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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
What 3 things need to be monitored for Phenytoin?
CBC LFTs Albumin
26
2 Risks with taking phenytoin?
Risk of suicidal ideation Pregnancy Category D
27
What serum monitoring due to a therapeutic index for phenytoin
10-20 mcg/mL (total)
28
What are some adverse affects of Phenytoin?
``` 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 ```
29
What are 3 dose related adverse effects for phenytoin?
20 mcg/ml: Nystagmus 30 mcg/ml: Ataxia, diplopia, slurred speech >40 mcg/ml: Sedation, lethargy, tremor
30
Drugs that increase phenytoin levels?
acute alcohol intake, salicylates, estrogens, H2-antagonists
31
Drugs that decrease phenytoin levels?
carbamazepine, chronic alcohol abuse, antacids with calcium, phenobarbital, rifampin
32
Phenytoin and Warfarin--> protein binding
an immediate reaction | Phenytoin can displace warfarin which may result in a rapid INCREASE in INR
33
Phenytoin and Warfarin-->CYP 2C9 induction
after prolonged administration | Phenytoin induces the metabolism of warfarin which may result in a DECREASE in INR
34
Phenytoin and Warfarin--> Depletion of Vitamin-K dependent clotting factors
Warfarin inhibits the synthesis of clotting factors Phenytoin may also deplete these clotting factors May result in a further INCREASE in INR
35
Carbamazepine – CBZ Advantages and Disadvantages
Advantages Well studied Disadvantages Active metabolite Auto-inducer, drug interactions**** CNS side effects****
36
Carbamazepine – CBZ is indicated for?
``` Primary generalized (in a non-emergent situation) Partial seizures (newly diagnosed) ```
37
Carbamazepine-- 3 things to monitor
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
38
Carbamazepine have 5 ADR's
``` Diplopia Dizziness, unsteadiness Drowsiness, lethargy Nausea, GI upset Rash ```
39
Carbamazepine is contraindicated with?
Hypersensitivity to TCAs | Bone marrow suppression
40
Carbamazepine Black Box Warning
Blood dyscrasias | Patients of Asian descent should be screened for HLA-B*1502 allele prior to initiating therapy
41
Oxcarbazepine (Trileptal®) Advantages and Disadvantages
Advantages Comparable efficacy to phenytoin, valproic acid, and CBZ, but may be better tolerated Disadvantages Hyponatremia Drug interactions
42
Oxcarbazepine (Trileptal®) indicated for?
Partial seizures (monotherapy or adjunctively) GTC seizures Pregnancy Category C
43
Oxcarbazepine (Trileptal®) CNS related ADR's
Cognitive symptoms, including difficulty with concentration, psychomotor slowing, and speech or language problems Somnolence or fatigue Coordination abnormalities, including ataxia and gait disturbances
44
Topiramate (Topamax®) Advantages and Disadvantages
Advantages Few drug interactions Weight loss? Disadvantages Cognitive functioning impairment Kidney stones Weight loss?
45
Topiramate (Topamax®) common ADR's
Cognitive impairment - Poor concentration, confusion, word-finding difficulties Ataxia, dizziness Somnolence Weight loss
46
Topiramate (Topamax®) Drug interactions
``` OCs may be less effective- higher estrogen doses may be required Digoxin - ↓ concentration Valproic acid - ↑ risk of hyperammonemia Phenytoin, CBZ, barbiturates CNS depressants ```
47
Lamotrigine (Lamictal®) Advantages and Disadvantages
Advantages Not highly protein bound Does not cause weight gain Disadvantages Rash Drug interactions
48
Lamotrigine (Lamictal®) alternative for what type of seizures?
absent seizures
49
Lamotrigine (Lamictal®) ADR
``` Coordination abnormalities Anxiety, mania Diplopia Insomnia Drowsiness, fatigue hypersensitivity--> may cause SJS ```
50
Agents that cause visual abnormalities (6)
Lacosamide Lamotrigine Phenytoin Pregabalin Tiagabine Vigabatrin
51
4 anticonvulsants that cause weight loss
Ethosuximide Felbamate Topiramate Zonisamde
52
4 anticonvulsants that cause weight gain
Gabapentin Pregabalin Valproic Acid Vigabatrin
53
Valproic Acid advantages and disadvantages?
