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Psychiatric Pharmacotherapy > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

*What is a seizure?

A

Transient episode (s/sx) due to abnormal excessive/synchronous brain activity

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2
Q

*What is epilepsy?

A

Any of the following:

  1. 2 or more seizures >24 h apart
  2. 1 unprovoked seizure + 60% or more recurrence risk after 2 unprovoked seizures (over next 10 years)
  3. Epilepsy syndrome diagnosis
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3
Q

*What are some possible CNS insults that can provoke seizures in normal individuals?

A

Metabolic (Na, Ca, Mg, Glucose)
Infectious/Inflammation (fevers)
Structural (stroke, traumatic brain injury)
Toxic (illicit drugs, alcohol, BZD withdrawal)
(MIST)

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4
Q

*What is the pathophysiology of seizures/epilepsy?

A

Hyperexcitability + Hypersynchronization

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5
Q

What are some factors contributing to Hyperexcitability ?

A
  1. More ion channels
  2. Metabolic abnormalities
  3. Excessive excitatory neurotransmitter
  4. Insufficient inhibitory neurotransmitter
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6
Q

Examples of excitatory neurotransmitters?

A

glutamine, acetylcholine, histamine, cytokines,

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7
Q

Examples of inhibitory neurotransmitters?

A

GABA, dopamine

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8
Q

Focal onset refers to __ in the context of epilepsy.

A

Seizures beginning in only 1 hemisphere

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9
Q

Generalized onset refers to __ in the context of epilepsy.

A

Seizures beginning in both hemispheres

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10
Q

Dyscognitive features refers to __ in the context of epilepsy.

A

Impairment of consciousness

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11
Q

*How does ILAE classify seizures?

A
  1. Focal/generalized
  2. Dyscognitive features Y/N
  3. Other features
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12
Q

*For a conscious patient with focal onset seizures, what are the possible motor symptoms they may present with?

A

Clonic movement

Speech arrest

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13
Q

*For a conscious patient with focal onset seizures, what are the possible sensory symptoms they may present with?

A

Feelings of numbness/tingling
Visual disturbances
Rising epigastric sensation

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14
Q

*For a conscious patient with focal onset seizures, what are the possible autonomic symptoms they may present with?

A

HR, pallor, BP, Sweating, salivation

HPBSS

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15
Q

*For focal onset seizures without dyscognitive features, what are the possible psychic/somatosensory symptoms they may present with?

A

Hallucinations
Flashbacks
Affective symptoms (i.e. fear, depression, anger and irritability)
(HAF)

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16
Q

*For focal onset seizures with dyscognitive features, what are the possible symptoms they may present with?

A

Aura
Impaired consciousness
Automatisms (i.e. lip smacking, chewing or picking at their clothing unpurposefully)

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17
Q

*What is the tonic phase of generalized tonic-clonic (GTC) seizures characterized by?

A

Stiffening of limbs

Breathing may decrease or stop, possibly leading to cyanosis

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18
Q

*What is the clonic phase of generalized tonic-clonic (GTC) seizures characterized by?

A 
Jerking of limbs and face
Usually lasts 1minute 
Breathing typically resumes (may be noisy/ labored/ irregular)
Incontinence may occur
Biting of tongue or inside of mouth
(J1 BIB)
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19
Q

*How would a patient feel after a GTC seizure event?

A

Headache
Sleepy
Lethargic
Confused

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20
Q

*How long will full recovery take post a GTC seizure event?

A

Minutes to hours (depending on severity of episode)

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21
Q

*What are the characteristics of a generalized clonic seizure?

A

Clonic jerking is asymmetrical and irregular

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22
Q

Which patient group is most likely to present with generalized clonic seizures?

A

neonates, infants or young children

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23
Q

*What are the characteristics of a generalized tonic seizure?

A

Sudden loss of consciousness and rigid posture of entire body
Lasts 10-20 seconds

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24
Q

Which patient group is most likely to present with generalized tonic seizures?

A

Any age with diffuse cerebral damage and learning disability
Association with other seizure types i.e. Lennox Gastaut syndrome

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25
Q

*What are the characteristics of a generalized myoclonic seizure?

A

Involves rapid, brief contractions of bodily muscles, usually occurring on both sides of the body concurrently
- On occasion, may involve just one arm or one foot

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26
Q

*What are the characteristics of a generalized absence seizure?

