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Neorologia > ASDs > Flashcards

ASDs Flashcards

1
Q

List the voltage gated Na+ Channel Blockers

A 
Phenytoin, Fosphenytoin
Carbamazepine, Oxcarbazepine
Valproic Acid
Lamotrigine
Topiramate
Zonisamide
Lacosamine
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2
Q

Which state is are the Na+ channels blocked during

A

Inactivated state

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3
Q

Phenytoin (Dilantin)

Indication

A

Focal seizures

Generalized tonic-clonic seizures

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4
Q

Phenytoin (Dilantin)

PK

A

Non-linear

  • With change in dose, t1/2 changes
  • Induces metabolic enzymes, different time to steady state based on dose

t 1/2 15-20 hrs

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5
Q

Phenytoin (Dilantin)

Metabolism

A

CYP2C9/19

Forms: Arene Oxide Active metabolite with ADRs

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6
Q

Phenytoin ADRs

A 
Nystagmus
Diplopia
Sedation
Gingival Hyperplasia** 
Hirsutism**

Long term:
Choreoathetosis, peripheral neuropathy

Severe:
Toxic epidermal necrolysis
SJS

**Common

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7
Q

Phenytoin (Dilantin)

Teratogenicity

A

Fetal Hydantoin Syndrome

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8
Q

Phenytoin (Dilantin)

DDIs

A

-High Plasma Protein Binding (Displacement issues)
-CYP2C9/19 inhibitors
(Cimetidine, Isoniazid, Sulfonamides, Valproic Acid)
-CYP2C9/19 Inducers
(Barbiturates, ChronicEtOH, Carbamazepine, Rifampin)
-Drugs that decrease absorption (Antacids)

-Phenytoin induces CYP3A4, CYP2C, CYP2D

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9
Q

Carbamazepine (Tegretol, Carbatrol)

MOA

A

Na+ channel blocker

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10
Q

Phenytoin (Dilantin)

MOA

A

Voltage dependent Na+ channel blocker

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11
Q

Carbamazepine (Tegretol, Carbatrol)

PK: t1/2 and metabolism

A

t 1/2: 12-30 h (~15 for long term)

Metabolized by CYP3A4 (auto induction), CYP2C9/19

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12
Q

Carbamazepine (Tegretol, Carbatrol)

Indication

A
  • All seizure types except absence seizures

- Temperal lobe epilepsy

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13
Q

Carbamazepine (Tegretol, Carbatrol)
ADRs

BBW, Dose Related, Dose Unrelated, and Long-term Use

A

BBW: Leukopenia

Dose related: 
Fatigue, sedation
Nystagmus
Dilopia
Nausea
Ataxia

Dose Unrelated:
Rash & SJS
Teratogenicity

Longterm:
Seizure freq. increased
Aplastic anemia
Hypersensitivity

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14
Q

Carbamazepine (Tegretol, Carbatrol)

DDIs

A

-Strong CYP3A4 inducer
Other ASDs, Oral Contraceptives, Warfarin, Corticosteroids.

-CYP3A4 inhibitors
Valproate, Cimetidine, Erythromycin

-CYP3A4 inducers
Phenytoin, Carbamazepine, primidone, phenobarbital, Ethosuximide

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15
Q

Oxcarbazepine (Trileptal)

MOA and Indication

A

Same as Carbamazepine

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16
Q 
Oxcarbazepine (Trileptal)
PK
t1/2
t1/2 metabolites
Elimination
A

Oxcarbazepine : 1-2 h
Active metabolites : 8-12 h

Glucuronide (Urinary)

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17
Q

Oxcarbazepine (Trileptal)
ADRs
Dose related
Dose un-related

A

Less common, less severe

Dose related: Somnolence, dilopia, ataxia

Dose-unrelated: Rash, hyponatremia

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18
Q

Oxcarbazepine (Trileptal)

DDIs

A

WeakCYP3A4 induction:

Less affected by CYP3A4 modulation

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19
Q 
Valproic Acid (Depakote, Depakene)
MOAs (3)
A
  • Na channel blocker
  • Stimulates GABA synthesis
  • Inhibits GABA transaminase
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20
Q 
Valproic Acid (Depakote, Depakene)
Indication
A

