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PHA 550 > Antiseizure Drugs > Flashcards

Antiseizure Drugs Flashcards

1
Q

What is the difference between epilepsy and seizures?

A

duration of symptoms

Epilepsy: chronic, recurrent
Seizure: finite, resolves

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2
Q

Seizure

A

transient disturbance of cerebral function due to an abnormal paroxysmal neuronal discharge in the brain

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3
Q

Seizure Classification: Focal Onset

A

aware or impaired awareness

motor or nonmotor onset

focal to bilateral tonic clonic

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4
Q

Seizure Classification: Generalized Onset

A

Motor

  • tonic clonic
  • other motor

Nonmotor (absence)

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5
Q

Seizure Classification: Unknown Onset

A

unwitnessed

Motor

  • tonic clonic
  • other motor

Nonmotor

Unclassified

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6
Q

What drugs lower the seizure threshold?

A 
theophylline
alcohol
high dose phenothiazines
antidepressants (especially buproprion)
street drugs
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7
Q

Epilepsy: Risk Factors

A

premature birth w/ small gestational weight

perinatal injury (anoxia)

history of alcohol withdrawal seizures

history of febrile seizures

family history of seizures

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8
Q

Do we initiate therapy in a patient with:
no risk factors
normal MRI
normal EEG?

A

probability of seizure recurrence:
first year: <10%
end of second year: ~21%

weigh the risks and benefits

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9
Q

Do we initiate therapy in a patient if risk factors are present?

A

probability of seizure recurrence:
first year: 26%
end of second year: 41%

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10
Q

Do we initiate therapy in a patient with 2+ unprovoked seizures?

A

Yes

should be started on ASDs

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11
Q

Treatment Considerations

A

establish seizure type and epilepsy classification

age, gender, comorbidities, susceptibility to ADEs, other medications, adherence, insurance coverage, need for quick therapeutic levels

monotherapy is preferred

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12
Q

Factors favoring successful withdrawal of ASDs

A

seizure free for 2-4 years

complete seizure control w/in 1 year of onset

onset of seizures after 2 but before 35 years of age

AND

normal neurologic examination and EEG

you have to taper

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13
Q

Three Proposed Mechanisms of Antiseizure Drug Therapy

A

modification of ionic conductance (Na, Ca, K)

diminution of usually glutamatergic (excitatory) transmission

enhancement of GABAergic (inhibitory) transmission

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14
Q

Main Effect of Antiseizure Drug Therapy

A

inhibition of local generation of seizure discharges

  • reduced ability of neurons to fire APs at high rate
  • reduced neuronal synchronization
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15
Q

Generalized Absence: treatment

A

ethosuxumide
lamotrigine
valproic acid

alternatives for refractory:
clonazepam
topiramate

**gabapentin is ineffective

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16
Q

Ethosuximide: MOA, pharmokinetics

A

blocks voltage gated Ca channels

dec glutamate

long half life

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17
Q

Ethosuximide: clinical application

A

generalized absence

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18
Q

Ethosuximide: ADEs

A 
gi distress
ataxia
drowsiness
HEADACHE
BLOOD DYSCRASIAS 
rash
behavior changes
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19
Q

Lamotrigine: MOA, pharmokinetics

A

blocks voltage gated Na channels

dec glutamate

many drug interactions

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20
Q

Lamotrigine: clinical application

A

generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic
generalized absence

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21
Q

Lamotrigine: ADEs

A 
SERIOUS SKIN RASH (start low go slow)
DIPLOPIA
headache
dizziness
hemophagocytic lymphohistiocytosis
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22
Q

Valproate/Valproic Acid: MOA, pharmokinetics

A

inc/enhance GABA or mimic at post synaptic receptors

many drug interactions

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23
Q

Valproate/Valproic Acid: clinical application

A

generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic
generalized absence

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24
Q

Valproate/Valproic Acid: ADEs

A 
HEPATOTOXICITY
TERATOGENIC
PANCREATITIS
nausea
ALOPECIA
weight gain
vitamin D
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25
Q