A

Basic lapse in awareness that begins and ends abruptly

- Often mistaken as persistent staring

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27
Q

Which patient group is most likely to present with generalized absence seizures?

A
  • More common in children than in adults

- First onset usually occurs at 4-12 years old; rarely after 20 years old

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28
Q

It is important to differentiate generalized absence seizures from __ as the patient may be __.

A
  1. Complex partial seizures/ Focal onset seizures with dyscognitive features
  2. prescribed the wrong medication
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29
Q

Absence seizures differ from Focal onset seizures with dyscognitive features as they (absence seizures) __.

A

Absence seizures are:

  1. no proceeding auras
  2. short duration (seconds, rather than minutes)
  3. begin and end abruptly
  4. Characteristic ‘3Hz spike waves’ in EEG
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30
Q

*What are the characteristics of a generalized atonic seizure?

A

Most severe: all postural tone suddenly lost, collapsing to the ground (drop attacks)
Short episode
Immediate recovery
(MSI)

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31
Q

Which patient group is most likely to present with generalized atonic seizures?

A

Any age
Always associated with diffuse cerebral damage and learning disability
Common in severe symptomatic epilepsies i.e. Lennox
Gastaut syndrome

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32
Q

A young patient was reported to frequently stare at teachers and classmates by the parents. What kind of seizure condition is likely?

A

Absence seizures (Generalized onset)

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33
Q

A young patient presents at the clinic and shows multiple injuries i.e. falls, burns. What kind of seizure condition is likely?

A

Atonic seizures (Generalized onset)

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34
Q

Which positive symptom in a seizure is often used as a surrogate for impaired awareness?

A

Urinary incontinence

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35
Q

Which positive symptom in a seizure may suggest GTC seizures?

A

Muscle soreness (due to high levels of motor activity)

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36
Q

When a patient presents with dyscognitive features, it is important to rule out __.

A

syncope (fainting possible due to block in O2 supply)

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37
Q

When a patient describes a moving tingling sensation in fingers, it is important to rule out __.

A

Transient ischaemic attack (TIA stroke)

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38
Q

Patients that present with seizure-like jerking without EEG abnormalities may in fact not have seizures but instead have __.

A

Psychogenic nonepileptic seizures

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39
Q

__ have many overlapping non-specific symptoms with seizures and should be ruled out.

A

Migraines

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40
Q

*An epileptiform EEG __ while a normal EEG __.

electro-encephalo-graphy (EEG)

A
  1. confirms diagnosis of seizures/epilepsy

2. does not exclude possibility of epilepsy

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41
Q

*What are limitations of EEG?

A
  1. Not all epileptic patients have abnormal EEG (false negative)
  2. Normal patients may have abnormal EEG (false positive)
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42
Q

*What is the purpose of an MRI with gadolinium in the context of epilepsy?

A

To rule out structural abnormalities (i.e. focal leisons)

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43
Q

Who should receive an MRI with gadolinium?

A

Adults
1st seizure
Focal neurological deficit
Suggestive of focal onset seizure

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44
Q

*Why would a patient undergo biochemical/toxicology testing?

A

To rule out electrolyte abnormalities

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45
Q

Although serum prolactin is correlated with seizure activity, it is not used routinely due to __.

A

considerable variability

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46
Q

__ tests should be raised following a GTC seizure event as it has good correlation.

A

Creatinine Kinase (CK)

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47
Q

How should we begin with pharmacotherapy workup for a patient presenting with their 1st ‘seizure’ event?

A
  1. Is it a Seizure?
  2. First?
  3. Provoked/Cause?
  4. Need for AED? (risk of recurrence and patient factors)
    (SFPCN)
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48
Q

The risk of seizure recurrence is increased if patients have: __, __, __, __.

A
  1. Epileptiform EEG
  2. Structural abnormalities (brain imaging)
  3. Prior brain insult (stroke/trauma)
  4. Nocturnal seizure
    (ESPN)
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49
Q

The risk of recurrence after 2 unprovoked seizures is __, which is also usually the point we advise patients to start AED treatment.

A

~70%

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50
Q

Individualizing the pharmacologicals for the patient should be based on __, __ and __.

