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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
Clonazepam: MOA, pharmokinetics
enhance GABA receptor response >80% bioavailability
26
Clonazepam: clinical application
generalized absence focal/generalized myoclonic infantile spasms
27
Clonazepam: ADEs
sedation
28
Topiramate: MOA, pharmokinetics
AMPA receptor inhibitor blocks voltage gated Na enhances GABA activity hepatic and renal clearance
29
Topiramate: clinical application
generalized tonic clonic generalized absence focal aware/impaired migraine
30
Topiramate: ADEs
``` COGNITIVE SLOWING CONFUSION sleepiness GI symptoms metabolic acidosis pregnancy category D ```
31
Medications to avoid with absence seizures
carbamazepine vigabatrin gabapentin tiagabine they aggravate absence seizures
32
Medications that are ineffective for absence seizures
phenytoin | phenobarbital
33
Tonic Clonic Seizures: treatment
``` topiramate lamotrigine levetiracetam perampanel phenytoin carbamazepine phenobarbital valproic acid ```
34
Levetiracetam: MOA, pharmokinetics
blocks synaptic release machinary SV2A dec glutamate minimal drug reactions
35
Levetiracetam: clinical application
generalized tonic clonic | focal aware/impaired
36
Levetiracetam: ADEs
``` BEHAVIORAL PROBLEMS HEADACHE sedation seizures - focal onset weakness ```
37
Focal Onset Seizures: treatment
``` Carbamazepine Lacosamide Phenobarbital Phenytoin Topiramate Valproic Acid ``` ``` Alternatives: Oxcarbazepine Gabapentin Lamotrigine Levetiracetam Vigabatrinb Zonisamideb ```
38
Carbamazepine: MOA, pharmokinetics
blocks voltage gated Na channels dec glutamate many drug interactions induces own metabolism
39
Carbamazepine: clinical application
generalized tonic clonic | focal aware/impaired
40
Carbamazepine: ADEs
SERIOUS DERMATOLOGIC REACTIONS AND HLA B1502 ALLELE IN ASIANS APLASTIC ANEMIA AGRANULOCYTOSIS ``` ATAXIA DIPLOPIA HYPONATREMIA METABOLIC BONE DISEASE nausea ```
41
Lacosamide: MOA, pharmokinetics
blocks voltage gated Na channels dec glutamate minimal drug interactions
42
Lacosamide: clinical application
generalized tonic clonic | focal aware/impaired
43
Lacosamide: ADEs
``` dizziness headache nausea inc lft's SMALL INC IN PR INTERVAL ```
44
Phenytoin: MOA, pharmokinetics
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
Phenytoin: clinical application
generalized tonic clonic | focal aware/impaired
46
Phenytoin: ADEs
``` ATAXIA NYSTAGMUS GINGIVAL HYPERPLASIA HIRSUTISM NEUROPATHY FOLATE DEFICIENCY METABOLIC BONE DISEASE vitamind D ```
47
Phenobarbital: MOA, pharmokinetics
enhances GABA receptor responses long half life P450 inducer many interactions
48
Phenobarbital: clinical applications
generalized tonic clonic | focal aware/impaired
49
Phenobarbital: ADEs
``` SEDATION INTELLECTUAL BLUNTING METABOLIC BONE DISEASE BEHAVIOR CHANGES ataxia vitamin D ```
50
Gabapentin: MOA, pharmokinetics
blocks synaptic release machinery Α2δ dec glutamate variable bioavailability renal elimination
51
Gabapentin: clinical application
generalized tonic clonic | focal aware/impaired
52
Gabapentin: ADEs
ATAXIA dizziness SOMNOLENCE WEIGHT GAIN
53
Pregabalin: MOA, pharmokinetics
blocks synaptic release machinery Α2δ dec glutamate renal elimination
54
Pregabalin: clinical application
focal aware/impaired
55
Pregabalin: ADEs
ATAXIA dizziness SOMNOLENCE WEIGHT GAIN
56
Vigabatrin: MOA, pharmokinetics
GABA transaminase enhancing GABA activation renal elimination
57
Vigabatrin: clinical application
focal aware/impaired
58
Vigabatrin: ADEs
``` PERMANENT VISION LOSS drowsiness dizziness psychosis ocular effects ```
59
Perampanel: MOA, pharmokinetics
blocks postsynaptic ionotropic glutamate receptors AMPA dec glutamate multiple metabolites with long half lives substantial interactions inc clearance by CYP3A
60
Perampanel: clinical application
focal aware/impaired
61
Perampanel: ADEs
``` SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS dizziness somnolence headache psychiatric syndromes ```
62
Tiagabine: MOA, pharmokinetics
GAT1 GABA transporter enhancing GABA activation some drug interactions
63
Tiagabine: clinical application
focal aware/impaired
64
Tiagabine: ADEs
``` dizziness nervousness CONCENTRATION AND ATTENTION DIFFICULTY BEHAVIORAL DISTURBANES INC APPETITE ```
65
Myoclonic Seizures: treatment
levetiracetam ``` Alternatives: clonazepam topiramate valproic acid zonisamide ```
66
Zonisamide: MOA, pharmokinetics
blocks Na and Ca channels **does NOT affect GABA activity hepatic and renal clearance
67
Zonisamide: clinical application
generalized tonic clonic focal aware/impaired focal/generalized myoclonic
68
Zonisamide: ADEs
``` sedation COGNITIVE SLOWING PARESTHESIA RASH (sulfa based drug) KIDNEY STONES OLIGOHYDROSIS (low amniotic fluid) ```
69
Phenytoin: interactions
``` phenobarbital carbamazepine felbamate oxcarbazepine topiramate ``` ``` fluoxetine fluconazole digoxin isoniazid oral contraceptives ```
70
Phenobarbital: interactions
``` valproate carbamazepine felbamate phenytoin lamotrigine ``` cyclosporine nifedipine theophylline verapamil
71
Ethosuximide: interactions
valproate phenobarbital phenytoin carbamazepine rifampicin
72
Carbamazepine: interactions
``` phenytoin carbamazepine valproate phenobarbital primidone ``` fluoxetine verapamil macrolide antibiotics isoniazid
73
Valproate: interactions
``` phenobarbital phenytoin carbamazepine lamotrigine felbamate ethosuximide primidone ``` Rifampin
74
Lamotrigine: interactions
``` valproate carbamazepine oxcarbazepine phenytoin phenobarbital primidone succinimides topiramate ``` sertraline
75
Rufinamide: interactions
Not metabolized via P450 enzymes, but antiseizure drug interactions may be present
76
Tiagabine: interactions
phenobarbital phenytoin carbamazepine primidone
77
Topiramate: interactions
phenytoin carbamazepine lamotrigine oral contraceptives lithium?
78
Drugs with minimal or rare interactions
gabapentin levetiracetam pregabalin vigabatrin
79
Cannabidiol
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
Stiripentol
indicated for patients with Dravet syndrome who also take clobazam
81
Cannabidiol, Stiripentol
effective in dec drop seizures

PHA 550 (26 decks)

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