Clonazepam: MOA, pharmokinetics

A

enhance GABA receptor response

> 80% bioavailability

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26
Q

Clonazepam: clinical application

A

generalized absence
focal/generalized myoclonic
infantile spasms

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27
Q

Clonazepam: ADEs

A

sedation

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28
Q

Topiramate: MOA, pharmokinetics

A

AMPA receptor inhibitor
blocks voltage gated Na
enhances GABA activity

hepatic and renal clearance

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29
Q

Topiramate: clinical application

A

generalized tonic clonic
generalized absence
focal aware/impaired
migraine

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30
Q

Topiramate: ADEs

A 
COGNITIVE SLOWING
CONFUSION
sleepiness
GI symptoms
metabolic acidosis
pregnancy category D
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31
Q

Medications to avoid with absence seizures

A

carbamazepine
vigabatrin
gabapentin
tiagabine

they aggravate absence seizures

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32
Q

Medications that are ineffective for absence seizures

A

phenytoin

phenobarbital

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33
Q

Tonic Clonic Seizures: treatment

A 
topiramate
lamotrigine
levetiracetam 
perampanel
phenytoin
carbamazepine
phenobarbital
valproic acid
34
Q

Levetiracetam: MOA, pharmokinetics

A

blocks synaptic release machinary SV2A

dec glutamate

minimal drug reactions

35
Q

Levetiracetam: clinical application

A

generalized tonic clonic

focal aware/impaired

36
Q

Levetiracetam: ADEs

A 
BEHAVIORAL PROBLEMS
HEADACHE
sedation
seizures - focal onset
weakness
37
Q

Focal Onset Seizures: treatment

A 
Carbamazepine
Lacosamide
Phenobarbital
Phenytoin
Topiramate
Valproic Acid
Alternatives: 
Oxcarbazepine
Gabapentin
Lamotrigine
Levetiracetam
Vigabatrinb
Zonisamideb
38
Q

Carbamazepine: MOA, pharmokinetics

A

blocks voltage gated Na channels

dec glutamate

many drug interactions

induces own metabolism

39
Q

Carbamazepine: clinical application

A

generalized tonic clonic

focal aware/impaired

40
Q

Carbamazepine: ADEs

A

SERIOUS DERMATOLOGIC REACTIONS AND HLA B1502 ALLELE IN ASIANS
APLASTIC ANEMIA
AGRANULOCYTOSIS

ATAXIA
DIPLOPIA
HYPONATREMIA
METABOLIC BONE DISEASE
nausea
41
Q

Lacosamide: MOA, pharmokinetics

A

blocks voltage gated Na channels

dec glutamate

minimal drug interactions

42
Q

Lacosamide: clinical application

A

generalized tonic clonic

focal aware/impaired

43
Q

Lacosamide: ADEs

A 
dizziness
headache
nausea
inc lft's
SMALL INC IN PR INTERVAL
44
Q

Phenytoin: MOA, pharmokinetics

A

blocks voltage gated Na channels

dec glutamate

variable absorption
dose dependent elimination
protein binding
many drug interactions