A
  1. seizure type/epilepsy syndrome
  2. co-morbidities and co-medications
  3. Patient preference/lifestyle/job
    (SCP)
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51
Q

When rapid titration is required, i.e. acute treatment of Status epilepticus, the use of __ or __ would not be appropriate due to their slow titration

A

Lamotrigine

Topiramate

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52
Q

When seizure patients also complain of migraines, the use of __ or __ is suitable.

A

Topiramate

Valproate

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53
Q

When seizure patients have depression/anxiety, __ should be used with caution.

A

Levetiracetam

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54
Q

AEDs with many DDIs i.e. __ or __ should be avoided if the patient is on concurrent drugs that also have complex DDIs i.e. HIV tx/immunosuppressants)

A

Carbamazepine

Phenytoin

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55
Q

For female epileptic patients with childbearing potential, __ or __ are good options.

A

Levetiracetam/Lamotrigine

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56
Q

__ may cause speech/thinking retardation (cognitive impairment) especially when newly started, and may not be a suitable AED for patients mentally intensive careers.

A

Topiramate

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57
Q

When initiating AEDs, we should start patient on a __, appropriate AED. If Seizures continue with no drug SEs, we should __.

A
  1. low dose, 1st line

2. gradually increase AED dose

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58
Q

If seizures continue despite max doses, we should conduct __, __, __.

A

Diagnosis Review
Adherence Check
Appropriate drug Check
(DAA)

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59
Q

*When should we consider substitution of AEDs?

A

1st AED causes ADRs or
Not tolerated at low doses or
Not effective

60
Q

*When should we consider adding on of AEDs (combination therapy)?

A

1st AED tolerated but with a suboptimal response

61
Q

*Non-pharmacological options for seizure patients include: __

A

Ketogenic diet
Vagus nerve stimulation (VNS)
Responsive neurostimulator system (RNS)
Surgery

62
Q

*What are some psychosocial challenges faced by epileptic patients?

A 
Caregiver burden 
Employment
Driving prohibition
Social stigma
(CEDS)
63
Q

*What are some possible seizure triggers?

A 
Hyperventilation
Sensory stimuli (i.e. Photostimulation)
Drugs
Infection
Stress (Physical and emotional)
Hormonal changes
Electrolyte imbalance
Sleep deprivation
(HS DISHES)
64
Q

Hormonal changes are possible seizure triggers. They may occur during __, __, __.

A

time of menses, puberty, or pregnancy

65
Q

Drugs are possible seizure triggers. Examples include:

A

Theophylline, alcohol, high dose phenothiazines, antidepressants (especially bupropion), tramadol, carbapenems

66
Q

Electrolyte imbalance is a possible seizure trigger. Examples include:
Hyper/Hypo: __
Hypo: __

A

Hyper/Hypo: Na

Hypo: Ca, Mg, Glucose

67
Q

*If we observe a person having a seizure >5min, we should __.

A

Call 995 for an ambulance

68
Q

*If we observe a person having a seizure, __ would be appropriate.

A 
Easing person to floor in prone position
Place soft/flat under head
Clearing the area around the person
Loosening ties/items around neck to prevent choking
Remove spectacles 
Time the seizure
69
Q

*If we observe a person having a seizure that is turning blue with cyanosis, should we engage in CPR?

A

No. CPR should only be initiated if the person collapses (i.e. no jerking but no breathing either)

70
Q

*What are the treatment options for New onset, Focal onset epilepsy?

A 
Levetiracetam (ILAE Level A)
Phenytoin (ILAE Level A)
Carbamazepine (ILAE Level A)
Valproate (ILAE Level B)
Topiramate
Lamotrigine (ILAE Level A, elderly)
Gabapentin (ILAE Level A, elderly)
(LPCVT LG)
71
Q

*What are the treatment options for New onset, Generalized onset epilepsy?

A

Topiramate
Lamotrigine
Valproate
(TLV)

72
Q

What are the possible treatment add-on options for refractory, Focal onset epilepsy?

A 
Clobazam
Lacosamide
Pregabalin
Perampanel
Any other new onset agent
(CLP P)
73
Q

*What are the treatment add-on options for refractory, Generalized onset epilepsy?

