Seizures Flashcards
1
Q
What is a seizure?
A
A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
2
Q
What is epilepsy?
A
Disorder of the brain characterized by an enduring predisposition to generate epileptic seizures.
3
Q
The clinical definition of epilepsy is?
A
Diagnosis expanded to include patients with only 1 unprovoked seizure but at significant risk of seizure recurrence
4
Q
What is the etiology of seizures? (5)
A
Variable causes, largely unknown
1. Genetics
2. Structural lesions in the brain acquired or genetic
3. Metabolic disorders
4. Infections
5. Immune
Anything that disturbs the normal functioning of the cerebral cortex can cause seizures, and if this abnormality is enduring, it can result in epilepsy.
5
Q
Synchronous hyperexcitability underyling seizures may be due to: (5)
A
- Increased excitatory synaptic neurotransmission
- ↓ inhibitory synaptic neurotransmission
- Alteration of voltage-gated ion channels
- Alteration of intra- or extracellular ion concentrations
- Hypersynchrony
- Recruitment of neighbouring neurons into an abnormal firing mode
6
Q
What is the impact of seizures on patient’s lives? (7)
A
- Stigma person living with epilepsy (not epileptic person)
- Fear of seizures nature & unpredictability of szs
- Injuries
- Hospitalizations
- Lost productivity
- Anxiety & MDD
- Increase mortality 2-3x higher than general population
7
Q
Seizures are differentiated into 3 primary types of onset. What are they?
A
- Focal
- Generalized
- Unknown
8
Q
What is a focal seizure?
A
Originate within networks limited to one hemisphere
9
Q
What is a generalized seizure?
A
Originate at some point within, and rapidly engaging, bilaterally
distributed networks
10
Q
What are “unknown” seizures?
A
Reflects the difficulty to classify unwitnessed seizures and those that occur while the patient is asleep
11
Q
What is status epilepticus?
A
Any seizure that does not stop within 5 minutes should be treated as impending status epilepticus (SE)
- Operationally seizures lasting >5 mins or repetitive seizures for > 5 min are treated as SE to prevent consequences and increase response to tx
12
Q
Patients are often given __ ______ benzodiazepines to use ___ at the onset of seizures to decrease risk of progression to SE
A
on demand
prn
13
Q
What “on demand” benzo might be given to an adult, pediatric, and infant <3 months to treat an acute seizure?
A
Adults commonly - lorazepam sublingual
Pediatrics - midazolam intranasal or buccal
Infants - rectal diazepam
14
Q
What are some steps to take in seizure first aid in a person experiencing a convulsive seizure? (9)
A
- Don’t panic - you can help
- Time it. Longer than 5 mins = call an ambulance
- Explain what is going on. Ask to be given space
- Cushion head and neck with something soft
- Roll the person to their side to prevent choking
- Clear the area of dangers
- Do NOT put anything in the mouth
- Do NOT restrain
- Speak gently. Be kind during and after the seizure
15
Q
Epilepsy is diagnosed based on what?
A
A combo of clinical history and physical/neuro exam
16
Q
What are some classes of meds that can lower seizure threshold? (7)
A
- Analgesics
- Anticancer drugs
- Antimicrobials
- Immunosuppressants
- Psychiatric meds
- Stimulants
- Sympathomimetics and decongestants
17
Q
What does it mean to lower seizure threshold?
