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Seizures- Pharm > Seizures > Flashcards

Seizures Flashcards

1
Q

What is a seizure

A

Paroxysmal event caused by excessive electrical discharge of neurons
May disturb consciousness, sensory or motor systems
Discharges seen as spikes on EEG

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2
Q

What is epilepsy?

A

Group of chronic neurological disorders characterized by unprovoked recurrent seizures, usually idiopathic

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3
Q

What is status epilepticus

A

Prolonged seizures without recovery in between

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4
Q

Absent Seizure (loss of consciousness)

A

Sudden onset
Blank stare, upward rotation of eyes
Typically in young children
Consciousness returns instantly

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5
Q

Generalized clonic tonic seizures

A 
Muscle rigidity (tonic) followed by sharp contractions (clonic)
Crying/moaning, tongue biting, incontinence
Confusion upon return to consciousness
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6
Q

Myoclonic

A

Brief sudden muscle contractions

Face, trunk, extremities

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7
Q

Atonic

A

Complete loss of muscle tone

Drop attacks

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8
Q

Tonic and Clonic

A

Tonic
Uncontrolled extension of muscle groups

Clonic
Repeated rhythmic jerking of arms and legs

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9
Q

Simple Partial Seizures

A

without loss of consciousness
Motor symptoms
Somatosensory symptoms (aura for GTC
Psychic symptoms (automatisms)

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10
Q

Complex partial seizures

A

with loss of consciousness
Memory loss, abnormal behaviors
May progress to GTC

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11
Q

Secondarily generalized seizures

A

with loss of consciousness

Begins as partial

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12
Q

Epidemiology of Seizures

A

Approximately 8% of the general population will have at least one seizure in a lifetime
Recurrence within 5 years of a first unprovoked seizure  23% - 80%

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13
Q

Epidemiology of epilepsy

A

Incidence = 44 per 100,000 person-years
Bimodal distribution
One peak during the first year of life
One peak after age 65

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14
Q

After first seizure, the risk of having a second seizure within 8 years?

A

33%

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15
Q

Of those who did have a second seizure, risk of third seizure?

A

73%

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16
Q

Of those who did not have second seizure within 8 years?

A

Seizure-free for life

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17
Q

Etiology of Seizures

A

70% idiopathic

30% have secondary causes
Medication-induced (prescription or illicit)
Alcohol
Electrolyte abnormalities
Trauma
Stroke
Tumors, cancer
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18
Q

Goals of therapy for seizures (2)

A

Decrease seizure activity, ideally want patient to be seizure free!

Improve quality of life
If complete seizure control is not experienced, QOL suffers
Other conditions are likely present

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19
Q

Phenytoin (Dilantin®) Indicated for (2)

A

Primary generalized

Partial seizures

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20
Q

Phenytoin (Dilantin®) Advantages (2)

A 
Well studied (has been used for 65 years)
Many dosage forms
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21
Q

Phenytoin (Dilantin®) Disadvantages (4)

A

Kinetics – challenging to determine dosing
narrow therapeutic window
Drug interactions (CYP inducer, highly protein bound)
Close monitoring is required
Extensive side effect profile

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22
Q

What involves the phenytoin sodium?

A

capsules

injectable preparations

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23
Q

What involves the phenytoin acid?

A

chewable tablets

suspension

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24
Q

Phenytoin Dosing is calculated how?

A 
loading dose= (Vd) (Css desired)/ (s)(F)
Vd = Volume of distribution (with normal albumin)
0.65L/kg
S = Fraction of active drug in salt form
0.92 (phenytoin sodium)
1.0 (phenytoin acid)
F = bioavailability
Css= concentration at steady state
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25
Q

What 3 things need to be monitored for Phenytoin?

A

CBC
LFTs
Albumin

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26
Q

2 Risks with taking phenytoin?

A

Risk of suicidal ideation

Pregnancy Category D

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27
Q

What serum monitoring due to a therapeutic index for phenytoin

A

10-20 mcg/mL (total)

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28
Q

What are some adverse affects of Phenytoin?