Advantages Well studied Multiple dosage forms Disadvantages Side effect profile Drug interactions Enzyme inhibitor
54
Valproic Acid serum monitoring
Serum monitoring not typically required but can be used to determine toxicity and dosage adjustments 50-150 mcg/mL
55
Valproic Acid common ADR's
``` Nausea, vomiting, abdominal pain, heartburn Sedation Fine hand tremor Weight gain and increased appetite Hair loss Hepatotoxicity Thrombocytopenia pregnancy cat D ```
56
Gabapentin – Neurontin®
Advantages No known drug interactions Disadvantages Very high doses required for seizure control Increased dosing frequency
57
Gabapentin – Neurontin® Pharmacokinetics
Not metabolized (renally excreted unchanged) Does not induce hepatic enzymes Half-life: 5-8 hours
58
Gabapentin – Neurontin® ADR
``` Somnolence Ataxia Tremor Dizziness Headache Pregnancy Cat C ```
59
Levetiracetam – Keppra® Advantages and Disadvantages
Advantages No known drug interactions Various dosage forms Pediatric use Disadvantages Limited indications
60
Levetiracetam – Keppra® Common ADR's
Somnolence, asthenia, dizziness, vertigo, headaches | Not dependent on dose or dose titration
61
Pregabalin – Lyrica® Advantages and Disadvantages
Advantages No known drug interactions Disadvantages Brand name only, expensive Schedule V
62
Pregabalin – Lyrica® Common ADR
``` Dizziness, ataxia Somnolence Peripheral edema, Weight gain Headache pregnancy Cat C ```
63
Tiagabine – Gabitril®
``` adjunct therapy Half-life = 6.7 hours Extensively metabolized by CYP3A4 highly protein bound Titration is extremely slow*** ```
64
Tiagabine – Gabitril® ADR
``` Dizziness Fatigue Generalized muscle weakness Nervousness Tremor Abnormal thinking Depression Aphasia Encephalopathy prey cat C ```
65
Zonisamide – Zonegran® ADR
Fatigue, dizziness, ataxia, somnolence, anorexia/weight loss, psychomotor slowing Pregnancy Category C
66
Phenobarbital – Luminal® Advantages and Disadvantages
Indicated for: All seizure disorders! Advantages Oldest anti-epileptic drug Broad-spectrum Disadvantages Pan-inducer Toxicity
67
Phenobarbital – Luminal® Therapeutic levels
Therapeutic levels 15-40 mcg/ml adjust for renal and hepatic dysfunction
68
Phenobarbital – Luminal® ADR
Dependence CNS depression pret cat D
69
Phenobarbital- Luminal withdrawal symptoms
convulsions and delirium
70
Primidone – Mysoline® (5)
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
Ethosuximide – Zarontin® indicated for?
FDA approved for absence seizures**** First line for absent seizures**** BID
72
Ethosuximide – Zarontin® Dose related adverse effects Drug interactions
Not protein bound Drug interactions Clearance ’d by valproic ``` Common dose-related adverse effects Gastric distress Fatigue Headache Dizziness Hiccups Euphoria ```
73
Felbamate – Felbatol® indicated for?
Effective for partial seizures Causes aplastic anemia and severe hepatitis 3rd-line status for refractory cases
74
Clinical Pearls -- Clinically significant drug interactions with antimicrobial agents
Antimicrobial agents Azole antifungals Macrolide antibiotics
75
Clinical Pearls -- Clinically significant drug interactions with antidepressants
Antidepressants SSRIs TCAs
76
Clinical Pearls -- Clinically significant drug interactions with misc
Cimetidine INH Rifampin
77
Discontinuing AED therapy
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
Discontinuing AED therapy advantages and disadvantages
Advantages Cost ADRs Fewer lifestyle restrictions Disadvantages Reappearance may result in stat epi, loss of driving privileges, employment difficulties, or physical injury
79
Generalized convulsive status epilepticus – GCSE
Only 40% of seizures that last 10-29 minutes stop without treatment GCSE is very harmful to the brain
80
Fosphenytoin--serum concentrations
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
Random facts about Fosphenytoin
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
IV Phenytoin (3)
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
Treatment algorithm, early-established 0-10 min
0-10 minutes | IV lorazepam/ativan (first line!) 1 dose and then 2nd dose if needed
84
Treatment algorithm, early-established 10-30 min
10-30 minutes | IV phenytoin or fosphenytoin
85
Treatment algorithm, early-established 30-60 min
30-60 minutes Additional dose of hydantoin 5 mg/kg IV phenobarbital 20 mg/kg at a rate of 100 mg/min
86
Treatment algorithm, refractory >60 minutes (10-15% GCSE) (3)
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
3 types of General Anethesia
IV midazolam works really well, short half life cont infusion, tachyphylaxis can occur IV pentobarbital IV propofol expensive
88
GCSE – Nonpharmacologic therapy (4)
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
Midazolam (4)
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
Which Benzo has Peak concentrations in the brain the fastest
Diazepam
91
Which Benzo has Rapid redistribution into fat
Lorazepam
92
Which Benzo has longer duration of action?
Lorazepam
93
Which Benzo has a Higher affinity to BZD receptor?
Lorazepam
94
What does diazepam have to be combined with to make it long lasting?
AED

Seizures- Pharm (1 decks)

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