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Pharmacology > Anti-Epileptics > Flashcards

Anti-Epileptics Flashcards

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1
Q

Screening test for Absence seizure drugs

A

Pentylenetetrazol

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2
Q

Screening test for GTCS and complex partial seizure drugs

A

Maximal Electroshock Test

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3
Q

MOA of drugs identified by Maximal Electroshock Test

A

prolonged inactivation of VG Na channels

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4
Q

Drugs that inhibit presynaptic glutamate VG Na channels

A

Lancosamide
Lamotrigine
Carbamezapine
Phenytoin

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5
Q

Drugs that inhibit presynaptic glutamate VG Ca channels

A

Ethosuximide
Lamotrigine
Pregabalin
Gabapentin

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6
Q

Drugs that inhibit presynaptic glutamate K channels

A

Retigabine

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7
Q

Drugs that inhibit glutamate SV2A (synaptic vesicle protein)

A

Levetiracetam

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8
Q

Drugs that inhibit presynaptic glutamate CRMP-2

A

Lacosamide

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9
Q

Drugs that inhibit postsynaptic glutamate AMPA receptors

A

Phenobarbital
Topiramate
Lamotrigine

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10
Q

Drugs that inhibit postsynaptic glutamate NMDA receptors

A

Felbamate

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11
Q

Drug that inhibits GAT-1

A

Tiagabine

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12
Q

Drug that inhibits GABA-T

A

Vigabatrin

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13
Q

Drugs that act on GABAa receptors

A

Benzo & Phenobarbital

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14
Q

MOA of tiagabine

A

Inhibits GABA reuptake by blocking GAT-1

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15
Q

MOA of vigabatrin

A

Prolongs GABA half life by blocking degradation via GABA-T

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16
Q

Hallmark of simple partial seizure

A

presevation of consciousness

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17
Q

Usual location of complex partial seizure

A

bilateral limbic system

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18
Q

Hallmark of complex partial seizure

A

automatism

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19
Q

Feature of secondarily generalized seizure

A

Amnestic

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20
Q

Length of tonic phase of GTCS

A

15-30sec

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21
Q

length of clonic phase of GTCS

A

60-120 sec

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22
Q

Seizure type with sudden onset and abrupt cessation

A

Petit mal (absence)

