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Neuroscience > Neuroscience Week 6: Anticonvulsants > Flashcards

Neuroscience Week 6: Anticonvulsants Flashcards

1
Q

Objectives

A
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2
Q

Classification of seizures

A
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3
Q

Classic Anticonvulsant drugs

6 listed

A
  • Phenobarbital
  • Phenytoin
  • Ethosuximide
  • Diazepam
  • Valproic acid
  • Carbamazepine
    *
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4
Q

Newer Anticonvulsant drugs

8 listed

A
  • Lamotrigine
  • Gabapentin
  • Topiramate
  • Tiagabine
  • Levetiracetam
  • Oxycarbazepine
  • Vigabatrin
  • Fosphenytoin
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5
Q

Classic Anticonvulsant drugs prototypes

5 listed

A
  • Phenytoin
  • Ethosuximide
  • Diazepam
  • Valproic acid
  • Carbamazepine
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6
Q

Newer Anticonvulsant drugs prototypes

A
  • Lamotrigine
  • Oxcarbazepine
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7
Q

The “Treatable Epilepsies”: Simple Partial seizures

A

~25%

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8
Q

The “Treatable Epilepsies”:complex partial seizures

A

40-50%

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9
Q

The “Treatable Epilepsies”: Tonic clonic seizures

A

~25%

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10
Q

The “Treatable Epilepsies”: Absence seizures

A

<10%

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11
Q

Simple seizure location

A
  • elementary
  • cortical
  • focal
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12
Q

Complex seizures location

A
  • Temporal lobe
  • limbic
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13
Q

The “Treatable Epilepsies”: overview

A
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14
Q

Generalized absence epilepsy: Circuit elements

3 listed

A
  1. Glutamatergic cortical pyramidal neuron
  2. Glutamatergic ventrobasal thalamo-cortical neuron
  3. GABAergic thalamic reticular neuron
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15
Q

Generalized absence epilepsy: Circuit

A
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16
Q

Identify EEG

A
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17
Q

Fill in table

A
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18
Q

Ethosuximide: Inhibit T-Type VSCaCs

A

Yes

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19
Q

Valproate: Inhibit T-Type VSCaCs

A

Yes

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20
Q

Carbamazepine: Inhibit T-Type VSCaCs

A

No

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21
Q

Phenytoin: Inhibit T-Type VSCaCs

A

No

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22
Q

Ethosuximide: Treat Generalized Absence seizures

A

Yes

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23
Q

Valproate: Treat Generalized Absence seizures

A

Yes

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24
Q

Carbamazepine: Treat Generalized Absence seizures

A

No

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25
Q

Phenytoin: Treat Generalized Absence seizures

A

No

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26
Q

Anticonvulsant effects on action potentials vs burst firing

A
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27
Q

voltage-sensitive Na channels AKA

A

VSNaCs

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28
Q

Stages of voltage-sensitive Na channels

A
  • Resting
  • Activated
  • Inactivated
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29
Q

Fill in table

A
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30
Q

Ethosuximide: Use-dependent inhibition of VSNaCs

A

No

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31
Q

Valproate: Use-dependent inhibition of VSNaCs

A

Yes

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32
Q

Carbamazepine: Use-dependent inhibition of VSNaCs

A

Yes

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33
Q

Phenytoin: Use-dependent inhibition of VSNaCs

A

Yes

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34
Q

Ethosuximide: Treat Simple partial Sz, Complex partial Sz and Generalized Tonic-Clonic

A

No

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35
Q

Valproate: Treat Simple partial Sz, Complex partial Sz and Generalized Tonic-Clonic

A

Yes

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36
Q

Carbamazepine: Treat Simple partial Sz, Complex partial Sz and Generalized Tonic-Clonic

A

Yes

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37
Q

Phenytoin: Treat Simple partial Sz, Complex partial Sz and Generalized Tonic-Clonic

