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Anti-seizure Medications Flashcards

1
Q

AE’s are common and contribute to…

A

Treatment failure in up to 40% of patients, due to non-adherence

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2
Q

Most common AE’s with ASM’s are…

A

Dose-dependent, predictable, and reversible

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3
Q

Common CNS AE’s include…

A

Sedation, dizziness
Blurred or double vision
Ataxia
Difficulty concentrating

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4
Q

Common GI AE’s include…

A

Nausea, vomiting

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5
Q

Idiosyncratic reactions from ASM’s usually develop…

A

Within the first few weeks of treatment; unpredictable, but uncommon/rare

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6
Q

An example of a hypersensitivity reaction is…

A

SJS, TENS

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7
Q

SJS/TENS is most likely to occur with…

A

Phenytoin
Carbamazepine
Lamotrigine

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8
Q

Cross-sensitvity of hypersensitivity between agents…

A

Is possible, due to aromatic hydrocarbon ring

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9
Q

Drugs with an aromatic hydrocarbon ring include…

A

Carbamazepine + its derivatives
Phenobarbital
Primidone
Phenytoin
Lamotrigine

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10
Q

ASM exposure during pregnancy has been associated with…

A

Major congenital malformations and neurodevelopmental delay in offspring

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11
Q

General measures to consider for women taking ASM’s include…

A

Discussing pregnancy plans prior to conception
Ensure adequate folic acid supplementation
Aim for seizure-freedom for 9-12 months prior to pregnancy

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12
Q

Prevention of teratogenicity may include…

A

Avoiding valproic acid in women of childbearing potential
Avoid polytherapy + use lowest effective dose of ASM
Avoid stopping ASM’s or switching medications during pregnancy

Be mindful of risk to baby + mom with uncontrolled seizures

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13
Q

Adding a new ASM will often interfere…

A

With the levels of an existing ASM - strong CYP inducers + inhibitors are common

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14
Q

Hormonal contraceptives are involved with drug interactions via…

A

Enzyme inducing ASM’s reduce efficacy of COC (phenytoin, carbamazepine, phenobarb, primidone). Estrogen containing contraception will reduce lamotrigene levels

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15
Q

Preferred contraceptives for someone on ASM is…

A

LGN-IUD, copper IUD, or progesterone implant
Depot-medroxyprogesterone
COC with >30mcg EE taken continuously

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16
Q

Therapeutic drug monitoring is available for many older ASM’s, but…

A

There is a poor correlation between levels and clinical efficacy

Variability in patient response + seizure type

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17
Q

A drug level could be drawn when…

A

Desired clinical response - establish individual therapeutic range
Determining magnitude of dose increase, esp. with dose-dependent PK
Signs/sx’s suggestive of ASM toxicity
Assess if alteration in PK/formulation change drug level

Unexpected change in clinical response/poor compliance expected

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18
Q

1st line options for focal seizures as per AAN guidelines include…

A

Carbamazepine + Lamotrigine

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19
Q

2nd line options for focal seizures as per AAN guidelines include…

A

Levetiracetam
VPA
Oxcarbamazepine
Zonisamide

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20
Q

3rd line agents for generalized motor seizures (tonic-clonic) as per NICE guidelines include…

There are no 1st/2nd line agents listed in AAN due to lack of evidence

A

Carbamazepine
Lamotrigine
Valproate
Topiramate
Levetiracetam

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21
Q

1st and 2nd line agents for generalized motor myoclonic seizures as per NICE guidelines include…

A

1st line: Valproate
2nd line: Levetiracetam, topiramate

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22
Q

Medications that NEED to be avoided in generalized motor myoclonic + absence seizures include…

A

Carbamazepine + derivatves
Gabapentin
Phenytoin
Tiagabine
Vigabatrin
Lamotrigine in myoclonic only

May precipitate or aggravate seizures - importance of an accurate diagnosis

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23
Q

1st and 2nd line medications for absence seizures as per AAN guidelines include…

A

1st line: ethosuximide, valproate
2nd line: lamotrigine

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24
Q

Most common MOA of ASM is…

A

Sodium channel blockers - blocking sodium ion flow in neurons alters signal transduction

