Anti-Seizure Drugs Flashcards
1
Q
What is the difference between epilepsy & seizures? Describe the differences.
A
difference = duration of symptoms
Epilepsy: chronic, recurrent
Seizures: Finite, resolves
2
Q
A transient disturbance of cerebral function due to an abnormal paroxysmal neuronal discharge in the brain.
What is this?
A
Seizure
3
Q
Which drugs lower seizure threshold?
A
- theophylline
- alcohol
- high dose phenothiazines (anti-psychotics)
- antidepressants (esp bupropion)
- street drugs
4
Q
What is the goal of treatment with anti-seizure medication?
A
- eliminate symptoms (seizures) with minimal side effects
- complete seizure freedom
5
Q
______-_____% of pts may not be free from seizures and seizure control must be balanced with ___goals
A
20-35
QOL
6
Q
When do we initiate therapy?
A
- no risk factors, normal MRI, normal EEG
- if risk factors present
- pts who have had 2 or more unprovoked seizures
7
Q
Probability of a second seizure is less than 10% in the first year and approximately 21% by the end of 2 years
This is true for what type of pts?
A
pts with no risk factors, normal MRI, normal EEG
8
Q
It is critical to establish an accurate diagnosis of the _________ and ________
A
seizure type
epilepsy classification
9
Q
It is estimated that up to ____% of patients with epilepsy are nonadherent to medication.
A
60
10
Q
T/F: Monotherapy is preferred for pts with seizures.
A
TRUE
11
Q
When should you consider stopping pt on meds?
A
Factors favoring successful withdrawal of ADS:
- seizure free period of 2-4 years
- complete seizure control within 1 year of onset
- onset of seizures between 2-35y/o
AND
normal neurologic examination and EEG
12
Q
What are the 3 mechanisms of action of ASD?
A
- Modifies ionic conductance (Na+, Ca++, K+)
- dimunition of glutamatergic transmission ( dec excitatory)
- Enhancement of GABAergic transmission (inc inhibitory)
13
Q
Glutamate is a ______ transmission
A
excitatory
14
Q
GABA is a ______ transmission
A
inhibitory
15
Q
The ultimate effect is to inhibit the local generation of seizure discharges by what 2 mechanisms?
A
- Reduce ability of neurons to fire action potentials at high rate
- reduce neuronal synchronization
16
Q
Which drugs diminish glutamate release at the presynaptic cleft?
A
- Phenytoin
- fosphenytoin
- carbamazepine
- oxcarbazepine
- eslicabazepine acetate
- lamotrigine
- lacosamide
- ethosuximide
- retigabine
- levetiracetam
- brivaracetam
- gabapentin
- gabapentin enacarbil
- pregabalin
- perampanel
- valproate
- felbamate
- adrenocorticotropin
POSSIBLY
- topiramate
- zonisamide
- rufinamide
17
Q
Which drugs act on the voltage gated Na+ channels at the presynaptic cleft?
A
- phenytoin
- carbamazepine
- lamotrigine
- lacosamide
POSSIBLY
- topiramate
- zonisamide
- rufinamide
18
Q
Which drug acts on the voltage gated Ca++ channels (T-type) at the presynaptic cleft?
A
ethosuximide
19
Q
Which drug acts on the voltage gated K+ channels at the presynaptic cleft?
A
Retigabine (ezogabine)
20
Q
Which drug inhibits the release of glutamate by binding to SV2A?
A
Levetiracetam
21
Q
Which drugs inhibit the release of glutamate by binding to the a2S subunit of P/Q type Ca++ channel?
A
gabapentin, pregabalin
22
Q
Which drug targets the post-synaptic ionotropic glutamate receptor AMPA?
A
PerAMPAnel
Perampanel
23
Q
What drugs with a mixed/unknown MOA target the post-synaptic receptors?
A
- Valproate
- felbamate
- topiramate
- zonisamide
- rufinamide
- adrenocorticotropin
24
Q
Which drugs enhance GABA inhibition?
A
- Phenobarbital
- primidone
- benzodiazapines (diazepam, lorazepam, clonazepam)
- tiagabine
- vigabatrine
POSSIBLY
- topiramate
- felbamate
- ezogabine
25
Which drugs **enhance GABA** by working on the **GABAa receptor**?
* phenobarbital
* primidone
* benzodiazipines
POSSIBLY
* topiramate
* felbamate
* ezogabine
26
Which drug **enhances GABA** by working on **(blocking)** the **GAT-1 GABA transporter**?
Tiagabine
27
Which drug **enhances GABA** by working on **(blocking)** **GABA transaminase**?