A

Yes

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38
Q

Fill in table

A
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39
Q

Phenytoin: Treat Partial Seizures

A

Yes

1st line or preferred

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40
Q

1st line or preferred treatment of partial seizures

A

Phenytoin

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41
Q

Fosphenytoin: Treat Partial Seizures

A

Yes

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42
Q

Carbamazepine: Treat Partial Seizures

A

yes

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43
Q

Oxycarbazepine: Treat Partial Seizures

A

Yes

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44
Q

Levetiracetam: Treat Partial Seizures

A

Yes

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45
Q

Topiramate: Treat Partial Seizures

A

Yes

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46
Q

Phenobarbital: Treat Partial Seizures

A

Yes

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47
Q

Tigabine: Treat Partial Seizures

A

Yes

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48
Q

Gabapentin: Treat Partial Seizures

A

Yes

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49
Q

Valproic acid: Treat Partial Seizures

A

Yes

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50
Q

Lamotrigine: Treat Partial Seizures

A

Yes

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51
Q

Ethosuximide: Treat Partial Seizures

A

No

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52
Q

Benzodiazepines: Treat Partial Seizures

A

No

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53
Q

Diazepam: Treat Partial Seizures

A

No

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54
Q

Phenytoin: Treat Generalized Tonic-Clonic Seizures

A

Yes

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55
Q

Carbamazepine: Treat Generalized Tonic-Clonic Seizures

A

Yes

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56
Q

Oxycarbazepine: Treat Generalized Tonic-Clonic Seizures

A

Yes

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57
Q

Levetiracetam: Treat Generalized Tonic-Clonic Seizures

A

Yes

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58
Q

Topiramate: Treat Generalized Tonic-Clonic Seizures

A

Yes

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59
Q

Phenobarbital: Treat Generalized Tonic-Clonic Seizures

A

Yes

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60
Q

Tiagabine: Treat Generalized Tonic-Clonic Seizures

A

No

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61
Q

Gabapentin: Treat Generalized Tonic-Clonic Seizures

A

No

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62
Q

Valproic acid: Treat Generalized Tonic-Clonic Seizures

A

Yes

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63
Q

Lamotrigine: Treat Generalized Tonic-Clonic Seizures

A

Yes

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64
Q

Ethosuximide: Treat Generalized Tonic-Clonic Seizures

A

No

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65
Q

Benzodiazepines: Treat Generalized Tonic-Clonic Seizures

A

No

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66
Q

Diazepam: Treat Generalized Tonic-Clonic Seizures

A

No

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67
Q

Phenytoin: Treat Absence Seizures

A

No

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68
Q

Fosphenytoin: Treat Absence Seizures

A

No

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69
Q

Carbamazepine: Treat Absence Seizures

A

No

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70
Q

Oxcarbazepine: Treat Absence Seizures

A

No

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71
Q

Levetiracetam: Treat Absence Seizures

A

No

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72
Q

Topiramate: Treat Absence Seizures

A

No

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73
Q

Phenobarbital: Treat Absence Seizures

A

No

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74
Q

Tiagabine: Treat Absence Seizures

A

No

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75
Q

Gabapentin: Treat Absence Seizures

A

No

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76
Q

Valproic acid: Treat Absence Seizures

A

Yes

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77
Q

Lamotrigine: Treat Absence Seizures

A

Yes

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78
Q

Ethosuximide: Treat Absence Seizures

A

Yes

1st line or preferred

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79
Q

1st line or preferred treatment of Absence Seizures

A

Ethosuximide

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80
Q

Benzodiazepines: Treat Absence Seizures

A

No

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81
Q

Diazepam: Treat Absence Seizures

