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3153 CNS - nat > ic4, 6, 7 (seizures, epilepsy) > Flashcards

ic4, 6, 7 (seizures, epilepsy) Flashcards

1
Q

What is a seizure?

A

Sudden (paroxysmal) event due to abnormal, hypersynchronous neuronal activity in brain

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2
Q

Acute seizure

Remote seizure

Unprovoked seizures

A

Acute: seizures from immediately recognisable stimulus eg. acute brain insult

Remote: seizures that occur longer than 1 week following a disorder which increases risk of epilepsy

Occurring beyond interval estimated for acute symptomatic seizures

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3
Q

Causes of seizures

A

Alcohol
Illegal drugs
Benzodiazepine withdrawal
Metabolic
Hypoglycemia
Hyponatremia
Hypomagnesemia
Hypocalcemia
Fever (pyrexia), CNS infection
Sleep deprivation
Hyperventilation
Photostimulation (bright lights)
Physical, emotional stress
Sensory stimuli eg. smells
Hormonal changes eg. during menses, puberty, pregnancy

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4
Q

Which ethnic group has highest prevalence of seizures?

A

Indians > Chinese > Malays

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5
Q

When is SUDEP most common in?

What happens in SUDEP

A

Highest in 20-40 yo

Convulsion → Apnoea → Asystole

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6
Q

Risk factors of SUDEP

A

seizures must be v bad, hence:
Frequent GTC
Nocturnal seizures
Lack of seizure freedom

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7
Q

Do drugs induce seizures?

A

More like lowering seizure threshold, increasing likelihood of seizures
Shift in excitatory / inhibitory balance

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8
Q

Drugs that induce seizures (5 points)

A

Antimicrobials (Beta lactams) eg. Cabapenems

Analgesics / Opioids eg. Meperidine, Tramadol

Antipsychotics eg. Clozapine

Immunosuppressants eg. Cyclosporine

Antidepressants / Smoking cessation eg. Bupropion

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9
Q

Pathophysiology of seizures (2 points)

A

Hyperexcitability and Hypersynchronisation

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10
Q

Definition of epilepsy

A

At least 2 unprovoked seizures occurring >24hrs apart

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11
Q

signs of seizure

A

Aura
Cyanosis
Loss of consciousness
Motor manifestations
Generalised stiffness of limb and body
Jerking of limbs
Tongue biting
Urinary incontinence
Post-ictal confusion
Muscle soreness

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12
Q

Examples of non-epileptic events

A

Psychogenic non-epileptic seizures (PNES)

Physiological non-epileptic events
Eg. migraine aura, TIA, panic attacks

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13
Q

What are some investigations to conduct for pts w epilepsy

A

Scalp encephalography

MRI with gadolinium

biochemical tests (electrolytes)

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14
Q

When is MRI with gadolinium indicated?

A

For pts with first seizure, focal neurologic deficits (problems with brain, nerve, spinal cord)

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15
Q

Risk factors for seizure recurrence

A

Epileptiform abnormalities in EEG
Brain trauma, stroke
Structural abnormality in brain imaging
Nocturnal seizure

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16
Q

Seizure first aid

A

Ease person to the floor
Turn person gently to one side
Clear area of anything hard or sharp
Put something soft eg. folded jacket under head
Remove spectacles
Loosen ties or anything around neck which constricts breathing
Time seizure, call 995 if more than 10 mins

DO NOT
Hold person down to stop movements
Put anything in their mouth
Give mouth to mouth breaths
Offer person water or food until fully alert

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17
Q

When should non pharm treatment be done in epilepsy?

A

Reserved for medical refractory epilepsy (when meds dont work)

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18
Q

4 types of non pharm for epilepsy

A

Ketogenic diet
Vagus nerve stimulation
RNS: Responsive neurostimulator system
Epileptic surgery

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19
Q

What is RNS?

When is responsive neurostimulator system indicated? (3 points)

A

Stimulator implanted in skull under the scalp, Leads implanted in brain

Continuously monitor electrical activity, detect specific patterns and deliver brief pulses of stimulation

Undergone diagnostic testing that localised 2 or less epileptogenic foci
Refractory to ≥ 2 antiepileptic medications
Frequent, disabling symptoms

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20
Q

What are the 1st gen ASM?

what do kind of metabolism?