A

Clobazam
Levetiracetam
Any other new onset agent

74
Q

What are good treatment options for an elderly patient with New onset, Focal onset epilepsy? (assuming no other co-morbidities)

A

Gabapentin

Lamotrigine

75
Q

The majority of AEDs work on the voltage gated Na channels. __ has a special MOA as it acts on SV2A (glutamate) while __ works on the AMPA receptor (Na) Other AEDs i.e. __ work on the GABA receptor (Cl) as well.

SV2A - synaptic vesicle glycoprotein 2A

A
  1. Keppra (Levetiracetam)
  2. Perampanel
  3. Phenytoin
76
Q

What is the usual maintenance dose for Phenytoin?

A

300-400mg/day (or 5-7mg/kg/day)

77
Q

What is the usual maintenance and Max dose for Sodium valproate?

A

600-2000mg/day (or 20-30 mg/kg/day)

Max: 60 mg/kg/day

78
Q

What is the usual maintenance dose for Carbamazepine?

A

800-1200mg/day

79
Q

What is the usual maintenance dose for phenobarbitone/phenobarbital?

A

60-180mg/day

80
Q

What is the usual maintenance dose for Lamotrigine?

A

100-200mg/day

81
Q

What is the usual maintenance dose for Topiramate?

A

200-400mg/day

82
Q

What is the usual maintenance dose for Levetiracetam?

A

1000-3000mg/day

83
Q

*The 1st generation AEDs include: __, __, __ and __.

A

Carbamazepine
Phenytoin
Phenobarbitone/phenobarbital
Valproate

84
Q

*The 1st generation AEDs are all eliminated via __.

A

the hepatic route

85
Q

*The 1st generation AEDs are all __, which is relevant in the context of hypo-albuminemia or ESRF because of an __.

A
  1. highly protein bound

2. increased free fraction drug (increased effects)

86
Q
  • Of the 1st generation AEDs, all are potent inducers except __, which is a potent inhibitor
A

Valproate

87
Q

*Gabapentin and pregabalin are both mainly eliminated via __.

A

Renal route

88
Q

*Lamotrigine is mainly eliminated via __.

A

Hepatic route

89
Q

*Levetiracetam is mainly eliminated via __.

A

Hepatic route

90
Q

*Topiramate is mainly eliminated via __.

A

Renal route (30-55%)

91
Q

*Clobazam (3rd gen AED) is mainly eliminated via __.

A

Renal route

92
Q

*Among the 2nd gen AEDs, __ has few interactions while __ has dose-dependent interactions.

A
  1. Lamotrigine

2. Topiramate

93
Q

*Among the 2nd gen AEDs, __ has significant (55%) protein binding while __ has a low level (15%) of protein binding.

A
  1. Lamotrigine

2. Topiramate

94
Q

What are the key times to note when it comes to a patient taking potent CYP inducer/inhibitor?

A

During initiation and discontinuation

95
Q

*What are some drugs that may have DDIs with AEDs in general?

A 
Chemotherapy agents 
Antidepressants and antipsychotics
Immunosuppressants
Antiretroviral (i.e. HIV) medications
(CAIA)
96
Q

*Potent Enzyme inducing AEDs affect the reproductive hormones which would affect the patient’s __. We can also expect a similar effect on __ drugs that the patient takes.

A
  1. sexual function

2. oral-contraceptives

97
Q

*In the long term, AEDs may have effects on __ health and may affect __ risk

A
  1. bone

2. vascular

98
Q

*Phenytoin has good bioavailability and complete absorption. However, its absorption is reduced when given at __. Therefore, we should __.

A
  1. doses of >400mg

2. limit dose per setting to 400mg

99
Q

__’s absorption is reduced by NGT and feeds interaction. We should space out 1-2 hours between feeds and dosing.

A

Phenytoin

100
Q

*There is a need to correct for __ when administering phenytoin for a patient __.

A
  1. albumin level

2. with albumin <40g/L

101
Q

*__ can be displaced from albumin by endogenous compounds and other drugs.

A

Valproate

102
Q

__ exhibits saturable protein binding. This has implications when interpreting drug levels for patients with hypoalbuminemia.

(Free fraction increases linearly along with exponential increase in total drug level)

A

Valproate

103
Q

__ has an active metabolite and the parent drug levels may not fully reflect the clinical situation. It may be necessary to let patients return to baseline before re-initiating the drug to account for the active metabolite.