A
Easier for a seizure to happen
18
Q
What does an EEG help with in seizure diagnosis? (3)
A
- Both interictal (before/after sz) and ictal (during sz) recordings are informative
- Screening for epileptiform discharges - Used to determine if focal vs. generalized onset, and estimating risk of recurrence
- Only a snapshot in time so some patients may require multiple EEGs or admission to an inpatient unit that does continuous EEG monitoring
19
Q
What does brain imaging help with in seizure diagnosis? (2)
A
- Used to identify structural abnormalities (e.g., focal lesions, brain tumour)
- NOT to observe seizure activity
20
Q
What labs studies might be done in epilepsy diagnosis? (4)
A
- Blood glucose
- CBC with diff
- Electrolyte panels (esp. sodium)
- Lumbar puncture (if suspicion of meningitis or encephalitis)
21
Q
What are the goals of therapy for a seizure patient? (5)
A
- Complete seizure control (within minutes if status epilepticus then ongoing)
- ↓ seizure frequency, severity, type (ongoing)
- In the 30%–40% of patients that do not achieve complete seizure control - Reduce morbidity and mortality (ongoing)
- Improve quality of life (ongoing)
- Minimize ADEs
22
Q
Epilepsy is generally well controlled with ___________ or _______
A
medications; surgery
23
Q
Some patients may require treatment with antiseizure meds in the short term, but these are generally not continued once the patient’s medical problem has been resolved. Give 3 examples of types of patients
A
Patients with acute seizures from:
1. Metabolic (e.g., uremia, hypoglycemia, hyperglycemia, hepatic failure)
2. Toxic (e.g., drug overdose or withdrawal)
3. Infectious (e.g., meningitis) etiologies
24
Q
Long-term treatment of seizures is usually considered when?
A
Once diagnosis of epilepsy is made
25
What are the principles for initiating ASM therapy? (2)
1. Start with monotherapy
2. Titrate slowly
- Start ASM at 1/4 to 1/3 of the initial dose and increase q1-2weeks
- Unless status epilepticus or high risk for harm from seizures --> loading doses
- Minimizes risk of dose-dependent adverse effects
- Patient-specific factors may affect the speed of titration (e.g., titrate over months in the elderly vs. over days if frequent seizures)
26
What is the epilepsy treatment approach when there is inadequate response to initial therapy? (3)
1. Inquire about medication adherence
- Reported that 60% are nonadherent
2. If at a moderate dose with few adverse effects, titrate up to max dose
3. If continuing to experience breakthrough seizures at maximum tolerable dose, consider:
- Initiate a different 1st line ASM as monotherapy start new agent, taper off old (unless intolerable ADEs)
- Initiate combination therapy by adding a 2nd ASM
27
What are the pros of ASM monotherapy? (3)
1. Fewer idiosyncratic reactions
2. Increases probability of adherence
3. More cost-effective
- ~65% of patients can be maintained on monotherapy
28
Polytherapy is usually reserved for patients who...
have failed monotherapy with 2-3 drugs
- Typically select an ASM with a different or complimentary MOA
29
Not all pts require lifelong ASM therapy.
What is the benefit to stopping?
What are the 2 risks?
Benefit:
- Discontinuing 1+ medication will reduce polypharmacy and may decrease adverse effects and improve cognition
Risk:
- Risk of recurrent seizures (impacts driving, personal safety, and psychological well-being)
- Seizure control may be lost long-term
30
What are 4 factors favoring successful discontinuation of ASM(s)?
1. Seizure-free
- 2 years for children
- 2 to 5 years for adults
2. Normal neurologic exam
3. Normalized EEG with treatment
4. History of single type of focal seizure or generalized tonic-clonic seizures
31
What is the best approach to stopping ASM treatment? (3)
1. If non-emergency situation, slow and gradual taper is best to prevent relapses and status epilepticus
2. If on >1 ASM, each one should be withdrawn separately
3. No optimal rate of withdrawal of ASM(s) has been identified, but a schedule of at least 6 weeks seems to be safe
- Versus 9-month period in clinical trial; no different
32
What are the 3 main non-pharmacologic therapies for epilepsy/seizures?
1. Diet
2. Surgery
3. Vagus Nerve Stimulation (VNS)
33
What sort of dietary changes can help with seizures? (4)
1. Diet: Ketogenic diet
2. High fat, low carb, adequate protein diet mimics state of starvation
- Requires strict compliance
- Poorly tolerated by patients
3. May reduce seizure frequency
- Anti-epileptic mechanisms not fully established
4. Consider if have not responded to appropriate ASM therapy
34
When is surgery an option for seizures?