BOX WARNING: cardiovascular risk associated w/ rapid infusion

45
Q

Phenytoin: clinical application

A

generalized tonic clonic

focal aware/impaired

46
Q

Phenytoin: ADEs

A 
ATAXIA
NYSTAGMUS
GINGIVAL HYPERPLASIA
HIRSUTISM
NEUROPATHY
FOLATE DEFICIENCY
METABOLIC BONE DISEASE
vitamind D
47
Q

Phenobarbital: MOA, pharmokinetics

A

enhances GABA receptor responses

long half life
P450 inducer
many interactions

48
Q

Phenobarbital: clinical applications

A

generalized tonic clonic

focal aware/impaired

49
Q

Phenobarbital: ADEs

A 
SEDATION
INTELLECTUAL BLUNTING
METABOLIC BONE DISEASE
BEHAVIOR CHANGES
ataxia
vitamin D
50
Q

Gabapentin: MOA, pharmokinetics

A

blocks synaptic release machinery Α2δ

dec glutamate

variable bioavailability
renal elimination

51
Q

Gabapentin: clinical application

A

generalized tonic clonic

focal aware/impaired

52
Q

Gabapentin: ADEs

A

ATAXIA
dizziness
SOMNOLENCE
WEIGHT GAIN

53
Q

Pregabalin: MOA, pharmokinetics

A

blocks synaptic release machinery Α2δ

dec glutamate

renal elimination

54
Q

Pregabalin: clinical application

A

focal aware/impaired

55
Q

Pregabalin: ADEs

A

ATAXIA
dizziness
SOMNOLENCE
WEIGHT GAIN

56
Q

Vigabatrin: MOA, pharmokinetics

A

GABA transaminase enhancing GABA activation

renal elimination

57
Q

Vigabatrin: clinical application

A

focal aware/impaired

58
Q

Vigabatrin: ADEs

A 
PERMANENT VISION LOSS
drowsiness
dizziness
psychosis
ocular effects
59
Q

Perampanel: MOA, pharmokinetics

A

blocks postsynaptic ionotropic glutamate receptors AMPA

dec glutamate

multiple metabolites with long half lives

substantial interactions
inc clearance by CYP3A

60
Q

Perampanel: clinical application

A

focal aware/impaired

61
Q

Perampanel: ADEs

A 
SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
dizziness
somnolence
headache
psychiatric syndromes
62
Q

Tiagabine: MOA, pharmokinetics

A

GAT1 GABA transporter enhancing GABA activation

some drug interactions

63
Q

Tiagabine: clinical application

A

focal aware/impaired

64
Q

Tiagabine: ADEs

A 
dizziness
nervousness
CONCENTRATION AND ATTENTION DIFFICULTY
BEHAVIORAL DISTURBANES
INC APPETITE
65
Q

Myoclonic Seizures: treatment

A

levetiracetam

Alternatives:
clonazepam
topiramate
valproic acid
zonisamide
66
Q

Zonisamide: MOA, pharmokinetics

A

blocks Na and Ca channels

**does NOT affect GABA activity

hepatic and renal clearance

67
Q

Zonisamide: clinical application

A

generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic

68
Q

Zonisamide: ADEs

A 
sedation
COGNITIVE SLOWING
PARESTHESIA
RASH (sulfa based drug)
KIDNEY STONES
OLIGOHYDROSIS (low amniotic fluid)
69
Q

Phenytoin: interactions

A 
phenobarbital
carbamazepine
felbamate
oxcarbazepine
topiramate
fluoxetine
fluconazole
digoxin
isoniazid
oral contraceptives
70
Q

Phenobarbital: interactions

A 
valproate
carbamazepine
felbamate
phenytoin
lamotrigine

cyclosporine
nifedipine
theophylline
verapamil

71
Q

Ethosuximide: interactions

A

valproate
phenobarbital
phenytoin
carbamazepine

rifampicin

72
Q

Carbamazepine: interactions

A 
phenytoin
carbamazepine
valproate
phenobarbital
primidone

fluoxetine
verapamil
macrolide antibiotics
isoniazid

73
Q

Valproate: interactions

A 
phenobarbital 
phenytoin
carbamazepine
lamotrigine
felbamate
ethosuximide
primidone

Rifampin

74
Q

Lamotrigine: interactions

A 
valproate
carbamazepine
oxcarbazepine
phenytoin
phenobarbital
primidone
succinimides
topiramate

sertraline

75
Q

Rufinamide: interactions

A

Not metabolized via P450 enzymes, but antiseizure drug interactions may be present

76
Q

Tiagabine: interactions

A

phenobarbital
phenytoin
carbamazepine
primidone

77
Q

Topiramate: interactions

A

phenytoin
carbamazepine
lamotrigine

oral contraceptives
lithium?

78
Q

Drugs with minimal or rare interactions

A

gabapentin
levetiracetam
pregabalin
vigabatrin

79
Q

Cannabidiol

A

approved as adjunctive treatment for seizures related to Dravet and Lennox Gastaut syndromes

2+ years of age

assess ALT, AST, total bilirubin

interaction: CNS depressants

ADEs:
hepatic
dec appetite
drowsiness
anemia
infections
asthenia
80
Q

Stiripentol

A

indicated for patients with Dravet syndrome who also take clobazam

81
Q

Cannabidiol, Stiripentol

A

effective in dec drop seizures

PHA 550 (26 decks)

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