A

Carbamazepine
Phenobarbital
Phenytoin
Sodium Valproate

Hepatic metabolism, hence can cause hepatotoxicity

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21
Q

Problems with 1st gen ASM

A

Poor water solubility
Extensive protein binding
Extensive CYP metabolism
Multiple DDI

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22
Q

2nd gen ASM

A

Lamotrigine
Levetiracetam
Topiramate

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23
Q

which asm are CYP inducers?

A

2C9, 2C19, 3A
(1st gen)
Carbamazepine
Phenobarbital
Phenytoin

(2nd gen)
Lamotrigine (UGT)
Topiramate (3A4)

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24
Q

which ASM are CYP inhibitors?

A

(1st gen)
Valproate (2C9)

(2nd gen)
Topiramate (2C19)

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25
Q

Which drugs classes will interact with CYP inducers?

A

Antidepressants, Antipsychotics
Immunosuppressive therapy
Antiretroviral
Chemo

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26
Q

What should be used for new onset Focal onset epilepsy?

A

Carbamazepine
Levetiracetam
Lamotrigine (elderly)

Valproate (B, 2nd line)

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27
Q

What should be used for new onset GTC?

A

Carbamazepine
Valproate
Lamotrigine
(same as focal onset but minus Leve)

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28
Q

What is the indication of Phenytoin?

Which drug has same indication

A

all types of seizure except absence seizure

same as Carbamazepine

29
Q

Bioavailability of Phenytoin?

What affects bioavailability of Phenytoin?

A

100%

Enteral feeds, space 2hrs apart

30
Q

Protein binding of Phenytoin

A

Highly albumin bound, affected by hypoalbuminemia (increase free Phenytoin)

Displaced by urea, Sodium Valproate

31
Q

Which drug displays zero order kinetics

What is capacity limited clearance

A

Phenytoin

as concentration increases, clearance decreases

32
Q

side effects of Phenytoin

A

Gingival hyperplasia

Hirsutism

Peripheral neuropathy
May not improve with lower dose
May respond to folate supplementation

33
Q

MOA of Carbamazepine

A

Block voltage dependent Na+ channel

34
Q

Which alleles associated with SJS / TEN in Carbamazepine?

A

HLA-B 1502, A 3101

1502 should do routine testing, 3101 dont need

35
Q

quirk about Carbamazepine

A

Undergoes autoinduction
Higher CL, shorter half life

Maximum autoinduction occurs 2-3 weeks after autoinduction

Do not start with desired maintenance dose, gradually increase dose over initial few weeks

36
Q

MOA of Sodium Valproate (two points)

A

1) Block voltage dependent Na+ and Ca2+ channels

2) Inhibit GABA transaminase (which breaks down GABA)
More GABA → more inhibitory CL- influx→ hyperpolarisation

37
Q

Indication of Sodium Valproate

A

All types of seizures, including absence seizures
Prophylaxis of migraine

38
Q

Which drug is a dual inducer and inhibitor?

A

Topiramate

39
Q

adverse effects of Sodium Valproate

A

Alopecia

Weight gain
Reverses when treatment discontinued

Nystagmus (involuntary eye movement)
Ataxia (no balance, coordination)
Slurred speech

40
Q

why do patient experience more AE with greater valproate dose?

A

as conc of valproate increases, protein binding is saturated, more free valproate in the body

41
Q

Which drugs are highly protein bound?

A

Phenytoin, Valproate

42
Q

MOA of Diazepam

A

Binds to regulatory site of GABA receptors
Improve influx of Cl- ions into cell → causing hyperpolarisation
+ Enhance binding of GABA to receptor

43
Q

serious adverse effect with Diazepam

How to treat?

A

Severe respiratory depression due to acute toxicity / overdose
Too much inhibition of brain activity → autonomic actions eg. breathing inhibited

Treatment: Flumazenil (benzodiazepine antagonist)
Binds to regulatory site of GABA receptor, displacing benzodiazepine
Lesser Cl- enters cell, cell is more depolarised and neuron is more excitable

44
Q

Why should Diazepam not be taken for long durations?