A 
Nausea, vomiting, diarrhea  take with meals to  GI upset
Dizziness, diplopia
Insomnia, fatigue, irritability
Headache
Gingival hyperplasia
Hirsutism
Mild peripheral neuropathy
Coarsening of facial features
Abnormalities of vitamin D metabolism  osteomalacia
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29
Q

What are 3 dose related adverse effects for phenytoin?

A

20 mcg/ml: Nystagmus
30 mcg/ml: Ataxia, diplopia, slurred speech
>40 mcg/ml: Sedation, lethargy, tremor

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30
Q

Drugs that increase phenytoin levels?

A

acute alcohol intake, salicylates, estrogens, H2-antagonists

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31
Q

Drugs that decrease phenytoin levels?

A

carbamazepine, chronic alcohol abuse, antacids with calcium, phenobarbital, rifampin

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32
Q

Phenytoin and Warfarin–> protein binding

A

an immediate reaction

Phenytoin can displace warfarin which may result in a rapid INCREASE in INR

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33
Q

Phenytoin and Warfarin–>CYP 2C9 induction

A

after prolonged administration

Phenytoin induces the metabolism of warfarin which may result in a DECREASE in INR

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34
Q

Phenytoin and Warfarin–> Depletion of Vitamin-K dependent clotting factors

A

Warfarin inhibits the synthesis of clotting factors
Phenytoin may also deplete these clotting factors
May result in a further INCREASE in INR

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35
Q

Carbamazepine – CBZ Advantages and Disadvantages

A

Advantages
Well studied

Disadvantages
Active metabolite
Auto-inducer, drug interactions**
CNS side effects**

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36
Q

Carbamazepine – CBZ is indicated for?

A 
Primary generalized (in a non-emergent situation)
Partial seizures (newly diagnosed)
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37
Q

Carbamazepine– 3 things to monitor

A

Serum monitoring is not required but can be used to determine toxicity
4-14mcg/mL

WBC, ANC monitoring
Idiopathic blood dyscrasias
Mild persistent leukopenia

Drug interactions
CYP inhibitors

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38
Q

Carbamazepine have 5 ADR’s

A 
Diplopia
Dizziness, unsteadiness
Drowsiness, lethargy
Nausea, GI upset
Rash
39
Q

Carbamazepine is contraindicated with?

A

Hypersensitivity to TCAs

Bone marrow suppression

40
Q

Carbamazepine Black Box Warning

A

Blood dyscrasias

Patients of Asian descent should be screened for HLA-B*1502 allele prior to initiating therapy

41
Q

Oxcarbazepine (Trileptal®) Advantages and Disadvantages

A

Advantages
Comparable efficacy to phenytoin, valproic acid, and CBZ, but may be better tolerated

Disadvantages
Hyponatremia
Drug interactions

42
Q

Oxcarbazepine (Trileptal®) indicated for?

A

Partial seizures (monotherapy or adjunctively)
GTC seizures
Pregnancy Category C

43
Q

Oxcarbazepine (Trileptal®) CNS related ADR’s

A

Cognitive symptoms, including difficulty with concentration, psychomotor slowing, and speech or language problems
Somnolence or fatigue
Coordination abnormalities, including ataxia and gait disturbances

44
Q

Topiramate (Topamax®) Advantages and Disadvantages

A

Advantages
Few drug interactions
Weight loss?

Disadvantages
Cognitive functioning impairment
Kidney stones
Weight loss?

45
Q

Topiramate (Topamax®) common ADR’s

A

Cognitive impairment - Poor concentration, confusion, word-finding difficulties
Ataxia, dizziness
Somnolence
Weight loss

46
Q

Topiramate (Topamax®) Drug interactions

A 
OCs may be less effective- higher estrogen doses may be required
Digoxin - ↓ concentration
Valproic acid - ↑ risk of hyperammonemia
Phenytoin, CBZ, barbiturates
CNS depressants
47
Q

Lamotrigine (Lamictal®) Advantages and Disadvantages

A

Advantages
Not highly protein bound
Does not cause weight gain

Disadvantages
Rash
Drug interactions

48
Q

Lamotrigine (Lamictal®) alternative for what type of seizures?