A

No

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82
Q

Phenytoin: Treat Status Epilepticus

A

Yes

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83
Q

Fosphenytoin: Treat Status Epilepticus

A

Yes

1st line or preferred

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84
Q

Carbamazepine: Treat Status Epilepticus

A

No

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85
Q

Oxcarbazepine: Treat Status Epilepticus

A

No

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86
Q

Levetiracetam: Treat Status Epilepticus

A

No

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87
Q

Topiramate: Treat Status Epilepticus

A

No

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88
Q

Phenobarbital: Treat Status Epilepticus

A

Yes

89
Q

Tiagabine: Treat Status Epilepticus

A

no

90
Q

Gabapentin: Treat Status Epilepticus

A

No

91
Q

Valproic Acid: Treat Status Epilepticus

A

No

92
Q

Lamotrigine: Treat Status Epilepticus

A

No

93
Q

Ethosuximide: Treat Status Epilepticus

A

No

94
Q

Status Epilepticus 1st line or preferred treatment

A

fosphenytoin

95
Q

Benzodiazepines: Treat Status Epilepticus

A

No

96
Q

Diazepam: Treat Status Epilepticus

A

Yes

97
Q

Phenytoin: blocks VSNaCs

A

Yes

98
Q

Forphenytoin: blocks VSNaCs

A

Yes

99
Q

Carbamazepine: blocks VSNaCs

A

Yes

100
Q

Oxcarbazepine: blocks VSNaCs

A

Yes

101
Q

Levetiracetam: blocks VSNaCs

A

Yes

102
Q

Topiramate: blocks VSNaCs

A

Yes

103
Q

Phenobarbital: blocks VSNaCs

A

Yes

104
Q

Tiagabine: blocks VSNaCs

A

Yes

105
Q

Gabapentin: blocks VSNaCs

A

Yes

106
Q

Valproic acid: blocks VSNaCs

A

Yes

107
Q

Lamotrigine: blocks VSNaCs

A

Yes

108
Q

Ethosuximide: blocks VSNaCs

A

No

109
Q

Benzodiazepines: blocks VSNaCs

A

Yes

110
Q

Diazepam: blocks VSNaCs

A

No

111
Q

Phenytoin: blocks T-type VSCaCss

A

No

112
Q

Fosphenytoin: blocks T-type VSCaCss

A

No

113
Q

Carbamazepine: blocks T-type VSCaCss

A

No

114
Q

Oxcarbazepine: blocks T-type VSCaCss

A

No

115
Q

Levetiracetam: blocks T-type VSCaCss

A

No

116
Q

Topiramate: blocks T-type VSCaCss

A

No

117
Q

Phenobarbital: blocks T-type VSCaCss

A

No

118
Q

Tiagabine: blocks T-type VSCaCss

A

No

119
Q

Gabapentin: blocks T-type VSCaCss

A

No

120
Q

Valproic acid: blocks T-type VSCaCss

A

Yes

121
Q

Lamotrigine: blocks T-type VSCaCss

A

Yes

122
Q

Ethosuximide: blocks T-type VSCaCss

A

Yes

123
Q

Benzodiazepines: blocks T-type VSCaCss

A

No

124
Q

Diazepam: blocks T-type VSCaCss

A

No

125
Q

Phenytoin: Other actions

A

None

126
Q

Fosphenytoin: Other actions

A

None

127
Q

Carbamazepine: Other actions

A

Muscarinic antagonist

128
Q

Oxcarbazepine: Other actions

A

None

129
Q

Levetiracetam: Other actions

A

Modulate Glu & GABA release?

130
Q

Topiramate: Other actions

A

↑ GABA action

131
Q

Phenobarbital: Other actions

A

↑ GABA-A action (weak)

132
Q

Tiagabine: Other actions

A

GABA reuptake inhibitor

133
Q

Gabapentin: Other actions

A

↓ “high voltage-gated” Ca2+ channels

134
Q

Valproic acid: Other actions

A

GABA transaminase inhibitor

135
Q

Lamotrigine: Other actions

A

Inhibits glutamate release

136
Q

Ethosuximide: Other actions

A

None

137
Q

Benzodiazepines: Other actions

A

GABA-A positive allostermeric modulator

138
Q

Diazepine: Other actions

A

None

139
Q

Putative sites of anticonvulsant action

2 listed

A
  • T-type Voltage-sensitive Ca2+ channel inhibition (VSCACs)
  • “use-dependent” inhibition of voltage sensitive Na+ channels (VSNaCs)
140
Q

Abosorption of anticonvulsants

A

Variable absorption among patients

141
Q

Anticonvulsants plasma binding and exception

A

High degree of plasma protein binding (75-95%)

except Ethosuximide and more variable with newer drugs

142
Q

Anticonvulsants drug interactions

A

interfere with metabolism of other drugs

143
Q

Anticonvulsants metabolism

A

Induction of self-metabolism & other drug metabolisms

(Most notably with phenytoin, carbamazepine and phenobarbital)

144
Q

Anticonvulsants Non-linear dose

A

Plasma concentration curves

(most notable for phenytoin and phenobarbital)

145
Q

Consequences of anticonvulsant overdose

A
  • Most serious effect is respiratory depression
  • Management of overdose is largely by supportive measures to sustain cardiovascular and respiratory function
  • Rarely fatal, unless another CNS depressant is present (ethanol or benzodiazepines)
  • Becoming a growing concern with increased use for other indications
146
Q

Most common side effects of anticonvulsants

A
  • GI distress, nausea and vomiting
  • sedation, dizziness, ataxia and diplopia
  • Cognitive slowing / impairments (dose-dependent)
  • There is a variable degree of expression of side effects in patients
  • Some tolerance may develop with repeated administration
147
Q

