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PR3136 > Treatment of Epilepsy ll > Flashcards

Treatment of Epilepsy ll Flashcards

1
Q

Factors influencing the choice of ASM (6)

A
  1. Seizure types
  2. Epilepsy syndrome
  3. Co-medication
  4. Comorbidity
  5. Patient’s lifestyle & preference
    - dosage form
    - dosing frequency
  6. National/institutional
    - guidelines
    - costs
    - availability
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2
Q

ASM requiring slow titration (2)

A
  1. Topiramate

2. Lamotrigine

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3
Q

ASM undergoing autoinduction

A

Carbamazepine

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4
Q

ASM for epilepsy with migraine (2)

A
  1. Topiramate

2. Valproate

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5
Q

ASM for epilepsy with depression/anxiety

A

Caution when using :

1. Levetiracetam

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6
Q

ASM for epilepsy with child-bearing potential (2)

A

Avoid Valproate, use :

  1. Lamotrigine
  2. Levetiracetam
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7
Q

Seizure recurrence risk

A 
1. 30% risk within the next 5 years, higher in first 2 years
Higher risk if :
- epileptiform abnormalities on EEG
- prior brain insult (eg stroke, trauma)
- structural abnormalities
- nocturnal seizures
  1. 70% risk after 2 unprovoked seizures at 4 years
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8
Q

ASM for focal onset epilepsy (7)

A

CPL2GVT

  1. Carbamazepine
  2. Levetiracetam
  3. Phenytoin
  4. Lamotrigine (elderly)
  5. Gabapentin (elderly)
  6. Valproate
  7. Topiramate
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9
Q

ASM for generalised tonic clonic epilepsy (4)

A

CVLaT

  1. Carbamazepine
  2. Lamotrigine
  3. Valproate
  4. Topiramate
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10
Q

1st gen ASM examples (4)

A
  1. Carbamazepine
  2. Valproate
  3. Phenytoin
  4. Phenobarbitone/Phenobarbital
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11
Q

2nd gen ASM examples (5)

A
  1. Lamotrigine
  2. Levetiracetam
  3. Topiramate
  4. Pregabalin
  5. Gabapentin
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12
Q

PK of 1st gen ASM

A
  • high protein binding
  • hepatic clearance
  • potential DDI
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13
Q

PK of 2nd gen ASM

A

Except lamotrigine

  • low protein binding
  • renal clearance
  • no DDI (except topiramate - dose dependent)
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14
Q

Lamotrigine unique PK

A

2nd gen ASM but

  • 55% protein binding
  • hepatic clearance
  • few DDI
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15
Q

DDI key targets (3)

A
  • UGT
  • CYP450
  • transporters
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16
Q

De-induction interactions

A
  • when an enzyme inducing ASM metabolism is discontinued
  • metabolic activity of the enzyme returns to baseline (reduced)
  • need to dose adjust the affected ASM drugs (reduce dose)
  • CPOE platforms or pharmacy system overlook this
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17
Q

Issues with enzyme-inducing ASM (DDI)

A
  • increase metabolism of victim drug
  • decrease serum conc of victim drug below therapeutic range
  • relapse/progression of disease
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18
Q

Phenytoin PK

A
  • IV, capsules and syrup
  • slow but complete absorption
  • bioavailability F=1 (reduced at doses >400mg/dose)
  • NGT & feeds interaction (space out 1-2h between feeds and dosing)
  • high albumin bound (90%)
  • Vd = 0.7 L/kg
  • correct phenytoin conc if albumin conc <40g/L
  • zero order / saturation kinetics
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19
Q

Phenytoin correction for albumin level

A

Only if albumin conc <4g/L

= C(observed) / [(x(alb/10)+0.1]

x = 0.1 (CrCl<10mL/min)
x = 0.2 (CrCl>=10mL/min)
alb = g/L
C = mg/L
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20
Q

Valproate PK

A
  • Injections, tablets and syrup
  • bioavailability F=1
  • high albumin bound (90-95%)
  • saturable protein binding within therapeutic range
  • competition for protein binding (warfarin, NSAIDs like aspirin)
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21
Q

Carbamazepine PK

A
  • tablets (immediate or controlled release)
  • bioavailability F=0.8
  • high albumin bound
  • active hepatic metabolites
  • autoinduction (occurs 2-3weeks later)
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22
Q

Dose-dependent ADR (4)

A
  1. CNS
    - somnolence
    - fatigue
    - dizziness
    - visual disturbances
    - nystagmus
    - ataxia
  2. GI
    - N/V
  3. Psychiatric
    - behavioural disturbances (levetiracetam)
  4. Cognition
    - speech fluency (topiramate)

May develop tolerance

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23
Q

Methods to overcome short-term dose-dependent ADR (4)

A
  1. Initiate therapy at low dose and titrate slowly
  2. Slow titration (avoid large dose changes)
  3. Monotherapy if possible (restrict the therapy to 1 drug only)
  4. Adjust dosing schedules
    - large dose at night
    - divide daily dose into more frequent smaller doses
    - use sustained release preparations
    - reduce total daily dose (if clinically safe)
24
Q

Idiopathic/hypersensitivity related ADR (6)

A
  1. Blood dyscrasia
  2. Hepatotoxicity
  3. Pancreatitis (valproate)
  4. Lupus-like reaction
  5. Exfoliative dermatitis
  6. TEN/SJS

Most likely to occur in first few months of therapy

25
Q

Methods to reduce risk of hypersensitivity reactions (3)

A
  1. Pharmacogenetic testing (carbamazepine HLAB*1502 genotyping)
  2. Follow dosing guidance (lamotrigine)
  3. Identify potential cross-reactivity reaction (aromatic ringed ASM)
26
Q