A

absent seizures

49
Q

Lamotrigine (Lamictal®) ADR

A 
Coordination abnormalities
Anxiety, mania
Diplopia
Insomnia
Drowsiness, fatigue
hypersensitivity--> may cause SJS
50
Q

Agents that cause visual abnormalities (6)

A

Lacosamide

Lamotrigine

Phenytoin

Pregabalin

Tiagabine

Vigabatrin

51
Q

4 anticonvulsants that cause weight loss

A

Ethosuximide
Felbamate
Topiramate
Zonisamde

52
Q

4 anticonvulsants that cause weight gain

A

Gabapentin
Pregabalin
Valproic Acid
Vigabatrin

53
Q

Valproic Acid advantages and disadvantages?

A

Advantages
Well studied
Multiple dosage forms

Disadvantages
Side effect profile
Drug interactions
Enzyme inhibitor

54
Q

Valproic Acid serum monitoring

A

Serum monitoring not typically required but can be used to determine toxicity and dosage adjustments
50-150 mcg/mL

55
Q

Valproic Acid common ADR’s

A 
Nausea, vomiting, abdominal pain, heartburn
Sedation
Fine hand tremor
Weight gain and increased appetite
Hair loss
Hepatotoxicity
Thrombocytopenia
pregnancy cat D
56
Q

Gabapentin – Neurontin®

A

Advantages
No known drug interactions

Disadvantages
Very high doses required for seizure control
Increased dosing frequency

57
Q

Gabapentin – Neurontin® Pharmacokinetics

A

Not metabolized (renally excreted unchanged)
Does not induce hepatic enzymes
Half-life: 5-8 hours

58
Q

Gabapentin – Neurontin® ADR

A 
Somnolence
Ataxia
Tremor
Dizziness
Headache
Pregnancy Cat C
59
Q

Levetiracetam – Keppra® Advantages and Disadvantages

A

Advantages
No known drug interactions
Various dosage forms
Pediatric use

Disadvantages
Limited indications

60
Q

Levetiracetam – Keppra® Common ADR’s

A

Somnolence, asthenia, dizziness, vertigo, headaches

Not dependent on dose or dose titration

61
Q

Pregabalin – Lyrica® Advantages and Disadvantages

A

Advantages
No known drug interactions

Disadvantages
Brand name only, expensive
Schedule V

62
Q

Pregabalin – Lyrica® Common ADR

A 
Dizziness, ataxia
Somnolence
Peripheral edema, Weight gain
Headache
pregnancy Cat C
63
Q

Tiagabine – Gabitril®

A 
adjunct therapy
Half-life = 6.7 hours
Extensively metabolized by CYP3A4
highly protein bound
Titration is extremely slow***
64
Q

Tiagabine – Gabitril® ADR

A 
Dizziness
Fatigue
Generalized muscle weakness
Nervousness
Tremor
Abnormal thinking
Depression
Aphasia
Encephalopathy
prey cat C
65
Q

Zonisamide – Zonegran® ADR

A

Fatigue, dizziness, ataxia, somnolence, anorexia/weight loss, psychomotor slowing

Pregnancy Category C

66
Q

Phenobarbital – Luminal® Advantages and Disadvantages

A

Indicated for:
All seizure disorders!

Advantages
Oldest anti-epileptic drug
Broad-spectrum

Disadvantages
Pan-inducer
Toxicity

67
Q

Phenobarbital – Luminal® Therapeutic levels

A

Therapeutic levels
15-40 mcg/ml
adjust for renal and hepatic dysfunction

68
Q

Phenobarbital – Luminal® ADR

A

Dependence
CNS depression
pret cat D

69
Q

Phenobarbital- Luminal withdrawal symptoms

A

convulsions and delirium

70
Q

Primidone – Mysoline® (5)

A

Converted to phenobarbital via hepatic oxidation

Therapeutic levels of primidone: 8-12 mcg/ml

Half-life of primidone: 6-8 hrs

Pregnancy category D

Adverse effect profile similar to phenobarbital

71
Q

Ethosuximide – Zarontin® indicated for?