More serious side effects of anticonvulsants categories

3 listed

A
  • Hematologic
  • Hepatic
  • Dermatologic
148
Q

More serious side effects of anticonvulsants: Hematologic

A
  • aplastic anemia
  • Thrombocytopenia
  • Lupus-like syndrome
  • Agranulocytosis
149
Q

More serious side effects of anticonvulsants: Hepatic

A

Hepatic Failure

Fulminating necrosis (pediatric & elderly patients)

150
Q

More serious side effects of anticonvulsants: Dermatologic

A
  • Steven-Johnson Syndrome
  • Toxic Epidermal Necrolysis
151
Q

Fill in table

A
152
Q

Ethosuximide Side Effects: GI

A
  • Distress
  • Nausea
  • Vomiting
153
Q

Ethosuximide Side Effects: Neurologic

A
  • Headache
  • Fatigue
154
Q

Ethosuximide Side Effects: Dermatologic

A
  • Itching
  • Steven-Johnson syndrome
155
Q

Valproate Side Effects: GI

A
  • Distress
  • Nausea
  • Vomiting
156
Q

Valproate Side Effects: Neurologic

A

Tremor

157
Q

Valproate Side Effects: Metabolic

A

Weight gain

Pancreatitis

Hepatotoxicity (rare but serious)

158
Q

Valproate side effect that is rare but can be serious

A

Hepatotoxicity

159
Q

Valproate Side Effects: reproductive

A

Teratogenic potential

160
Q

Phenytoin Side Effects: GI

A
  • Distress
  • Nausea
  • Vomiting
161
Q

Phenytoin Side Effects: Neurologic

A
  • Nystagmus
  • diplopia
  • ataxia
  • sedation
  • peripheral neuropathy
162
Q

Phenytoin Side Effects: Dermatologic

A
  • Hirsutism
  • gingival hyperplasia
  • Steven-Johnson Syndrome
163
Q

Phenytoin Side Effects: Hematologic

A

Megaloblastic anemia

164
Q

Phenytoin Side Effects: Reproductive

A

Teratogenic potential

165
Q

Phenytoin Side Effects: Musculoskeletal

A
  • Osteopenia
  • Lupus-like Syndrome
166
Q

Carbamazepine Side Effects: GI

A
  • Distress
  • nausea
  • vomiting
167
Q

Carbamazepine Side Effects: Neurologic

A
  • diplopia
  • ataxia
168
Q

Carbamazepine Side Effects: Dermatologic

A

Steven-Johnson Syndrome

169
Q

Carbamazepine Side Effects: Hematologic

A
  • Agranulocytosis
  • aplastic anemia
170
Q

Carbamazepine Side Effects: Reproductive

A

Teratogenic potential

171
Q

Carbamazepine Side Effects: Cardiovascular

A
  • Tachycardia
  • arrhythmias
172
Q

Teratogenic consequences of anticonvulsants

A
  • Fetal Hydantoin Syndrome (Phenytoin, Phenobarbital and Carbamazepine)
  • Spina bifida (valproate)
  • 2 fold increased risk of congenital malformations
  • 3 fold increased risk of autism with valproate
  • Risk increases with combinations of anticonvulsants
  • Consensus is to minimize exposure to anticonvulsants while not allowing maternal seizures to go unchecked
173
Q

Fetal Hydantoin Syndrome similar phenotype to?

A

Fetal Alcohol Syndrome (FAS)

174
Q

Fetal Hydantoin Syndrome phenotype

A
  • Small eyes
  • smooth philtrum
  • thin upper lip
  • Wide flat nasal bridge
  • smaller head circumference
175
Q

Spina Bifida Phenotype

A

Incomplete closure of the neural tube

176
Q

Anticonvulsants that can lead to Fetal Hydantoin Syndrome

A
  • Phenytoin
  • Phenobarbital
  • Carbamazepine
177
Q

Anticonvulsants that can lead to Spina Bifida

A

Valproate

178
Q

Anticonvulsants that can lead to autism

A

3 fold increased risk with valproate

179
Q

Therapeutic goals for newer anticonvulsant drugs

A
180
Q

Oxcarbazepine similar structure to?

