41
Q

SE management:

Administer with food to ____ the rate of absorption

A

slow

42
Q

When should a patient expect to see results in seizure frequency and severity?

A

Improvement: 1-2 weeks
Significant benefit: 1 month
*after at max dose

43
Q

How are we titrating AED’s?

A

for most every 1-2 weeks

44
Q

When should a pharmacist follow up with a patient after starting AED?

A

at 1 week and then every 3 days for dose changes

45
Q

What needs to be tested and when?

A

CBC, LFT, electrolytes

@ Baseline and q3-6 months initially

46
Q

When can someone d/c seizure meds? How should it be done?

A

Up to the patient when they have had a seizure-free period of > 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes

Favorable factors:

  • Control achieved easily on one drug at low dose
  • No previous unsuccessful attempts at withdrawal
  • Normal neurologic exam at EEG

Consider relative risk/benefit

  • To be done SLOWLY
  • At least 2-3 months (up to 6+ months for benzos and barbiturates)
  • One drug at a time
47
Q

Why is status epilepticus a neurologic emergency ?

A
  • Associated with brain damage, tx resistance, and death

- Poorer outcomes increase with increased seizure duration

48
Q

When is immediate care of status epileptics required?

A

1) Seizure lasting > 5 minutes

2) Repeated convulsive seizures (>3 in one hour)

49
Q

What is supportive treatment for status epilepticus ?

A
  • patient stabilization
  • adequate oxygenation
  • preservation of cardiorespiratory function
  • management of systemic complications
  • aggressive assessment of underlying causes
50
Q

What are abortive treatments for status epilepticus ? ABORTION FOR SEIZURES NOT BABIES

A

1) Benzo (lorazepam, diazepam) - buccal midazolam if IV not available
- 1st line for active seizures including status epilepticus
- Effective in terminating seizures in 75-90% of patients

2) Anticonvulsant (phenobarb, phenytoin)
- 2nd line if benzodiazepine does not terminate seizure

51
Q

A ______ diet may be beneficial

A

ketogenic

52
Q

What antiepileptic drugs help with the following patient characteristic:

Depression

A

Lamotrigine, oxcarbazepine

mood stabilizing effects

53
Q

What antiepileptic drugs help with the following patient characteristic:

Migraine

A

Topiramate, valproate

54
Q

What antiepileptic drugs help with the following patient characteristics:

Chronic pain

A

Pregabalin, gabapentin, oxcarbazepine, carbamazepine, lacosamide

(specifically, neuropathic pain)

55
Q

What antiepileptic drugs help with the following patient characteristics:

Obesity

A

Topiramate, zonisamide

56
Q

What antiepileptic drugs help with the following patient characteristics:

Women of childbearing potential

A

avoid VPA

57
Q

What antiepileptic drugs help with the following patient characteristics:

Older adults

A

Lamotrigine, gabapentin, topiramate

58
Q

What antiepileptic drugs help with the following patient characteristics:

Asian

A

Avoid carbamazepine (HLA-B 1502 allele = risk of hypersensitivity reactions)

59
Q

What antiepileptic drugs help with the following patient characteristics:

Nephrolithiasis

A

Avoid topiramate and zonisamide

If benefit > risk, suggest increased water intake

60
Q

What antiepileptic drugs help with the following patient characteristics:

Atopic (rash prone)

A

Avoid Lamotrigine and carbamazepine

61
Q

Which drugs decrease concentration of birth control ?

A
  • phenobarb
  • phenytoin
  • carbamazepine
  • topiramate
  • oxcarbazepine
62
Q

What drug does estrogen decrease the concentration of ?

A

lamotrigdine

63
Q

What are some important lifestyle things that you want to know about a patient who has seizures ?

A
  • do they drive?
  • alcohol
  • recreational drug use
  • sleep habits
  • caffeine
  • insurance ?
64
Q

How do we manage AED and OCP interactions?

A
  • Ideally, select an alternative, non-interacting agent or alternative contraceptive method (ex. Depo Provera, Mirena)
  • If possible, use OCP continuously (no placebo break) = continuous suppression of gonadotropin secretion and ovarian function
  • Use OCP with progestin component high enough to suppress ovulation (as estrogen is the hormone most effected by AED use)
  • Or use “high dose” estrogens (> 50 mpg)
65
Q

What are some potential seizure triggers?

A
  • missed medication
  • stress/anxiety
  • missed sleep
  • hormonal changes
  • acute illness
  • alcohol/drug use
  • drug interactions
  • overexertion
  • poor diet/missed meals
66
Q

For the exam:

Know the TABLE (for each categories pick 2-3 drugs and know them really well)

A

okay man

Clinical 2 (Part B) (30 decks)

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