Vigabatrin
28
When **GABA** interacts at two sites between **alpha and beta subunits**, what **channel** does it trigger?
Triggers **chloride channel** opening
29
Between what sites do **benzos** bind at?
between **alpha** and **gamma** subunits
30
When benzos bind at a single site between alpha and gamma subunits, this facilitates the opening of the \_\_\_\_\_\_\_\_\_\_\_\_\_.
Which benzos specifically?
**chloride ion channel**
**Diazepam, Lorazepam**
31
\_\_\_\_\_\_\_\_\_\_ is a **benzo antagonist**
flumazenil
32
Binding sites of benzos are distinct from those of the \_\_\_\_\_\_\_\_
**barbituates**
33
What **3 drugs** can treat a newly diagnosed **generalized absence**?
* **etho**suximide
* **lamo**trigine
* **val**proic acid
34
What drugs can be used as **alternatives for refractive absence**?
* clonazepam
* topiramate
35
**T/F:** gabapentin is ineffective for new diagnosed generalized absence
TRUE
36
Ethosuximide **MOA**
blocks voltage gated **Ca++ channels (T-type)**
decreases **glutamate**
37
**Clinical Application** of Ethosuximide
Generalized absence
38
**P-kinetics and interactions** of Ethosuximide
long half-life
39
**ADE** of Ethosuximide
**Headache**
**Blood dyscrasias**
GI distress
HA
Ataxia
Drowsiness
Rash
**Chronic: behavior changes**
40
Lamotrigine **MOA**
Blocks voltage gated **Na+ channels**
decreases **glutamate**
41
Lamotrigine **Clinical applications**
generalized **absence**
generalized **tonic-clonic**
**focal aware/impare**
focal or generalized **myoclonic**
42
**Lamotrigine** has many \_\_\_\_\_\_
drug interactions
43
Lamotrigine **ADEs**
**\*\*Box warning: serious skin rash- start low & go slow**
**\*\*Diplopia**
HA
dizziness
hemophagocytic lymphohistiocytosis **(HLH)**
44
Valproate/ Valproic Acid **MOA**
**_mixed/unknown_**
increased GABA
or
enhances GABA action
or
mimics at post synaptic receptors
45
Valproate/Valproic Acid Clinical Applications
**generalized tonic-clonic**
generalized **absence**
**focal aware/impaired**
**focal/generalized myoclonic**
46
Valproate/Valproic Acid **ADEs**
**hepatotoxicity**, **teratogenic,** **pancreatitis**, **alopecia**
47
Clonazepam **MOA**
enhance GABA-A receptor responses
48
Clonazepam **clinical applications**
generalized absence
focal/generalized myoclonic
infantile spasms
49
Clonazepam **P-kinetics/ interactions**
\>80% availability
50
Clonazepam **ADEs**
sedation
51
**Topiramate MOA**
mixed/unknown
AMPA receptor inhibitor
possibly blocks VG-Na+
enhances GABA activity
52
Topiramate **Clinical Applications**
generalized absence
generalized tonic-clonic
focal aware/impaired
**migraine**
53
Topiramate P-kinetics/interactions
both **hepatic and renal clearance**
54
Topiramate **ADEs**
**Cognitive slowing**
**confusion**
sleepiness, GI sx, **metabolic acidosis,** pregnancy cat D
55
Which 4 drugs do you want to **avoid in tx of absence seizures**?
**carba**mezapine
**viga**batrin
**gaba**pentin
**tiaga**bine
56
What 2 meds are **ineffective in tx of absence seizures**?
**Phen**ytoin
**Phen**obarbital
57
What are the 4 FDA approved meds to **treat tonic-clonic seizure**s?
Lamotrigine
Levatriacetam
Perampanel
Topiramate
"The **FDA Lam**a **Leve**tated **Per Tob**y's request"
58
What happens during the **tonic phase** of the generalized tonic-clonic seizure?
* **epileptic cry**
* **cyanosis**
* **incontinence**
* generalized **stiffening** of body and lumbs, **back arched**
59
What happens during the **Clonic phase** of the generalized tonic-clonic seizure?
* **salivary frothing**
* cyanosis
* **eyes blinking**
* **clonic jerks of limbs, body and head**
60
What takes place during the **post-ictal confusional fatigue phase?**
limbs and body limp
61
* **LOC/fainting** 30 sec- 5 min
* general **muscle contraction and rigidity** 15-20 sec
* violent **rhythmic muscle contraction** and relaxation
* biting the **cheek/tongue**, **clenched teeth/jaw**
* **incontinence**
* stopped breathingor difficulty breathing during seizure
* **cyanosis**
What kind of seizure does this describe?