A

Carbamazepine

181
Q

Oxcarbazepine Action

A

VSNaCs

182
Q

Oxcarbazepine Plasma protein binding

A

40%

183
Q

Oxcarbazepine Advantages

A

↓ Incidence of drug interactions

↓ affinity as muscarinic antagonist

184
Q

Oxcarbazepine concerns

A

Other side effects similar to carbamazepine

185
Q

Oxcarbazepine Clinical uses

A

Monotherapy for:

  • Partial seizures
  • generalized tonic-clonic
186
Q

Carbamazepine and Oxcarbazepine metabolism

A
187
Q

Oxcarbazepine Overview

A
188
Q

Lamotrigine Structure

A

similar to Phenytoin

189
Q

Lamotrigine action

A

VSNaCs & VSCaCs (presynaptic)

190
Q

Lamotrigine plasma protein binding

A

55%

191
Q

Lamotrigine advantages

A
  • ↓ cognitive side effects
  • Less teratogenic potential
192
Q

Lamotrigine concerns

A
  • Other Phenytoin-like side effects
  • Dermatologic syndromes
  • Hepatotoxicity
193
Q

Lamotrigine Clinical uses

A

Monotherapy for:

  • Partial seizures
  • Generalized Tonic-Clonic seizures
  • some efficacy for General Absence seizures
194
Q

Lamotrigine Overview

A
195
Q

Levetiracetam Structure

A

Piracetam analog

196
Q

Levetiracetam action

A

VSNaCs & VSCaCs (presynaptic)

197
Q

Levetiracetam Plasma protein binding

A

< 10%

198
Q

Levetiracetam Concerns

A
  • Somnolence
  • dizziness
  • ataxia
  • irritability
  • aggression
  • anxiety
199
Q

Levetiracetam advantages

A

minimal drug interactions?

200
Q

Levetiracetam Clinical uses

A

Monotherapy or combination therapy for:

  • Partial seizures
  • Generalized Tonic-clonic
201
Q

Principles of Anticonvulsant therapy I

A
202
Q

Principles of Anticonvulsant therapy II

A
203
Q

Relative degree of successful response to anticonvulsant therapy: Absence seizures

A

Good

204
Q

Relative degree of successful response to anticonvulsant therapy: Tonic-clonic

A

adequate

205
Q

Relative degree of successful response to anticonvulsant therapy: Simple partial

A

Adequate

206
Q

Relative degree of successful response to anticonvulsant therapy: Complex partial

A

Fair-Poor

207
Q

Relative degree of successful response to anticonvulsant therapy: Others (newborn, infancy, early childhood)

A

Poor

208
Q

Refractory to anticonvulsants Surgical treatments for seizures

2 listed

A
  • surgical resection
  • Vagus nerve stimulator
209
Q

Refractory to anticonvulsants Surgical treatments for seizures: Surgical Resection

A
  • Often temporal lobe in origin
  • Efforts to limit resection area by EEG / MEG & MRI
  • Postoperative anticonvulsant medication required
210
Q

Refractory to anticonvulsants Surgical treatments for seizures: Vagus Nerve Stimulator

A
  • Adjunct treatment for focal seizures
  • Seizure repression mechanism uncertain
  • Patient activated at onset of seizure
  • Efficacy appears to increase over time
211
Q

Status epilepticus concerns

A

Neurological emergency!

  • Seizures lasting more than 5 minutes
  • Neurological damage at ~ 30 minutes
212
Q

Status epilepticus Treatment

A
  • Diazepam, Lorazepam and Fos-Phenytoin IV (efficacious in 2/3 of patients)
  • Inhalation Anesthetics
213
Q

Other uses of anticonvulsants

4 listed

A
  • Bipolar disorder
  • Trigeminal Neuralgia
  • Neuropathic pain / Diabetic neuropathy
  • Migraine
214
Q

Anticonvulsants for bipolar disorder

A
  • Carbamazepine
  • Valproate
  • Lamotrigine
  • Oxcarbazepine
215
Q

Anticonvulsants for Trigeminal Neuralgia

A
  • Carbamazepine
  • Oxcarbazepine
216
Q

Anticonvulsants for Neuropathic pain

A
  • Gabapentin
  • Pregabalin
217
Q

Anticonvulsants for Diabetic Neuropathy

A
  • Gabapentin
  • Pregablin
218
Q

Anticonvulsants for Migraine

A
  • Valproate
  • Topiramate
219
Q

status epilepticus drugs are

3 listed

A

fosphenytoin, phenobarbital, diazepam

Neuroscience (96 decks)

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