An option for some patients with refractory focal onset epilepsy resistant to multiple ASMs
- The majority of pts achieve seizure-freedom
35
What is vagal nerve stimulation?
When might it be used? (4)
1. Involves a surgical procedure to implant an electrical pulse generator in the chest and attach electrodes to the vagus nerve in the neck
2. Pulse generator stimulates the vagus nerve on a regularly scheduled basis
3. May reduce seizure frequency
- Mechanism is unknown
4. Option in refractory focal onset or generalized seizures
36
What are some general measures of non-pharmacologic therapy to help prevent seizures? (4)
1. Adequate sleep/nutrition
2. ↓ stress/anxiety
3. ↓ alcohol
- Avoid abrupt withdrawal if heavy use
4. Avoid triggers
- Photosensitivity
- Loud sounds
- Caffeine
- Flashing lights
- Heat/overexertion
37
What are some considerations to be aware of when thinking of choosing ASM? (9)
1. MOA – in relation to sz type
2. Evidence of benefit/consensus recommendations
3. Comorbidities
4. Adverse drug effects
5. Teratogenicity
6. Drug interactions
7. Therapeutic drug monitoring
8. Formulations
9. $$$/coverage
38
What are the MOAs of different epilepsy pharmacotherapies? (6)
1. Modulation of voltage-gated ion channels
- Sodium, potassium, calcium
2. ↑ inhibitory effect of gamma-aminobutyric acid (GABA)
3. Modulation of synaptic release
4. Inhibition of synaptic excitation
5. Glutamate receptor activity
6. AMPA receptor activity
39
Most common ADEs of ASMs are ____-_________ and __________
dose-dependent; reversible
40
What are the CNS side effects of ASMs? (5)
1. Sedation**
2. Dizziness**
3. Blurred or double vision
4. Ataxia
5. Difficulty concentrating
41
What are the GI side effects of ASMs? (2)
1. Nausea
2. Vomiting
42
What are 2 hypersensitivity reactions that can occur with ASMs?
1. SJS
2. TEN
43
Hypersensitivity reactions to ASMs are most likely to occur with which meds? (4)
1. Phenytoin
2. Carbamazepine
3. Lamotrigine
4. ?Lacosamide
44
Cross-sensitivity between ASM agents is possible why?
Due to aromatic hydrocarbon ring
45
What anti-epileptic drugs should be avoided if a patient develops a phenytoin-related rash? (7)
1. CBZ
2. Oxcarbazepine
3. Eslicarbazepine
4. Phenobarbital
5. Primidone
6. Phenytoin
7. Lamotrigine
46
What anti-epileptic drugs are safe to switch to if a patient develops a phenytoin-related rash? (7)
1. Clobazam
2. Gabapentin
3. Pregabalin
4. Lacosamide
5. Levetiracetam
6. Topiramate
7. VPA
47
ASM exposure during pregnancy has been associated with major congenital malformations and neurodevelopmental delay in the offspring. What are some general measures to take then? (4)
1. Discuss pregnancy plans prior to conception
2. Consider teratogenic effect of ASM for all women of reproductive age
3. Ensure adequate folic acid supplementation
4. Aim for seizure-freedom for 9-12 months prior to pregnancy
48
If possible, avoid which ASM med in women of childbearing age?
VPA
49
What are 2 preferred ASM drugs to use in women of childbearing age?
1. Lamotrigine
2. Levetiracetam
50
Which 3 ASM drugs are strong CYP inducers?
1. Phenytoin
2. CBZ
3. Phenobarbital
51
Which ASM drug is a CYP inhibitor?