A

Can cause tolerance and dependence

Dependence: addiction, withdrawal effects eg. disturbed sleep, rebound anxiety, tremor, convulsions
Need to withdraw drug gradually

45
Q

MOA of Phenobarbital

A

Potentiates Cl- entry through GABA receptor into cell, but at different regulatory site than Benzodiazepines

Higher tendency to develop tolerance and dependence than Diazepam

46
Q

Which drug has the highest dependency risk?

A

Barbituate / Phenobarbital

47
Q

What is the indication of Phenobarbital?

A

in pediatric or neonatal patients (IV loading dose, IV / oral maintenance dose)

48
Q

Side effects of Levetiracetam

A

Agranulocytosis (immune deficiency)

Suicide, delirium

Dyskinesia (uncontrolled facial movements)

49
Q

MOA of Lamotrigine

A

1) block voltage gated Na+ channels

2) Inhibit release of Glutamate

(how to rmb: q similar to Valproate)

50
Q

Which medications block voltage gated sodium channels? (4 points)

A

Phenytoin, Sodium Valproate, Carbamazepine, Lamotrigine

51
Q

Indication of Lamotrigine

A

1) Partial and generalised seizures
2) Absence seizures

52
Q

Which drugs can treat absence seizures?

A

Valproate, Lamotrigine (how to rmb: absence, take LeaVe)

53
Q

Which drugs can cause agranulocytosis

A

Lamotrigine, Levetiracetam

Topiramate (as neutropenia)

54
Q

Which drugs can be used for Lennox Gastaut syndrome

A

Lamotrigine, Topiramate

55
Q

Indication of Topiramate

A

GTC, Lennox Gastaut

Migraine prophylaxis

56
Q

Which antiepileptics are indicated for migraine prophylaxis?

A

Topiramate, Vaproate

How to rmb: both are CYP inhibitors

57
Q

Which drug is affected by CYP metabolism?

Which drug is not affected by CYP inhibition?

A

Lamotrigine

Topiramate (as predominantly renal clearance)

58
Q

How to mitigate dose limited AE for ASM? (7 points)

A

Initiate at low dose, lowly increase dose if pt can tolerate
Avoid large dose changes
Restrict therapy to 1 drug only
Administer largest dose at bedtime
Divide daily dose into smaller doses
Use sustained release formulation
Reduce total daily dose if possible

59
Q

Which drugs cause hepatotoxicity?

A

1st gen ASM eg. Phenytoin, Valproate, Carbamazepine

60
Q

What genetic tests should be conducted for Carbamazepine?

Which other ASM should be avoided if found to be positive?

A

HLA-b*1502

Aromatic ASM
Phenytoin
Phenobarbital
Carbamazepine
Lamotrigine

61
Q

When should ASM be discontinued?

A

2 years without seizure

62
Q

When is seizure considered resolved (2 points)

A

1) Age dependent epilepsy syndrome but now is past applicable age

2) remain seizure free for last 10 years, with no seizure medications for last 5 years

63
Q

Which ASM make oral contraceptives ineffective?

Which contraceptives should be considered?

A

Potent inducers eg. Phenytoin, Carbamazepine

Use copper IUD, Depot injection, Higher dose of estrogen progestin pill + barrier method

64
Q

Which contraceptive affects the medication?

A

Lamotrigine, may have breakthrough seizures

65
Q

What ASM should be used for pregnancy?

A

Levetiracetam, Lamotrigine

Gabapentin (2nd line)

66
Q

What should men taking valproate do

A

Use contraception 3 months after stopping treatment

67
Q

How to treat status epilepticus? Treatment duration and drug

A

During 5-20 min phase
Benzodiazepine
IV Lorazepam 0.1mg/kg/dose, Max: 4mg/dose
IV Diazepam 0.2mg/kg/dose, Max 10mg/dose

During 20 min phase
IV Valproic acid 40mg/kg single dose, Max: 3g/dose
IV Levetiracetam 60mg/kg single dose, Max 4.5g/dose

68
Q

When should Phenytoin conc be calculated?

What is the formula?

A

When albumin < 40g/L

(check formula)

3153 CNS - nat (11 decks)

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