A

Carbamazepine

104
Q

*Carbamazepine undergoes CYP3A4 autoinduction increasing its clearance and decreasing its half-life over time. Maximal autoinduction occurs __. The clinical implication is __, which would reduce risk of SEs (i.e. ataxia).

A
  1. 2-3wks post drug initiation

2. avoid initiating target maintenance dose, instead start low and gradually increase over initial few weeks.

105
Q

*Concentration dependent CNS SEs of AEDs may include:

A 
Dizziness
Fatigue
Visual disturbances (usually double --/blurred vision)
Ataxia
Nystagmus
Somnolence
(DF VANS)
106
Q

*Carbamazepine and valproate may cause GI SEs such as: __

A

N/V

107
Q

*Levetiracetam may cause psychiatric SEs such as: __. We should pre-empt the patients and caregivers.

A

Behavioral disturbances i.e. irritability and aggression

108
Q

*Topiramate may cause cognitive SEs such as: __

A

Reduced speech fluency

109
Q

*Concentration dependent effects are particularly common during __ but patients may develop __.

A
  1. initiation

2. tolerance

110
Q

__ may reduce risk of conc-dependent SEs but also reduces adherence.

A

Splitting daily doses into smaller doses

111
Q

__ may reduce risk of conc dependent SEs only if the patients do not have day-time pre-dominant seizures.

A

Administering the largest AED dose at bedtime

112
Q

__ is a good option to reduce risk of conc dependent SEs as it results in flatter peaks.

A

Sustained release preparation

113
Q

*Gingival hyperplasia may be observed in almost half of all patients receiving chronic __ therapy

A

phenytoin

114
Q

*Hirsutism is commonly observed in children and young adults on chronic __ therapy. Facial hirsutism may affect up to 30% of __.

A
  1. phenytoin

2. young females

115
Q

*Alopecia occurs in 2-12% of patients receiving __.

A

sodium valproate

116
Q

*Due to cosmetic concerns, we avoid starting newly diagnosed epilepsy patients on __ and __. Patients should be made aware of the SEs and alternative options.

A

Phenytoin and Valproate

117
Q

*Encephalopathy is most commonly associated with prolonged __ treatment at high doses ( e.g. cerebellar atrophy). It may also occur with __.

A
  1. phenytoin

2. phenobarbitone

118
Q

*Peripheral neuropathy occurs in 8.5-18% of patients experience sensory loss after long term __ treatment at high doses. May or may not improve with decrease in AED dose. May respond with folate supplementation. Also associated with __ and __.

A
  1. phenytoin
  2. carbamazepine
  3. phenobarbitone
119
Q

*Increased weight gain is often associated with __. Gradually reverses spontaneously with discontinuation of treatment.

A

sodium valproate

120
Q

*Anorexia and weight loss is associated with __ and felbamate. It is reversible with discontinuation of drug. In fact, __ has been used as a weight loss agent.

A

topiramate

121
Q

*Osteomalacia is attributed to hepatic metabolism of vitamin D and/or inhibition of calcium absorption. Often associated with __, __ and __ (hepatic enzyme inducers).

A
  1. phenytoin
  2. phenobarbitone
  3. carbamazepine
122
Q

*Neonatal congenital defects are associated with __, __, __. Also, __may cause cognition issues for the fetus.

A

phenytoin, phenobarbitone, topiramate

Valproate

123
Q

*Isolated cases of blood dyscrasias are associated with __.

A

nearly all AEDs

124
Q

*__ is Rare (<1%) and occurs predominantly in patients receiving phenytoin. It is also associated with carbamazepine and phenobarbitone

A

Megaloblastic anaemia

125
Q

*__ has been associated with AED use. There should be no changes to ongoing therapy without first discussing with physician. Closer monitoring of symptoms is warranted. Compared to __, the risk of __ is significantly worse.

A
  1. Suicidal ideation

2. stopping AEDs or refusing to start AEDs

126
Q

There is a strong association between carriage of HLA B*1502 and risk of __. This is relevant for Han Chinese and other Asian ethnic grps e.g. Malays, Indians, Thais).

A

CBZ induced SJS/TEN

127
Q

Current clinical guidelines recommend HLA B1502 genotyping prior to starting __.

A

carbamazepine

128
Q

If patients are HLA B1502 positive, avoid __ and __.