VPA
52
What DIs is there to be aware of with hormonal contraceptives? (2)
1. Many enzyme-inducing ASMs reduce the efficacy of combined hormonal contraceptives
- E.g., phenytoin, carbamazepine, phenobarbital, primidone
2. Estrogen containing OCP reduces lamotrigine levels
53
What are the preferred contraceptives to use if patient is on ASM? (3)
1. LNG-IUD or copper IUD or progesterone implant
2. Depot-medroxyprogesterone
3. COC with ≥30mcg EE taken continuously
54
Therapeutic Drug Monitoring:
When to draw an ASM level? (8)
1. Once the desired clinical response has been achieved, to establish the “individual therapeutic rangeâ€
2. To assist the clinician in determining the magnitude of a dose increase, particularly with ASMs showing dose-dependent pharmacokinetics (most notably, phenytoin)
3. When there are uncertainties in the differential diagnosis of signs or symptoms suggestive of concentration-related ASM toxicity, or when toxicity is difficult to assess clinically (e.g. in young kids)
4. When seizures persist despite an apparently adequate dosage.
5. When an alteration in pharmacokinetics (and, consequently, dose requirements) is suspected, due to age-related factors, pregnancy, associated disease, or drug-drug interactions.
6. To assess potential changes in steady state ASM concentration when a change in drug formulation is made, including switches involving generic formulations.
7. Whenever there is an unexpected change in clinical response.
8. When poor compliance by the patient is suspected.
55
How are ASMs classified based on spectrum of activity? (2)
1. Narrow
- Generally effective for focal seizures
- Less effective for and may exacerbate idiopathic epilepsy syndromes (myoclonic, absence)
2. Broad
- Generally effective against all seizure types
56
Name the ASMs that fall under the narrow spectrum of activity category (8)
1. Carbamazepine
2. Gabapentin
3. Oxcarbazepine
4. Phenytoin
5. Phenobarbital
6. Pregabalin
7. Tiagabine
8. Vigabatrin
57
Name the ASMs that fall under the broad spectrum of activity category (9)
1. Brivaracetam
2. Felbamate
3. **Lamotrigine**
4. **Levetiracetam**
5. **Perampanel**
6. **Topiramate**
7. Rufinamide
8. **Valproate**
9. Zonisamide
58
What ASM falls under both narrow and broad spectrum of activity?
Lacosamide
59
What are the 2 first line ASMs for focal seizures (motor/nonmotor)?
1. Carbamazepine
2. Lamotrigine
60
What are the 4 second line ASMs for focal seizures (motor/nonmotor)? (LOVZ)
1. Levetiracetam
2. VPA
3. Oxcarbazepine
4. Zonisamide
61
What are the 3 fourth line (there are no 3rd lines for this condition) ASMs for focal seizures (motor/nonmotor)?
1. Gabapentin
2. Topiramate
3. Phenytoin
62
What are the third line ASMs for generalized motor (tonic-clonic) seizures? (5) (only have third line available, insufficient evidence for something to be first line)
1. CBZ - 1st line in NICE guidelines
2. Lamotrigine - 2nd line in NICE guidelines
3. Valproate
4. Topiramate
5. Levetiracetam
63
What is the first line ASM for generalized motor (myoclonic) seizures?
Valproate (NICE guidelines)
64
What are the 2 second line ASMs for generalized motor (myoclonic) seizures?
1. Levetiracetam (NICE guidelines)
2. Topiramate (NICE guidelines)
65
What are the 4 third line ASMs for generalized motor (myoclonic) seizures?
1. Clobazam
2. Clonazepam
3. Piracetam
4. Zonisamide
66
What are the 3 adjunctive ASMs for generalized motor (myoclonic) seizures? (NICE guidelines) (LTV)
1. Levetiracetam
2. Valproate
3. Topiramate
67
What ASMs should be avoided in generalized motor (myoclonic) seizures AND generalized nonmotor (absence) seizures as they may precipitate or aggravate myoclonic and absence seizures? (7)
1. Carbamazepine
2. Gabapentin
3. Oxcarbazepine
4. Phenytoin
5. Pregabalin
6. Tiagabine
7. Vigabatrin
68
What are 2 first line ASMs for generalized nonmotor (absence) seizures?
1. Ethosuximide
2. Valproate
69
What is the second line ASM for generalized nonmotor (absence) seizures?