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23
Q

Duration of Absence seizures

A

10-45 sec

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24
Q

Age of onset of absence

A

childhood or adolesence

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25
EEG findings of absence
2.5-3.5Hz spike and wave pattern
26
Presentation of atonic seizure
sudden loss of postural tone
27
Basis of epileptic treatment
empiric seizure classification
28
When is multipple drug therapy needed?
when two or more types of seizure occur in the same patient
29
How to discontinue anti-epileptics
reduce dose gradually
30
Most common cause of failure of therapy
faulty compliance
31
N substitution of heterocyclic ring
hydantoin
32
CN substitution of heterocyclic ring
Barbiturates
33
O substitution of heterocyclic ring
Oxazolidinedione
34
C substitution of heterocyclic ring
Succinamides
35
NH2 substitution of heterocyclic ring
Acetylureas
36
Conventional drugs used for all partial seizures and GTCS
Carbamenzapine, Phenytoin, Valproate
37
Conventional drugs for Absence
Ethosuxamide, Valproate
38
Conventional drug for myoclonic seizure
Valproate
39
Structure of phenytoin
diphenolhydantoin | 2 phenols + hydantoin (N)
40
Substitution responsible for sedation
alkyl
41
Major MOA of phenytoin
block presynaptic VG Na channels in inactive state
42
reason for use dependent effect of phenytoin
preferential binding to and prolongation of inactivated state of VG Na channel
43
Presynaptic effects of phenytoin
decrease glutamate release | inscrease GABA release
44
Amount of absorption of phenytoin salt in GI tract
almost complete
45
Therapeutic levels of Phenytoin
10-20 mcg/mL
46
Oral therapy dose for adults (Phenytoin)
start at 300mg/day
47
Relationship between phenytoin dose and plasma concentrations
Non-linear (metabolism is saturable)
48
Why is Phenytoin not recommended to be given IM
drug precipitation in muscle occurs & unpredictable absorption
49
Drug interaction of Pheytoin
Enzyme INDUCER
50
Most common ADR of Phenytoin
diplopia and ataxia gingival hyperplasia and hirsutism (less common)
51
ADRs of long term use of phenytoin
Coarsening of facial features, mild peripheral neuropahty, osteomalacia
52
Prodrug of Phenytoin
Fosphenytoin
53
Advantage of Fos phenytoin over phenytoin
more soluble
54
Fosphenytoin IV indication
convulsive status epilepticus
55
DOC for convulsive status epilepticus
Fosphenytoin IV
56
Sites of accumulation of Fosphenytoin
brain, liver, muscle, and fat
57
CSF concentration of Fosphenytoin
CSF concentration proportionate to free plasma level
58
After therapeutic level of drug is attained, how will small rises in drug level affect patient's physiologic response?
toxicity symptoms due to saturation of metabolism
59
Toxicity of rapid IV push Fosphenytoin
cardiac arrhythmias
60
Moeity in carbamazepine structure
ureide
61
Indications of Carbamazepine
Trigeminal neuralgia Neuropathic pain Manic-depressive pX
62
Anti-epileptic drug used for trigeminal neuralgia
Carbamanzepine
63
AED drug similar to imipramine and other anti-depressants
Carbamazepine
64
MOA of carbamazepine
block presynaptic VG Na channels in inactive state
65
Is carbamazepine sedating?
No carbamazepine is not sedating
66
Drug interaction of Carbamanzepine
Enzyme INDUCER | can increase metabolism of Primidone, Phenytoin, Ethosuximide, Valproic Acid, Clonazepam
67
Active metabolite of carbamanzepine
Carbamazepine-10,11-epoxide
68
Therapeutic level where you may experience diplopia with carbamazepine
7mcg/mL
69
Drug interaction of Valproic Acid
Enzyme Inhibitor
70
Drug interaction of Phenobarbital
Enzyme INDUCER
71
Most common dose-related ADR of Carbamazepine
Diplopia and ataxia
72
Most common idosyncratic ADR of carbamazepine
erythematous skin rash
73
Most fatal idosyncratic ADRs of carbamazepine
blood dyscrasias, aplastic anemia, agranulocytosis within 4 months of treatment
74
Recommended action for carbamazepine toxicity
careful monitoring rather than discontinuation (unless persistent)
75
Benefit of Oxcarbazepine over carbamazepine
improved toxicity profile
76
Other dose-related ADRs of carbamazepine
mild GI upset Hyponatremia H2O intoxication
77
Metabolite of Oxcarbazepine
Eslicarbazepine both R- and S+ form (excreted as gluconoride)
78
Chirality of Eslicarbazepine
S+ enantiomer
79
Toxicity profile of oxcarbazepine
less hypersensitivity | Hyponatremia is more common
80
Indication for Eslicarbazepine Acetate (ESL)
adjunct or monotherapy for partial onset seizure
81
drug that has autoinduction (enzyme inducer of itself)
carbamazepine
82
ADR of eslicarbazepine acetate