Pharmacogenetic testing

A
  • strong association between carriage of HLA-B*1502 gene and risk of carbamazepine induced hypersensitivity
  • Han chinese and other asians
  • test for HLA-B*1502 gene before initiating
  • positive : do not give carbamazepine & phenytoin
  • negative : can give but hypersensitivity might still occur
27
Q
  1. Follow dosing guidance for lamotrigine
A
  • risk of hypersensitivity if high dose, rapid dose escalation and concomitant use of valproate
  • 25mg EOD with valproate (inhibitor)
  • 25mg OD
  • 50mg OD with phenytoin, phenobarbital and carbamazepine (inducer)
28
Q

Reasons for TDM (5)

A
  1. Plasma ASM concentration correlate better than dose with clinic effects
  2. Assessment of therapeutic response on clinical grounds alone is difficult
  3. Not easy to recognise the signs of toxicity purely on clinical grounds
  4. Inter-individual variability for PK
  5. No laboratory markers for clinical efficacy or toxicity
29
Q

Indications for ASM TDM (4)

A
  1. Establish individual’s therapeutic range
  2. Lack of efficacy
  3. Loss of efficacy (breakthrough seizures)
  4. Toxicity
30
Q

Women of child-bearing age with OC

A
  • OC can decrease lamotrigine concentrations

- potent enzyme inducers of OC can render OC ineffective, need other contraceptives method

31
Q

Pregnancy and lactation

A
  • refer to specialist care for pre-conception counselling
  • not absolute CI for breastfeeding
  • all women are encouraged to breastfeed
32
Q

Stopping treatment (3)

A
  1. Minimum of 2 years without seizure
    - patients with increased risk of seizures have to wait longer than 2 years
  2. Age-dependent seizure and past applicable age
  3. Seizure free for 10 years and last 5 year without any medications

Balance between risk of stopping ASM and the benefits of stopping ASM

33
Q

Status epilepticus

A
  • failure of mechanism to terminate seizures

- failure of the initiation mechanisms leading to abnormally prolonged seizures

34
Q

Tonic Clonic Status Epilepticus

A
  • at least 5min of seizure

- 30min mark for long term consequences

35
Q

Status epilepticus treatment (0-5min)

A
  • ABCD
  • time seizure
  • assess oxygenation
  • ECG
  • hypocount
  • IV access for hematological, electrolyte and toxicology screen
36
Q

ABCD

A

airway
breathing
circulation
disability (neurologic exam)

37
Q

Status epilepticus treatment (5-20min) (3+2)

A
  • IM midazolam
  • IV lorazepam
  • IV diazepam
    OR
  • PR diazepam
  • IV phenobarbital
38
Q

Status epilepticus treatment (20-40min)

A
  • IV phenytoin
  • IV valproate
  • IV levetiracetam
    OR
  • IV phenobarbital
39
Q

Role of pharmacist

A
  1. Counsel patient on use of ASM
  2. Identify & address medication adherence issues
  3. Monitor efficacy & ADR
  4. Source drug info for other healthcare professionals
  5. Advocate best clinical practice in pharmacotherapy
  6. Take lead in generating new evidence that optimize patient outcomes
40
Q

MOA of Gabapentin and Pregabalin

A

alpha & delta subunits of Ca2+ channels

- inhibitory

41
Q

MOA of Levetiracetam

A

Synaptic Vesicle Glycoprotein 2A (SV2A)

42
Q

1st gen ASM CYP + UGT effect (4)

A

Induction (3)

  1. Carbamazepine
  2. Phenytoin
  3. Phenobarbital

Inhibition (1)
1. Valproate

UGT for all

43
Q

2nd gen ASM CYP effect

A

Topiramate

  • CYP3A moderate inducer
  • CYP2C19 moderate inhibitor
44
Q

2nd gen ASM no CYP effects (3)

A
  1. Gabapentin
  2. Pregabalin
  3. Levetiracetam
45
Q

Graph of saturable protein binding of Valproate (2)

A

As dose increases,

  1. Total conc increase in non-linear fashion
  2. Conc of unbound/free valproate increase linearly
46
Q

Can initiate patients on carbamazepine maintenance dose?

A

No as maintenance dose might be too high as induction of CYP enzymes will take 2-3 weeks

47
Q

Carbamazepine ADR (5)

A
  1. Nystagmus
  2. Diplopia
  3. Hyponatremia
  4. Aplastic anemia
  5. Neuropathy
48
Q

Phenytoin ADR (6)

A
  1. Nystagmus
  2. Diplopia
  3. Gingival hyperplasia
  4. Hirsutism
  5. Neuropathy
  6. Macrocystic anemia
49
Q

Valproate ADR (3)

A
  1. Weight gain
  2. Thrombocytopenia
  3. Alopecia
50
Q

Phenobarbitone ADR (2)

A
  1. Dysarthria

2. Nystagmus

51
Q

Levetiracetam ADR (3)

A
  1. Coordination difficulties
  2. Irritability
  3. Aggression
52
Q

Topiramate ADR (5)

A
  1. Cognitive dysfunction
  2. Weight loss
  3. Glaucoma
  4. Paresthesia
  5. Renal stones
53
Q

Pregabalin & Gabapentin ADR (2)

A
  1. Peripheral oedema

2. Weight gain

54
Q

Teratogenic ASMs (4)

A
  1. Valproate (cognition)
  2. Phenytoin
  3. Phenobarbitone
  4. Topiramate
55
Q

Suicidal ideation associated with ASM (3)

A
  • actual risk not established yet but seems v low
  • no change in therapy without discussing w physicians
  • close monitoring of symptoms

PR3136 (19 decks)

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