Lamotrigine
70
The most common MOA of ASMs is what?
Blocking Na+ ion flow in neurons, altering signal transduction (aka sodium channel blockers)
71
What are the 6 sodium channel blocking ASMs?
1. Phenytoin
2. Eslicarbazepine
3. Carbamazepine
4. Lamotrigine
5. Lacosamide
6. Rufinamide (don't worry about this for this semester)
72
What place in therapy does phenytoin have? (4)
(i.e., what spectrum is it? what is it good for treating? focal seizures? when should it not be used?)
1. "Narrow-spectrum†ASM
2. Treating status epilepticus
3. 4th line for focal szs
4. NOT for absence or myoclonic seizures
73
What are the advantages of phenytoin? (5)
1. Daily or BID dosing
2. Parental and other dosage forms available
3. Cheap
4. Extensive experience
5. Defined therapeutic serum concentration range
74
What are the disadvantages of phenytoin? (3)
1. Substrate AND a broad spectrum inducer of various CYP enzymes and glucuronidation --> many drug interactions
2. Dosing complicated by saturable kinetics
3. Long-term cosmetic adverse effects (e.g., gingival hyperplasia)
75
What should you know about phenytoin kinetics? (2)
#NAME?
76
What are the dose related toxicities seen with phenytoin? (levels > 200umol/L) (9)
1. Drowsiness
2. Confusion
3. Nystagmus
4. Ataxia
5. Slurred speech
6. Nausea
7. Unusual behaviour
8. Mental changes
9. Coma
77
What are the non-dose related toxicites seen with phenytoin? (7)
1. Hirsutism
2. Acne
3. Gingival hyperplasia
4. Folate deficiency
5. Osteomalacia
6. Hypersensitivity reactions (including SJS)
7. SLE
78
What place in therapy does CBZ have? (4)
(i.e., what spectrum? focal seizures? GTC? when not used?)
1. “Narrow-spectrum†ASM
2. 1st line for focal onset seizures AAN 2018
3. 3rd line for GTC AAN 2018
4. NOT for absence or myoclonic seizures
79
What is an advantage of CBZ? (3 subpoints)
CR/XR tabs: bioequivalent with BID dosing vs. QID dosing with IR tabs
- CR/XR = lower peaks and higher troughs than IR --> may decrease dose-related side effects and improve seizure control
- May improve adherence
- Must conduct therapeutic drug monitoring to reassess levels if changing between formulation
80
What are 2 disadvantages of CBZ?
1. Substrate and broad-spectrum inducer of CYP enzymes --> many+++ drug interactions
- Induces its own metabolism, which complicates dose-adjustments
- Onset within 24 hours
- Time to completion 1 to 5 weeks
2. Risk of SJS and TEN
81
Who specifically cannot be given CBZ?
Asian ancestry + positive genetic test for HLA-B*1502
82
What are the GI dose-related side effects of CBZ? (3)
1. Nausea
2. Vomiting
3. Anorexia
83
What are the idiosyncratic side effects of CBZ? (3)
1. SIADH/hyponatremia
2. Blood dyscrasias
3. Hypersensitivty reactions (SJS)
84
What are the chronic side effects of CBZ? (2)
1. Osteomalacia
2. Vitamin D deficiency
85
What are 4 classes of drugs reported to increase CBZ levels?
1. Antibiotics
2. Anticonvulsants
3. Antifungals
4. CCBs
86
What antibiotics increase CBZ levels?
Macrolides
- Erythromycin
- Clarithromycin
- Telithromycin
87
What anticonvulsants increase CBZ levels? (2)
1. VPA
2. Lamotrigine
88
What antifungals increase CBZ levels?
Azoles
- Itraconazole
- Fluconazole
- Ketoconazole
89
What CCBs increase CBZ levels? (2)
1. Diltiazem
2. Verapamil
90
What anticonvulsants decrease CBZ levels? (3)
1. Phenytoin
2. Phenobarbital
3. Primidone
91
What classes of drugs are decreased BY CBZ? (4)
1. Anticoagulants
2. Anticonvulsants
3. Antifungals
4. Hormonal agents
92
What anticoagulant has levels decreased by CBZ?