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25
ASM's that are sodium channel blockers are...
Phenytoin Carbamazepine + derivatives Lamotrigine Lacosamide Rufinamide
26
Phenytoin is a ____ spectrum ASM.
Narrow
27
Phenytoin place in therapy is...
Treating status epilepticus Last line for focal seizures, NOT for absence/myoclonic seizures
28
Advantages to phenytoin include...
OD/BID dosing, many dosage forms Cheap Extensive experience Defined therapeutic serum concentration range
29
Disadvantages to phenytoin include...
Substrate + broad spectrum inducer of CYP and glucuronidation - MANY drug interactions **Complicated PK, saturable kinetics** (therapeutic drug monitoring necessary) Lots of AE's
30
Dose-related toxicities of phenytoin may involve...
Mainly CNS: Drowsiness, confusion, nystagmus, ataxia, slurred speech, unusual behaviour, mental changes, coma Nausea ## Footnote (Levels > 200 umol/L)
31
Non-dose related toxicities of phenytoin may involve...
Hirsutism, acne, **gingival hyperplasia**, folate deficiency, osteomalacia, hypersensitivity reactions (SJS), lupus
32
Carbamazepine place in therapy for seizures is...
1st line for focal onset seizures 3rd line for generalized tonic-clonic
33
Carbamazepine is a ____ spectrum ASM.
Narrow
34
Advantages of carbamazepine include...
CR/XR tablets - BID dosing Can be used for other indications such as bipolar or neuropathic pain
35
Disadvantages of carbamazepine include...
Significant DI's Lots of AE's Risk of SJS + TENS
36
Carbamazepine has a lot of drug interactions due to...
Substrate + broad-spectrum inducer of CYP enzymes and **induces its own metabolism**, resulting in increased clearance and decreased half-life with continued dosing
37
Carbamazepine CYP inducing effect starts within ____ and ends in...
Within 24 hours, ends in 1-5 weeks. Applies to every dose increase
38
Dose related AE's with carbamazepine include...
GI - N/V, constipation, dry mouth CNS - lethargy, sedation, dizziness, blurred vision, ataxia CV - tachycardia, hypotension, conduction abnormalities
39
Some idiosyncratic AE's with carbamazepine include...
Hyponatremia Blood dyscrasias Rash + hypersensitivity rxns Weight gain Hepatic and thyroid issues Menstrual disturbances
40
These lab values should be monitored with carbamazepine usage...
LFT's + Thyroid Renal fx CBC with diff + platelets Electroytes ECG Bone mineral density
41
These patients have increased risk of rash + hypersensitivity reactions with carbamazepine:
Asian ancestry + HLA-B1502 Caucasian + HLA-A3101
42
Chronic usage of carbamazepine may lead to...
Osteomalacia Vitamin D deficiency
43
Notable drugs that will increase carbamazepine levels include...
Macrolides Antifungals CCB's Other ASM's - valproic acid + lamotrigine
44
Common drugs that may decrease carbamazepine levels include...
Other ASM's - phenytoin, phenobarbital, primidone
45
Notable drugs that have their serum levels decreased by carbamazepine include... | A LOT
Antipsychotics Antidepressants **Anticoagulants Antifungals Estrogen/progesterone Other ASM's - phenytoin, valproic acid, lamotrigine**
46
Eslicarbazepine MOA is ____, and is approved for...
Inhibition of voltage gated sodium channels - mono or adjunctive tx for focal seizures
47
Eslicarbazepine DI's compared to carbamazepine is...
Less severe - still induces 3A4, but no autoinduction
48
Eslicarbazepine AE's compared to carbamazepine is...
Similar, but frequency is less for all sx's.
49
Eslicarbazepine severe AE includes ____ and cannot be used if...
Prolongation of PR interval - CI if 2nd/3rd degree AV block
50
Oxcarbazepine is a prodrug structurally related to carbamazepine, and its difference is...
Adjusted to try and reduce frequency of AE's and severity DI's
51
Lamotrigine MOA is...
Blockage of sodium channels + reducing glutamate release Weak serotonin receptor inhibitory effect
52
Lamotrigine is a ____ spectrum ASM
Broad
53
Lamotrigine place in therapy includes...
1st line for focal seizures 3rd line for generalized motor seizures 2nd line for absence seizures ## Footnote Not for myoclonic
54
Advantages of lamotrigine include...
Well-tolerated Broad spectrum activity One of the safest in pregnancy Fewer DI's Good for bipolar depression
55
Disadvantages of lamotrigine include...
Does have clinically important DI's Slow titration required, not good if therapeutic levels are required quickly - risk of life-threatening rashes
56
Lamotrigine DI's that are important to note include...