headache, dizziness, nausea Rare: hyponatremia, hypersensitivity, suicidal ideation (stronger in carbamazepine and oxcarbazepine)
83
Drug with effect on oral contraceptives (and it's effect)
Eslicarbazepine | decreases ethinylestradiol and levonorgestrel
84
Metabolite of eslicarbazepine acetate (ESL)
Eslicarbazepine S+ only
85
Metabolite of Fospheytoin
Phenytoin
86
Most potent between carbamazepine, oxcarbazepine, and eslicarbazepine?
carbamazepine (also most ADRs)
87
Oldest non-sedative AED
Phenytoin
88
Oldest of the current AED
Phenobarbital
89
Is phenobarbital sedating?
Yes phenobarbital is sedating
90
When is phenobarbital a DOC
in infants only
91
DOC for infants
phenobarbital
92
MOA of phenobarbital (in relation to GABA)
Binds to GABAa Receptor allosterically to keep it open LONGER (increase GABA effect)
93
What type of channel is GABAa
Cl- channel
94
pH reading of phenobarbital
weak acid (therefore increased absorption when plamsa is acidic and decreased absorption if plasma is basic)
95
Mephobarbital structure
methylated phenobarbital
96
metharbital structure
methylated barbital
97
Primidone structure
2-desoxyphenobarbital
98
Metabolites of Primidone
Phenobarbital | Phenyethanolamide (PEMA)
99
MOA of Primidone
block presynaptic VG Na channels in inactive state
100
Prodrug of phenobarbital and Phenylethanolamide
Primidone
101
Most effective plasma level of Primidone
8-12mcg/mL
102
third line drug for partial seizures (refractory cases)
Felbamate
103
Indication for felbamate
third line for partial seizures (refractory) | Lennox-Gastaut syndrome
104
MOA of felbamate
use-dependent block of NMDA receptor (post synaptic Glutamate receptor) Potentiates GABA a Receptor
105
Lennox Gastaut Syndrome
epilepsy with different types of seizures (mostly tonic and atonic) usually impaired cognitive function EEG slowing and spike wave burst less than 2.5 Hz
106
Therapeutic effects of Gabapentin and Pregabalin
anti-seizure and analgesic
107
MOA of Gabapentin and Pregabalin
bind to VG Ca channels (presynaptic Glutamate) | = decrease in glutamate secretion
108
True of False Gabapentin and Pregabalin can act directly on GABA receptors
False they do not act directly on GABA receptors even if they are GABA analogs but they may act indirectly to increase GABA release
109
ADR of Gabapentin and Pregabalin
Somnolence, dizziness, headache, ataxia, tremors
110
Are Gabapentin and Pregabalin sedating?
Yes they are sedating
111
Drug interaction of Gabapentin
NO enzyme induction (negligable drug interactions)
112
Indications for Gabapentin
``` Adjunct for partial and generalized T-C seizures Monotherapy (but in high doses) Neuropathic pain (POST HERPETIC NEURALGIA) ```
113
AED for post-herpetic neuralgia
Gabapentin
114
Indications for Pregabalin
Adjunct for partial and generalized T-C seizures Neuropathic pain (POST HERPETIC NEURALGIA, DM NEUROPATHY, FIBROMYALGIA) Generalized Anxiety disorder
115
1st drug approved for Fibromyalgia
Pregabalin
116
AED that can be used for generalized anxiety disorder
Pregabalin
117
MOA of Lacosamide
enhances SLOW inactivation of presynaptic glutamate VG Na channels (other AEDs prolong FAST inactivation) Binds to presynaptic glutamate CRMP-2
118
Chirality of Lacosamide
R(+) enantiomer
119
indication fro Lacosamide
adjunct for patial seizures (w/ or w/o secondary generalization)
120
Age to prescribe Lacosamide
>16y/o
121
ADRs of Lacosamide
Dizziness, headache, Nausea, Diplopia
122
Drug interaction of Lacosamide
NO induction/inhibition of enzymes (negligable drug interaction)
123
MOA of Lamotrigine
Blockage of presynaptic glutamate VG Na channels | Inhibit presynaptic glutamate Ca channels
124
Indication of Lamotrigine
Monotherapy: Partial seizures, Absence, myoclonic seizures, Lennox-Gastaut Bipolar Disorder
125
AED used for Bipolar disorder
Lamotrigine
126
ADRs of Lamotrigine
Somnolence, dizziness, headache, Nausea, Diplopia
127
Is lamotrigine sedating?
Yes it is sedating
128
MOA of Levetiracem
binds selectively to the synaptic vesicular protein SV2A`
129
Drug interaction of Levitiracem
NO induction/inhibition of enzymes (negligable drug interaction)
130
Indication of Levetiracem
Adult: Partial seizure Children: Primary GTCS and Juvenile Myoclonic seizure
131
ADRs of Levetiracem
Somnolence, Dizziness, Ataxia, ASTHENIA
132
Is levetiracem sedating
Yes it is
133
MOA of Retigabine or Ezogabine
K channel facilitator via KCNQ gene
134
Retigabine Indication
Partial seizure in adults
135
ADRs of Retigabine
Somnolence, dizziness, confusion, blurred vision, DYSARTHRIA
136
MOA of Tiagabine
inhibit GABA reuptake via GAT-1 inhibition
137
Tiagabine indication
Primary GTCS
138
ADRs of Tiagabine
Nervousness, dizziness, difficulty concentrating, DEPRESSION, tremor