A

FDA approved for absence seizures**
First line for absent seizures**
BID

72
Q

Ethosuximide – Zarontin®
Dose related adverse effects
Drug interactions

A

Not protein bound

Drug interactions
Clearance ’d by valproic

Common dose-related adverse effects
Gastric distress
Fatigue
Headache
Dizziness
Hiccups
Euphoria
73
Q

Felbamate – Felbatol® indicated for?

A

Effective for partial seizures

Causes aplastic anemia and severe hepatitis
3rd-line status for refractory cases

74
Q

Clinical Pearls – Clinically significant drug interactions with antimicrobial agents

A

Antimicrobial agents
Azole antifungals
Macrolide antibiotics

75
Q

Clinical Pearls – Clinically significant drug interactions with antidepressants

A

Antidepressants
SSRIs
TCAs

76
Q

Clinical Pearls – Clinically significant drug interactions with misc

A

Cimetidine
INH
Rifampin

77
Q

Discontinuing AED therapy

A

Once a patient has been seizure-free for 2-4 years AED therapy may be successfully withdrawn

32 % recurrence in children, 39% in adults

78
Q

Discontinuing AED therapy advantages and disadvantages

A

Advantages
Cost
ADRs
Fewer lifestyle restrictions

Disadvantages
Reappearance may result in stat epi, loss of driving privileges, employment difficulties, or physical injury

79
Q

Generalized convulsive status epilepticus – GCSE

A

Only 40% of seizures that last 10-29 minutes stop without treatment

GCSE is very harmful to the brain

80
Q

Fosphenytoin–serum concentrations

A

Serum concentrations NOT clinically valuable
Cross-reacts with some phenytoin immunoassays causing an overestimation of phenytoin concentration
Check levels 2 hours after IV and 4 hours after IM

81
Q

Random facts about Fosphenytoin

A

IM only if IV access is not possible
Does NOT contain propylene glycol—good thing and is advantages over phenytoin

Decreased frequency of ECG and BP changes

Side effects such as paresthesia and pruritus of the face and groin not hypersensitivity and will go away

82
Q

IV Phenytoin (3)

A

Lower doses for the elderly, higher for the obese

Maintenance doses should be started within 12-24 hours of the loading dose

Contains 40% propylene glycol
Can cause hypotension and cardiac arrhythmias

83
Q

Treatment algorithm, early-established 0-10 min

A

0-10 minutes

IV lorazepam/ativan (first line!) 1 dose and then 2nd dose if needed

84
Q

Treatment algorithm, early-established 10-30 min

A

10-30 minutes

IV phenytoin or fosphenytoin

85
Q

Treatment algorithm, early-established 30-60 min

A

30-60 minutes
Additional dose of hydantoin 5 mg/kg
IV phenobarbital 20 mg/kg at a rate of 100 mg/min

86
Q

Treatment algorithm,refractory >60 minutes (10-15% GCSE) (3)

A

Additional dose of phenobarbital 10 mg/kg (every hour until seizure stops)
OR

IV valproate 15-25 mg/kg followed by 1-4 mg/kg/hour

OR

General anesthesia

87
Q

3 types of General Anethesia

A

IV midazolam works really well, short half life cont infusion, tachyphylaxis can occur
IV pentobarbital
IV propofol expensive

88
Q

GCSE – Nonpharmacologic therapy (4)

A

IV Glucose
Hypoglycemia may precipitate stat epi

IV Thiamine
Administered before the glucose to avoid Wernicke’s encephalopathy in alcoholics

Vital signs

Airway, ventilation

89
Q

Midazolam (4)

A

Diffuses rapidly into the brain

Extremely short half life  Must be given via continuous infusion

IM or buccal administration if IV access not possible
IM midazolam has more reliable absorption than IM lorazepam or IM diazepam

90
Q

Which Benzo has Peak concentrations in the brain the fastest

A

Diazepam

91
Q

Which Benzo has Rapid redistribution into fat

A

Lorazepam

92
Q

Which Benzo has longer duration of action?

A

Lorazepam

93
Q

Which Benzo has a Higher affinity to BZD receptor?

A

Lorazepam

94
Q

What does diazepam have to be combined with to make it long lasting?

A

AED

Seizures- Pharm (1 decks)

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