Other ASM's - VPA, other enzyme-inducing ASM's Estrogen products All decrease lamotrigine levels
57
Lamotrigine titration is usually as follows...
Week 1-2: 25mg once daily Week 3-4: 50mg once daily Week 5: 100mg once daily Then increase dose by 50mg-200mg every 1-2 weeks
58
Common AE's that occur with lamotrigine include...
Sedation/insomnia, headaches, nausea, dizziness
59
Serious but rare AE that we must monitor in lamotrigene usage includes...
**Life-threatening SJS/TENS** Blood dyscrasias
60
85% patients on lamotrigene who experience SJS rash have prodromal symptoms, which involve...
Flu-like symptoms
61
The following needs to be monitored while on lamotrigine...
Baseline hepatic + renal function Monitor for rash CBC, LFT, SCr
62
Lamotrigine titration needs to be restarted if ____ days are missed, to avoid...
5 days - avoid increased risk of skin rash
63
Lacosamide is a newer ASM that is a ____ spectrum ASM, and is approved for ____ seizures.
Narrow, but maybe broad spectrum - approvaed for focal seizures
64
MOA of lacosamide is also...
Slow inactivation of voltage-gated sodium channels, inhibiting repetitive neuronal firing
65
Lacosamide has few DI's, but notably...
Has no contraceptive interactions
66
Lacosamide AE's are similar to other sodium channel blockers, which include...
CNS - dizziness, headache, ataxia, fatigue, diplopia, nystagmus, tremor GI - nausea, vomiting, diarrhea
67
Serious AE's with lacosamide include...
Hypersensitivity skin reactions Dose-dependent prolongation in PR interval, 1st degree AV block, afib/flutter ## Footnote Skin rxn thought to be cross-reactive with other agents
68
Clobazam's MOA is... | This is a BZD
Bind to GABA receptors to facilitate increased endogenous GABA binding activity
69
Clobazam is a ____ spectrum ASM
Broad
70
Clobazam place in therapy is...
3rd/4th line, or adjunct tx. for most seizure types. (both focal + generalized - including myoclonic, atonic)
71
Compared to other BZD's, clobazam is less likely...
To develop tolerance ## Footnote BZD's are usually not well-suited for chronic management due to rapid development of tolerance - this one is less likely
72
Advantages of clobazam include...
Broad-spectrum Rapid onset OD/BID dosing, cheap Few DI's
73
Disadvantages of clobazam include...
Possible tolerance (but less likely than other BZD's) Potential for abuse + dependence Needs to be weaned off to avoid withdrawal, if stopping
74
In general, if we are stopping ASM's, we should ____, because...
Taper - stopping immediately may worsen seizures ## Footnote Going from "seizure protective" to "no protection"
75
Primary AE's with clobazam include...
CNS effects - drowsiness, dizziness, ataxia, reduced concentration ## Footnote Some people develop tolerance
76
With clobazam, we should monitor...
Level of sedation Respiratory depression (especially with concurrent opioids)
77
MOA of phenobarbital is...
Bind to GABA receptors to prolong the activity of GABA
78
Phenobarbital is a ____ spectrum ASM
Narrow
79
Phenobarbital place in therapy is...
Not listed in AAN. 4th line for focal seizures and 3rd line for generalized TC seizures as per ILAE Declining use due to AE's and DI's
80
Advantages with phenobarbital include...
OD dosing, due to long half-life Cheap
81
Disadvantages with phenobarbital include...
Substrate + broad-spectrum inducer of various CYP enzymes and glucuronidation = many DI's **Prominent sedation** Lethality in overdose
82
Notable AE's with phenobarbital include...
CNs effects - **sedation** Rash Decreased vitamin D, folic acid Hepatotoxicity
83
If someone were to take phenobarbital, we would monitor...
Serum levels (target therapeutic range available) LFT's + renal function CBC's
84
MOA of topiramate is... | Combination
Blocks sodium channels Enhances GABA Antagonizes AMPA glutamate receptors Weakly inhibits carbonic anhydrase
85
Topiramate is a ____ spectrum ASM
Broad
86
Topiramate place in therapy is...
4th line for focal seizures (AAN) 3rd line for generalized tonic-clonic seizures (AAN) 2nd line for myoclonic seizures (NICE) 3rd line for absence seizures (NICE)
87
GABA is the major ____ neurotransmitter, involved in seizure activity
Inhibitory
88
One advantage with topiramate is that it may assist with...
Migraine prophylaxis Weight loss Alcohol dependence
89
Topiramate is generally not well tolerated due to the multitude of AE's, such as...
**CNS - drowsiness, dizziness, paresthesias, decreased concentration + cognition** Nausea, diarrhea **Renal stones, metabolic acidosis** Weight loss
90