139
MOA of topimarate
blockade of VG Na channels | Blocks postsynaptic glutamate AMPA receptors
140
Topimarate indication
Monotherapy: partial and genralized T-C seizure, Lennox Gastaut Seizure
141
ADRs of Topimarate
Somnolence, dizziness cognitive slowing, nervousnessm fatigue, paresthesias
142
MOA of Vigabatrin
Irreversibly inhibits GABA-T = inhibited degradation of GABA
143
Effect of Vigabatrin of GABAa Receptors
Desensitization due to increased GABA levels and prolonged activation
144
Indication of Vigabatrin
Partial seizures and infantile spasms
145
Which is the active enantiomer of vigabatrin
S+
146
ADRs of Vigabatrin
WEIGHT GAIN, drowsiness, dizziness, peripheral visual field defects
147
Structural substitution of ethosuxamide
Succinamide (C)
148
Indication of ethosuxamide
pure petit mal drug
149
Most commonly used petit mal drug
Ethosuxamide
150
Compare Phensuxamide and Metgsuxamide with ethosuxamide
Phensuxamide: less effective Methsuxamide: more toxic
151
MOA of ethosixamide
Effect on presynaptic glutamate Ca channels | Reduce low threshold T-Type Ca current in thalamic neurons
152
3 drugs for Absence seizure
Ethosuxamide & Valproate > Lamotrigine
153
Structure of Valproic Acid and Sodium Valproate
Fatty carboxylic Acid
154
Active form of Valproic Acid and Sodium Valproate
Valproate
155
at what pH is valproic acid fully ionized
body pH (therefore it turns into active form in the body -- valproate)
156
MOA of Valproate
Blocks Na currents Block NMDA receptor mediated excitation Inhibit GAT-1 (reuptake) Facilitate glutamic acid decarboxylase (GABA synthesis)
157
Indications of Valproate
BROADD Preferred in absence over ethosux only if with concomitant GTCS Myoclonic seizure (unique and very dramatic) Bipolar Disorder Migraine Prophylaxis
158
AED effective for migrane prophylaxis
Valproate
159
Drug interaction of Valproate with phenytoin
Valproate + Phenytoin = displace phenytoin from plasma proteins
160
ADRs of Valproate
``` GIT disturbance (common dose-related) Fine tremors (high levels) WEIGHT GAIN, hair loss (uncommon) Hepatotoxicity (Idiosyncratic) TERATOGENIC (Spina bifida, CVS, orofacial, digital deformities) ```
161
Trimethadione structural substitution
oxazolidinedione
162
Indication of thrimethadione
PREVIOUS DOC for absence (replaced by ethosuxamide)
163
active metabolite of themethadione
dimethadione
164
MOA of trimethadione
raises threshold for seizure discharge after repetitive thalamic stimulation (Ca current)
165
How do you supress absence seizures?
inhibiting pacemaker action of thalamic neurons (Ca current)
166
ADRs of Trimethadione
Sedation | CI w/ pregnancy
167
Indication of Diazepam
DOC for status epilepticus (IV)
168
Limit of Diazepam use for seizure control
tolerance develops to oral meds (not useful for long term) and sedation
169
Indication of Lorazepam
Status epilepticus IV
170
Lorazepam benefits over Diazepam
more effective and longer acting then diazepam | Easier to administer in IV (water based)
171
Indication for Clonazepam
Absence Myoclonic seizure Infantile spasms (long acting and very potent)
172
Indication for Nitrazepam
Myoclonic seizure | Infantile spasm
173
Indication for clorazepate dipotassium
Adjunct for complex partial seizure in adults
174
Less sedating benzodiazepam
clobazam
175
Active metabolite of clobazam
norclobazam
176
MOA of Acetazolamide
carbonic acid anhydrase inhibitor | Depolarizing effect of bicarbonate ions in neurons via GABA R ion channes may be diminished
177
Limiting factor to Acetazolamide use
Tolerance
178
Indication for Acetazolamide use
women with seizure exacerbation during menstruation
179
DOC for inflantile spasms
Vigabatrin
180
Drugs that work on infantile spasms
IM corticotropin or oral prednisone Benzos (clonazepam or nitrazepam) Vigabatrin (DOC)
181
Most common status epilepticus
GT-T status epilepticus
182
Definitive therapy for statue epilepticus
phenytoin | Phenobarbital (if refractory to phenytoin)
183
teratogenic effect of Phenytoin
fetal hydantoin syndrome | cleft lip/palate, congenital heart disease, slowed growth, mental deficiency
184
Teratogenic effects of Valproate
Spina Bifida
185
Drugs that are most difficult to discontinue
barbiturates and benzodiazepams (weeks-months)
186
When do you try to discontinue drugs?
when patient has been seizure free for 3-4 years
187
Most dangerous effect of AED
respiratory depression (potentiated by alcohol)
188
Treatment for overdose
supportive do not use stimulants ALKALINIZE URINE
189
3 drugs that can be used for all types of seizures
valproate, topiramate, lamotrigine

Pharmacology (2 decks)

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