Most seizure types INCLUDING absence seizures

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21
Q

Lamotrigine (Lamictal)

MOA

A

Na+ Channel Blocker

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22
Q

Lamotrigine (Lamictal)

Indication

A

All seizure types

Generalized seizures in children with absence attacks

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23
Q

Lamotrigine (Lamictal)
PK
t1/2
Elimination

A

25 h

Glucuronide conjugation

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24
Q

Lamotrigine (Lamictal)

ADRs

A

Headache, nausea, vomiting

Rash (SJS)

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25
Q

Lamotrigine (Lamictal)

DDIs

A

Hepatic inducers increase glucuronidation (Clearance)

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26
Q

Topiramate (Topamax)

MOAs (3)

A
  • Na+ blocker
  • Augments GABA at GABAaR
  • Blockatde of Glutamate receptors (Kainate, AMPA)
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27
Q

Topiramate (Topamax)

Indications

A

Focal Seizures

Generalized tonic-clonic seizures

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28
Q

Topiramate (Topamax)
PK
t1/2

A

20-30 h

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29
Q

Topiramate (Topamax)

ADRs

A

Sedation, cognitive slowing, confusion

Fetal malformations

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30
Q

Topiramate (Topamax)

DDIs

A

Carbamazepine, Phenytoin increase topiramate metabolism

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31
Q

Zonisamide (Zonegran)

MOAs (2)

A

Na+ channel blocker

T-type Ca2+ channel blocker

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32
Q

Zonisamide (Zonegran)

Indication

A

Focal Seizures

33
Q

Zonisamide (Zonegran)
PK
t1/2
metabolism

A

> 60 h

Partially by CYP3A4

34
Q

Zonisamide (Zonegran)

ADRs

A

Dizzienes, ataxia
Somnolence/Insomnia
Cognitive problems
Rash (fatal)

35
Q

Zonisamide (Zonegran)

DDIs

A

-Phenytoin, Carbamazepine (CYP3A4 inducers)

Valproic Acid, Cimetidine, Erythromycin (CYP3A4 inhibitors)

Sufonamide hypersensitivity (contraindicated)

36
Q

Lacosamide (Vimpat)

MOA

A

Enhances slow inactivation of Na+ channels

37
Q

Lacosamide (vimpat)

Indication

A

Adjunctive therapy for focal-onset seizures

38
Q

Lacosamide (Vimpat)
PK
t1/2
metabolism

A

12-16 h

CYP2C19

39
Q

Lacosamide (Vimpat)

DDIs

A

N/a?

CYP2C19 Inducers?
Phenytoin and Carbamazepine?

40
Q

Gabapentin (Neurontin, Gralise)

MOAs(2)

A

Ca2+ Channel Blocker –> Decrease glutamate release

GABAergic –> Increases release of GABA

41
Q

Gabapentin (Neurontin, Gralise)

Indication

A

Focal Seizures

42
Q 
Gabapentin (Neurontin, Gralise)
PK
t1/2 
PPB
Metabolism
A

~6 h
0%
hardly metabolized

43
Q

Gabapentin (Neurontin, Gralise)

ADRs

A

Sedation, Somnolence, Dizziness, Fatigue
Nystagmus
Ataxia

44
Q

Gabapentin (Neurontin, Gralise)

DDIs

A

None (Based on PK)

45
Q

Pregabalin (Lyica)

MOA

A

Ca++ channel blocker –> decreased Glu release

46
Q

Pregabalin (Lyrica)

Indication

A

Focal seizures

47
Q 
Pregabalin (Lyrica) 
PK
t1/2
PPB
Metabolism
A

~6 h
0%
hardly metabolized

48
Q

Pregabalin (Lyrica)

A 
SEDATION, somnolence, dizziness
Headache
WEIGHT GAIN
Dry mouth
Blurred vision
49
Q

Pregabalin (Lyrica)

DDIs

A

N/a

50
Q

Tiagabine (Gabitril)

MOA

A

GABA reuptake inhibitor

51
Q

Tiagabine (Gabitril)

Indication

A 
Focal seizures
(Mainly Ad on, no longer 1st line)
52
Q

Tiagabine (Gabitril)
PK
t1/2
metabolism

A

7h

CYP3A

53
Q

Tiagabine (Gabitril)