Glutamate is the major ____ neurotransmitter, thought to increase seizure activity
Excitatory
91
MOA of perampanel is...
AMPA (Glutamate) receptor antagonist
92
Place in therapy of perampanel is...
Adjunctive tx of generalized tonic-clonic seizures, may also help with adjunctive tx with focal seizures
93
Perampanel is a ____ spectrum ASM
Broad
94
Common AE's with perampanel include...
CNS - dizziness, drowsiness, fatigue, ataxia, abnormal gait, irritability GI - vomiting, nausea Skin rash Pain (MSK, arthralgia, myalgia, back pain)
95
Black box warning on perampanel is... | CNS + Irritability AE's may lead to...
Psychiatric and behavioural reactions - aggressive behaviour and homicidal thoughts ## Footnote Appears to be dose-dependent
96
Valproic acid MOA is...
Increasing GABA activity through several mechanisms Modulates sodium, calcium, and potassium channels
97
Divalproex compared to valproic acid...
Has better GI tolerance
98
VPA is a ____ spectrum ASM
Broad - *option for practically all seizure types*
99
Divalproex place in therapy includes...
2nd line - focal seizures 3rd line - generalized tonic-clonic 3rd line - myoclonic 1st line - absence
100
Advantages with divalproex include...
Very broad spectrum - useful for other psychiatric + neurologic conditions Low risk of rash, no cross-reactivity
101
Disadvantages with divalproex include...
Inhibition of CYP enzymes - many potential DI's Well known teratogen May contribute to metabolic syndrome
102
Lamotrigine and valproic acid have a key drug interaction in that...
Lamotrigine concentrations are increased by ~50%, so we have to decrease lamotrigene dose by 50%
103
Notable side effects of valproic acid include...
GI: N/V/D, constipation, anorexia CNS: Tremor, sedation, ataxia, dizziness Thrombocytopenia Hair loss/thinning, weight gain, amenorrhea
104
Some serious adverse effects of valproic acid include...
Increased transanimases, LDH; hepatotoxicity Pancreatitis Hyperammonemia Leukopenia Skin rash (increased with lamotrigene usage)
105
With chronic usage of valproic acid, the following may occur...
Weight gain (up to 8-14kg) Menstrual disturbances; PCOS Alopecia
106
The following should be monitored with valproic acid usage...
Sedation Rash CBC, platelets, and LFT's Ammonia levels (unexplained lethargy, confusion, vomiting) Valproate levels
107
How often should valproate levels be tested?
2-4 days after a dose change or an interacting drug is started, then in 1-2 weeks to ensure stability Then PRN
108
Therapeutic range of valproic acid is...
350-700 micromol/L of total valproic acid; **guideline only and needs to be individualized**
109
Valproic acid levels should be taken...
At a steady state trough level; 3-4 days after initial therapy Or at suspected s/sx's of valproic acid toxicity
110
MOA of levetiracetam is...
Full mechanism unclear - binds to synpatic vesicle protein SV2A in presynaptic terminal to modulate NT release
111
Levetiracetam is a ____ spectrum ASM.
Broad
112
Levetiracetam's place in therapy for seizure management is...
2nd line for focal 3rd line for generalized TC seizures 2nd line or adjunct tx for myoclonic seizures
113
Advantages of levetiracetam include...
Different MOA, easy to be added No significant DI's (COC still affected) Very-well tolerated, low risk of rash Can be titrated rapidly with loading doses
114
Disadvantages of levetiracetam include...
Psychiatric/behavioural prbolems may limit therapy Renal dosing adjustments necessary
115
Common AE's with levetiracetam include...
CNS - sedation most common GI **Behavioural/psychiatric symptoms** ## Footnote Mood swings - agitation, aggression, anxiety, depression
116
Rare AE's with levetiracetam include...
Decrease in WBC's SJS, TEN
117
Monitoring with levetiracetam can include...
CBC's, if clinically indicated Renal function
118
Brivaracetam's MOA is...
Same as levetiracetam - binds to SVA2 protein
119
Brivaracetam is considered a ____ spectrum ASM.
Broad
120
So far, brivaracetam is approved for...
Adjunctive tx for focal seizres, not controlled with 1st line ASM's
121
Brivaracetam AE's are similar to levetiracetam, except for...
Lower risk of psychiatric disturbance (clinically, may still be similar) Low risk of bronchospasm or angioedema
122
IN GENERAL, broad-spectrum ASM's are...
Often effective at treating focal AND generalized seizures
123
IN GENERAL, narrow-spectrum ASM's are...
Used primarily for focal seizures

Seizures (4 decks)

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