A

carbamazepine and phenytoin

129
Q

HLA B*1502 genotyping prior to starting lamotrigine and phenytoin is not __/__/__.

A

not warranted
not cost effective
not well associated

130
Q

*Risk of serious cutaneous reaction is for Lamotrigine higher with __, __ and concomitant __.

A
  1. high starting doses
  2. rapid dose escalation
  3. valproate
131
Q

*To reduce risk of Lamotrigine induced SJS/TEN, slow titration is warranted. with the ‘slowest’ titration if patient is on concomitant __ and the ‘fastest’ titration if patient is on concomitant __.

A
  1. valproate (inhibitors)

2. CBZ/Ph/Pbt (inducers)

132
Q

State the dosing schedule for Lamotrigine if the patient is also on Valproate.
Wk 1-2: __
Wk 3-4: __
Wk 5-maintenance: increase by __
Usual maintenance dose: __, 100-400mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses)

A

Wk 1-2: 25mg every other day
Wk 3-4: 25mg/day
Wk 5-maintenance: 25-50mg/1-2wk
Usual maintenance dose: 100-200mg/day

133
Q 
State the dosing schedule for Lamotrigine if the patient is not taking concomitant inducers/inhibitors. 
Wk 1-2: \_\_
Wk 3-4: \_\_
Wk 5-maintenance: increase by \_\_
Usual maintenance dose: \_\_
A

Wk 1-2: 25mg every day
Wk 3-4: 50mg/day
Wk 5-maintenance: 50mg/1-2wk
Usual maintenance dose: 225-375mg/day (in 2 divided doses)

134
Q 
State the dosing schedule for Lamotrigine if the patient is taking concomitant inducers i.e. CBZ/Ph/Pbt. 
Wk 1-2: \_\_
Wk 3-4: \_\_
Wk 5-maintenance: increase by \_\_
Usual maintenance dose: \_\_
A

Wk 1-2: 50mg every day
Wk 3-4: 100mg/day (in 2 divided doses)
Wk 5-maintenance: 100mg/1-2wk
Usual maintenance dose: 300-500mg/day (in 2 divided doses)

135
Q

*Cross sensitivity for skin reactions have been associated with __.

A

AEDs with aromatic ring structures

136
Q

AEDs with aromatic ring structures include: Oxcarbazepine, __, __, __ and __.

A

Cbz
Lamo
Ph
Pbt

137
Q

AEDs WITHOUT aromatic ring structures include: __, __, __ and __.

A 
Levetiracetam
Gabapentin
Valproate
Topiramate 
(LGVT)
138
Q

*A lack of efficacy in AEDs may be due to: __, __, __, __ or changes in __/__.

A
  1. fast metabolizers
  2. Compliance issues
  3. inappropriate drug
  4. interactions (drug/food)
  5. change in physiology (age/pregnancy)
  6. change in formulation
139
Q

*Toxicity in AEDs may be due to __, __ or changes in __.

A
  1. slow metabolizers
  2. interactions (drug/food)
  3. change in physiology (liver/renal)
140
Q

The population derived reference ranges are
__: 10-20 mg/L
Valproate: __ mg/L
__: 4-12 mg/L
Phenobarbitone: __ mg/L
But we should always treat the patient and NOT the level.

A
  1. Phenytoin
  2. 50-100
  3. Carbamazepine
  4. 15-40
141
Q

*Oral contraceptives may lower __ concentrations, resulting in breakthrough seizures.

A

Lamotrigine

142
Q

*A patient is concerned regarding her AED drugs and breastfeeding the baby. What is your response?

A

Taking anti epileptic drugs is not an absolute contraindication to breastfeeding.
All breastfeeding women on AED therapy should be encouraged to breastfeed

143
Q

*When a seizure lasts __, it is likely to be prolonged (status epilepticus). When a seizure lasts __, it may cause long term consequences.

A
  1. > 5min

2. >30min

144
Q

*The initial treatment for status epilepticus is __ with __ preferred.

A

Benzodiazepines

IM/SC (non-oral ROA)

145
Q

*As the initial treatment for status epilepticus is usually insufficient, treatment for the second therapy phase may include: __ / __ or __ if the previous 2 options are unavailable.

A

IV Valproate/IV Levetiracetam

IV Phenobarbital

Psychiatric Pharmacotherapy (5 decks)

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