ADRs

A

Sedation, dizzines, somnolence
Difficulty with concentration
abdominal Pain

**Can actually induce status epilepticus!! (rare)

54
Q

Tiagabine (Gabitril)

DDIs

A

CYP3A inducers/inhibitors

55
Q

Vigabatrin (Sabril)

MOA

A

GABA Transaminase Inhibitor

Transaminase converts GABA to glutamate (in the synaptic cleft) which then is converted to glutamine in the glia to be recycled to glutamate in glutaminergic neurons

56
Q

Vigabatrin (Sabril)

Indication

A

Adjunct for infantile spasms,
Frefractory complex focal seizures,
West Syndrome

57
Q 
Vigabatriin (Sabril) 
PK
t1/2
PPB
Elimination
A

5-7 h
0%
Renal

58
Q

Vigabatrin (Sabril)

ADRs

A

Sedation, fatigue

  • Depresion, psychotic disurbances
  • WHITE MATTTER LESIONS (30%)
  • PROGRESSIVE PERMANENT BILATERAL VISION LOSS (30-50%!!!!!)

–> Only available through “SHARE”

59
Q

Vigabatrin (Sabril)

DDIs

A

Decreases phenytoinn Cp by 20-30%

Minimal due to PK

60
Q

Phenobarbital (Luminal)

MOA

A

GABAa Receptor agonist

61
Q

Phenobarbital (Luminal)

Indication

A

All seizure types except absence seizures

62
Q 
Phenobarbital (Luminal)
PK
t1/2
PPB
Elimination
A

> 60 h
40-60%
Renal excretion of non-metabolized drug

*Strong induction of CYP2C and CYP3A (DDIs)

63
Q

Phenobarbital (Luminal)

ADRs

A

Sedation, tolerance develops
Nystagmus, Ataxia
Learning Difficulties (Don’t give to children)

64
Q

Phenobarbital (Luminal)

DDIs

A

Induces CYP2C and CYP3A, induces metabolism of other drugs

65
Q

Benzodiazepines

Drugs

A

Diazepam (Valium, Diastat)
Clonazepam (Klonopin)
Lorazepam (Ativan)
Clobazam (Onfi)

66
Q

Benzodiazepines

MOA

A

GABAa Receptor

67
Q

Benzodiazepines

Indications (Drugs specific)

A 
Diazepam - Status Epilepticus
Clonazepam - Long-term (also absence)
Lorazepam - Status Epilepticus
Clorazepate - Long term
Clobazam Lennox-Gastaut Syndrome (Adjunct)
68
Q

Benzodiazepines
PK
t1/2
PPB

A

20-50 h

85-99%

69
Q

Benzodiazepines

ADRs

A

Tolerance (50%, 1-6 months)!!
CNS depression, STRONG Sedation, Lethargy
Aggressiveness (25%)
Withdrawal Syndrom

70
Q

Benzodiazepines

DDIs

A

GABAa Acting substances

71
Q

ASDs for for focal seizures and generalized tonic-clonic seizures

A

Carbamazepine
Phenytoin
Valproic Acid
Phenobarbital

Lamotrigine, Oxcarbazepine, Felbamate, Gabapentin, Pregabalin, Vigabatrin, Lacosamide, Levitiracetam, Tiagabine, Topiramate

72
Q

ASDs for Gernalized absence, myclonic, or atonic seizures

A

Valproic Acid
Ethosuximide
Clonazepam
Lamotrigene

73
Q

ASDs for status epilepticus

A

Diazepam

Lorazepam

74
Q

ASDs with weight gain

A 
Valproate (common)
Carbamazepine
Gabapentin
Pregabalin
Perampanel
75
Q

ASDs with weight los

A

Topiramate
Felbamate
Zonisamide

76
Q

ASDs that are weight neutral

A

Phenytoin
Lamotrigine
Lacosamide
Levetiraetam

77
Q

Hormonal contraception DDIs

CYP3A4

A 
Carbamazepine
Oxcarbazepine
Felbamate
Topiramate
Phenytoin
Phenobarbital
78
Q

ASDs with Teratogenic effects

A

Phenytoin
Phenobarbital
Valproic Acid
Carbamazepine

79
Q

Which ASD probably transfers to breast milk

A

Levetiracetam

Neorologia (12 decks)

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