**Generalized tonic-clonic seizure**
62
What was given **historically** to pts who experienced generalized c-t seizures?
Phenytoin
carbamezapine
phenobarbital
valproid acid
63
Levetiracetam **MOA**
**Blocks** synaptic release machinery **(SV2A)**
## Footnote
**decreases glutamate**
64
Levetiracetam **Clinical app**
generalized t-c
focal aware/impaired
65
Levetiracetam has minimal drug interactions
## Footnote
**T/F?**
True
66
Levetiracetam ADEs
**Behavioral problems**
**HA**
sedation
seizures-focal onset
weakness
67
Carbamezapine **MOA**
Blocks V-G Na+ channels
decreases glutamate
68
Carbamezapine Clinical applications
generalized tonic-clonic
focal aware/imparied
69
Carbamezapine P-kin and interactions
many drug interactions
## Footnote
**induces own metabolism**
70
Carbamezapine ADEs
_**\*\*\*Box warning:**_ serious derm rxns & **HLA-B\* 1502 allele** (TEN; SJS) in **Asians**
## Footnote
**Aplastic anemia & agranulocytosis**
**Ataxia**
**Diplopia**
**Hyponatremia**
**Metabolic Bone Disease (MBD) (Vit D and Ca++)**
71
What is an **alt to carbamezapine** that you can use for **focal onset seizures**?
What is **diff** about this drug?
**Oxcarbazepine**
shorter 1/2 life
active metabolite
longer duration
fewer interactions reported
72
Lacosamide MOA
Blocks voltage gated Na+ channels
dec glutamate
73
Lacosamide Clinicall applications
Generalized t-c seizures
focal aware/impaired
74
Lacosamide ADE
small **increase in PR interval**
dizziness
headache
nausea
75
Phenytoin MOA
blocks voltage gated Na channels
dec glutamate
76
Phenytoin Clinical app
Gen t-c
focal aware/impaired
77
Phenytoin p-kin and interactions
_**\*\*\*Box warning: CV risk w/rapid infusion**_
variable absorption, dose-dependent elimination, protein binding, many drug int.
78
Phenytoin ADE
**ataxia**
**nystagmus**
**gingival hyperplasia**
**hirsutism**
**neuropathy**
**folate deficiency**
**MBD**
79
Phenobarbital MOA
Enhances GABAa receptor responses
80
Phenobarbital Clinical app
gen t-c
focal aware/impaired
81
Phenobarbital p-kin and interactions
long 1/2 life
inducer of P450
many interactions
82
Phenobarbital ADEs
**sedation**
**intellectual blunting**
**MBD**
**behavior changes**
ataxia
83
Gabapentin MOA
blocks synaptic release machinery A2S
dec glutamate
84
Gabapentin Clinical applications
gen t-c
focal aware/impaired
85
Gabapentin p-kin and interactions
variable bioavailability
renal elimination
86
Gabapentin ADEs
**ataxia**
**somnolence**
**weight gain**
dizziness
87
What are the **6 FDA approved drugs** for **Focal onset (partial) seizures**?
**Carb**amazepine
**Laco**samide
**Pheno**barbital
**Phen**ytoin
**Topira**mate
**Val**proic Acid
**"Carbs lack phenophen topval"**
88
What **3 drugs** can be used in **focal onset (partial) seizures** as **refractory monotherapy or adjunct**?
Pregabalin
Vigabatrin
Perampanel
89
Pregabalin MOA
Blocks synaptic release machinery A2S
decreases glutamate
90
Pregabalin Clinical app
focal aware/impaired
91
Pregabalin P-kin and interactions
renal elimination
92
Pregabalin ADEs
**ataxia**
**somnolence**
**weight gain**
dizziness
93
Vigabatrin MOA
GABA transaminase enhancing GABA activation
94
Vigabatrin clinical app
focal aware/impaired
95
Vigabatrin p-kin and interactions
renal elimination
96
Vigabatrin ADEs
_**\*\*Box warning: permanent vision loss**_
drowsiness, dizziness, psychosis, ocular effects
97
**MOA:** blocks postsynaptic ionotropic glutamate receptors AMPA, dec glutamate
**Clinical app:** focal aware/impaired
**P-kin:** multiple metabolites with long 1/2 lifes
**Interactions:** substantial, with increased clearance caused by CYP3A
What drug?
Perampanel
98
What drugs would you use for myoclonic seizures?
FDA approved:
levatriacetam
Alt:
Clonazepam
Topiramate
Valproic Acid
Zonisamide
99
Drugs with minimal or rare interactions
Gabapentin
Levetiracetam
Pregabalin
Vigabatrin
100