Warfarin
93
What anticonvulsants have their levels decreased by CBZ? (3)
1. Phenytoin - variable effect
2. VPA
3. Lamotrigine
(Topiramate too)
94
What antifungals have their levels decreased by CBZ? (2)
1. Caspofungin
2. Azole derivatives
- Itraconazole
- Posaconazole
- Voriconazole contraindicated
95
What hormonal agents have their levels decreased by CBZ? (2)
1. Oral contraceptive pills
2. Products containing estrogen or progesterone
96
What are the approved indications for eslicarbazepine? (2)
1. Mono treatment for adult epilepsy patients with focal seizures
2. Adjunctive treatment for focal seizures (> 6 years old)
97
If CrCl <__mL/min, eslicarbazepine dose needs to be adjusted
50
98
What are the enzyme (drug) interactions seen with eslicarbazepine? (3)
1. Induces CYP3A4 (moderate)
2. Substrate of UGT2B4
3. No autoinduction
99
What is the serious side effects of eslicarbazepine?
Prolongation of PR interval (contraindicated if 2nd or 3rd degree AV block)
100
What are the CNS dose related side effects of basically all the ASMs? (6)
1. Dizziness
2. Drowsiness
3. Headache
4. Diplopia
5. Ataxia
6. Fatigue
101
What is the MOA of lamotrigine aside from Na channel blocking? (2)
1. Reduces release of glutamate
- Not clear whether this action is secondary to blocking the activation of the voltage-gated sodium channel
2. Weak 5-HT3 receptor inhibitory effect
102
What place in therapy does lamotrigine have?
(i.e., what spectrum? when is it used (4)? when is it not used?)
1. “Broad-spectrum†ASM
2. 1st line for focal onset seizures
3. 3rd line for generalized motor seizures
4. 2nd line for absence seizures
5. 2nd line for Lennox-Gastaut Syndrome
6. NOT myoclonic seizures
103
What are the advantages of lamotrigine? (5)
1. Generally well-tolerated
- Patients are more alert vs. other AEDs
- Weight neutral
2. Broad spectrum of seizure activity
3. One of the safest ASMs in pregnancy
4. NOT a broad-spectrum enzyme inducer (fewer DIs)
5. Excellent option if concomitant bipolar disorder
104
What are the disadvantages of lamotrigine? (4)
1. Drug interaction with COCs – ↓ lamotrigine ~50%
2. Risk of life-threatening rashes (SJS/TEN)
3. Very slow dose titration required (q2weeks or more)
- Not a good drug if therapeutic levels required quickly
4. Drug interaction with other ASMs
105
What ASM does lamotrigine interact with?
1. Valproic acid (VPA) inhibits metabolism of lamotrigine, requires 50% lower doses of lamotrigine
2. Enzyme-inducing AEDs will require higher doses of lamotrigine
106
What is the most important counselling tip about lamotrigine dosing?
Slow titration very very important to prevent SJS
107
If missed dose of lamotrigine for _ days then must restart titration
5
108
What are the ADEs of lamotrigine aside from drowsiness, fatigue, and dizziness? (5)
1. Nausea
2. Chest pain
3. Peripheral edema
4. Insomnia
5. Skin rash (non-serious)
109
What are the approved indications for lacosamide? (2)
1. Adjunctive treatment of focal seizures (adults)
2. Mono treatment of focal seizures (adults)
110
If CrCl <__mL/min then lacosamide dose needs to be adjusted
30
111
Lacosamide has few drug interactions, but what is one class to know about?
Antiarrhythmics - increased risk of bradycardia, V-tach, prolonged PR interval
112
What are the serious side effects of lacosamide? (3)
1. Dose-dependent prolongation in PR interval
2. Asymptomatic 1st degree AV block
3. Afib/flutter (case reports)
113
What is the contraindication of using lacosamide?
2nd or 3rd degree AV block
114
Name the ASMs that target calcium or potassium channels (7)
1. Ethosuximide (next semester drug)
2. Gabapentin
3. Pregabalin
4. CBZ
5. Eslicarbazepine
6. VPA
7. Zonisamide
115
ASMs that impact GABA activity have 3 different MOAs. What are they?
1. Reducing GABA breakdown
2. Increasing GABA availability
3. Mimicking GABA action on receptors
116
What are the ASMs that impact GABA activity? (3)
1. BZDs
- Clobazam, clonazepam, etc.
2. Barbituates
- Phenobarbital
3. Topiramate
(Others = tiagabine, vigabatrin)
117
What is the MOA of clobazam (really all BZDs)?
BZDs bind to GABA receptors to facilitate increased endogenous GABA binding activity
118
What place in therapy does clobazam have? (2)
1. “Broad-spectrum†ASM
2. Used 3rd or 4th line or as adjunct for most seizure types and Lennox-Gastaut syndrome
119
What are the advantages of clobazam? (6)
1. Less likely to develop tolerance vs. other BZDs
2. Broad-spectrum activity
3. Rapid onset
4. Daily or BID dosing
5. Cheap
6. Few drug interactions
120
What are the disadvantages of clobazam? (3)
1. Tolerance is possible
2. Potential for abuse and dependence
3. Must be weaned off to avoid withdrawal symptoms
121
What are the ADEs of clobazam? (2)
1. CNS effects
- Tolerance develops to some (e.g., sedation)
2. ↑ traffic accidents
122
What should be monitored when using clobazam? (2)
1. Sedation
2. Respiratory depression
123
What is the MOA of phenobarbital?
Binds to GABA receptors to prolong the activity of GABA
124
What is the place in therapy for phenobarbital? (3)
1. “Narrow-spectrum†ASM
2. 4th line for focal seizures
3. 3rd line GTC seizures
- Declining use due to adverse effects and many drug interactions
125
What are the advantages of phenobarbital? (2)
1. Once daily dosing due to long half-life
2. Cheap
126
What are the disadvantages of phenobarbital? (3)
1. Substrate AND a broad-spectrum inducer of various CYP enzymes and glucuronidation --> many drug interactions
2. Sedation is prominent
3. Lethality
127
What are the ADEs of phenobarbital? (5)
1. CNS effects
2. Sedation (often significant)
3. Rash 5-10% (rarely serious)
4. ↓ Vit D, folic acid
5. Hepatotoxicity (rare)
128
What is the MOA of topiramate? (4)
Combination of mechanisms
1. Blocks sodium channels
2. Enhances GABA (A)
3. Antagonizes AMPA glutamate receptors
4. Weakly inhibits carbonic anhydrase (CA)
- CA inhibition does not contribute to anti-seizure properties but causes ADEs (kidney stones, metabolic acidosis)
129
What place in therapy does topiramate have? (5)
1. Broad spectrum ASMâ€
2. 4th line for focal szs
3. 3rd line for GTC szs
4. 2nd line for myoclonic szs
5. 3rd line for absence szs
130
What is the advantage of topiramate?
May assist with migraine prophylaxis, weight loss, and alcohol dependence
131
What is the disadvantage of topiramate?
1. Generally not well tolerated due to CNS ADEs
- Drowsiness, dizziness, paresthesias, difficulty word finding, decreased concentration, decreased cognition
132
What are the ADEs of topiramate? (4)
1. Nausea, diarrhea
2. Renal stones 1.5% (increase fluid intake)
3. Weight loss (4kg, dose dept)
4. Rare:
- Metabolic acidosis, increased LFTs, reduced sweating (in children)
133
What are the ASMs that impact glutamate activity? (4)
1. Perampanel**
2. Zonisamide
3. Lamotrigine
4. Topiramate
134
What is the MOA of perampanel?
AMPA receptor antagonist
135
What are the approved indications of perampanel? (2)
1. Adjunctive treatment of PGTC seizures in adults (>= 18 y.o)
2. Expansion to focal seizures and PGTC (12-17 y.o)
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What spectrum is perampanel?
Broad
137
What are the 2 advantages of perampanel?
1. Novel MOA
2. Once daily dosing
138
What are the serious side effects of perampanel? (black box)
1. Psychiatric and behavioural reactions
- Aggressive behaviour and homicidal thoughts
139
True or False? DVP and VPA are interchangeable
False - same dosing, but not interchangeable
140
What is the MOA of VPA and DVP? (2)
1. GABA activity through several mechanisms
2. Modulates sodium, calcium, potassium channels
141
What place in therapy does VPA and DVP have? (6)
1. “Broad-spectrum†ASM
2. Option for practically all seizure types
3. 2nd line for focal seizures
4. 3rd line for GTC seizures
5. 3rd line for myoclonic seizures
6. 1st line for absence seizures
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What are the advantages of VPA and DVP? (4)
1. “Broad-spectrum†ASM, and useful for other psychiatric and neurologic conditions
- Useful if >1 indication for VPA (e.g., bipolar disorder + seizures)
2. Low risk of rash
- Does not cross react with aromatic hydrocarbon AEDs for hypersensitivity risk
3. Does NOT reduce the effectiveness of COCs
4. Should be dosed BID or TID for seizures
- Note in U.S. once daily extended release formulation available (not available in Canada
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What are the disadvantages of VPA and DVP? (3)
1. Inhibits CYP enzymes
- Many potential drug interactions
- E.g., Increases lamotrigine levels by 30 to 50%
2. Well-known teratogen
- Least desirable option in women of childbearing potential
- Also risk of PCOS, amenorrhea
- AVOID if possible!
3. Can contribute to metabolic syndrome
144
What is the unique thing to remember about carbamazepine metabolism?
It induces its own metabolism via the epoxide-diol pathway (AUTOINDUCTION)
145
What are the dose related ADEs of VPA/DVP? (4)
1. GI: nausea, vomiting, anorexia (reported to be lower with DVP vs VPA)
2. CNS: tremor, sedation, ataxia
3. Thrombocytopenia
4. Thinning or loss of hair, weight gain, amenorrhea
146
In VPA monitoring we only measure ammonia when?
Only if unexplained lethargy/confusion/vomiting
147
What is the therapeutic range for VPA (In umol/L)?
350-700 umol/L
148
What is the MOA of levetiracetam? (3)
1. Considerably different than other ASMs
2. Full mechanism unclear
3. Binds to synaptic vesicle protein SV2A in the presynaptic terminal to modulate neurotransmitter release
149
What place in therapy does levetiracetam have? (4)
1. "Broad-spectrum†AED
2. 2nd line for focal seizures
3. 3rd line for GTC seizures
4. 4th line adjunct for myoclonic seizures
150
What are the advantages of levetiracetam? (6)
1. Novel MOA
2. No significant drug interactions
3. Very well-tolerated
4. Low risk of rash
5. Allows rapid dose titrations & loading doses
6. Dosed BID
151
What are the disadvantags of levetiracetam? (2)
1. Psychiatric / behavioral problems might limit therapy
2. Renal dosing adjustments
152
What are the common ADEs of levetiracetam? (3)
1. CNS (sedation is most common)
2. GI
3. Behavioural / psychiatric symptoms in up to 30% of patients!!
- Mood swings are most common
- Agitation, aggression, anxiety, depression
153
What are the rare ADEs of levetiracetam? (3)
1. ↓ WBCs
2. SJS
3. TEN
154
What is important to monitor when using levetiracetam?
Renal function - requires renal dose adjustments
155
What is the MOA of brivaracetam?
Binds to SV2A protein
156
What is the approved indication for brivaracetam?
Adjunctive tx for partial onset seizures in adults not controlled with conventional ASMs
157
What are the serious ADEs of brivaracetam? (3)
1. Psychiatric disturbance
2. Bronchospasm
3. Angioedema
