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PR3153 > IC7 > Flashcards

IC7 Flashcards

1
Q

How many ASM generations are there

A

3

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2
Q

Common 1st gen ASM

A
  • Carbamazepine (Tegretol)
  • Phenobarbitone/ phenobarbital
  • Phenytoin (Dilantin)
  • Sodium valproate (Epilim)
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3
Q

Common 2nd gen ASM

A
  • Lamotrigine (Lamictal)
  • Levetiracetam (Keppra)
  • Topiramate (Topamax)
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4
Q

Example of an excitatory neurotransmitter

A

Glutamate

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5
Q

Example of an inhibitory neurotransmitter

A

GABA

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6
Q

Preferred treatment for focal onset epilepsy in elderly

A

*Lamotrigine (ILAE Level A,- elderly) *Gabapentin (ILAE Level A- elderly)

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7
Q

1st line option for focal onset epilepsy

A

*Carbamazepine (ILAE Level A) *Levetiracetam (ILAE Level A)
*Phenytoin (ILAE Level A)

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8
Q

1st-line Treatment options for GTC

A

*Lamotrigine (ILAE Level C)
*Valproate (ILAE Level C)
*Carbamazepine (ILAE Level C)

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9
Q

Last-line for GTC

A

Levetiracetam

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10
Q

Levetiracetam route of elimination

A

66% renal

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11
Q

Route of elimination: Pregabalin & gabapentin

A

100% (GP); 90% (PGB) renal elimination

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12
Q

Topiramate route of elimination

A

30-55% renal

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13
Q

1st gen ASM: Potent Enzyme inducers

A

– Carbamazepine → CYP (1A2, 2C, 3A4) , UGTs
– Phenytoin → CYP (2C, 3A) , UGTs
– Phenobarbital/Primidone → CYP (1A, 2A6, 2B, 3A) , UGTs

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14
Q

1st gen ASM: Potent Enzyme inhibitor

A

Valproate → (CYP2C9, UGT)

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15
Q

2nd gen ASM: No effects on CYP

A

Gabapentin, Levetiracetam, Pregabalin

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16
Q

2nd gen ASM: Moderate inducer

A

Topiramate (CYP3A); significant when > 200mg

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17
Q

Phenytoin correction needed when there is ____

A

albumin < 40 g/L or renal impairment

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18
Q

Capacity-limited clearance meaning

A
  • Clearance is dependent on concentration
  • Clearance will decrease with increasing concentration
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19
Q

Which ASM has zero-order kinetics (non-linear)?

A

Phenytoin

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20
Q

Carbamazepine: when is maximal autoinduction?

A

Maximal autoinduction usually occurs 2- 3 weeks after dose initiation

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21
Q

Which ASM has saturable ptn-binding within therapeutic range?

A

Valproate

22
Q

Implication of saturable ptn-binding within therapeutic range:
- decreased/ increased protein binding at higher conc
- Lower/ Higher free fraction of drug with low alb

A

decreased; Higher

23
Q

Implication of zero-order kinetics

A

Unlike first-order kinetics, concentration increment is NOT proportional to dose increment

24
Q

Active metabolite of carbamazepine

A

Carbamazepine-10,11-epoxide

25
Q

Implication of drugs that undergo autoinduction

A

Do not start with desired maintenance dose at the first dose, but gradually increase over the initial few weeks

26
Q

Idiosyncratic / hypersensitivity related side effects most likely occur in _____ of therapy

A

first few months of therapy

27
Q

Peripheral neuropathy (side effect) may respond with ____ but may or may not improve with ____

A

folate supplementation; decrease in ASM dose

28
Q

Recommendation for _____genotyping prior to starting carbamazepine (due to association with SJS/TEN)

A

HLA-B*1502

29
Q

HLA-B*1502 positive – avoid ______

A

carbamazepine & phenytoin

30
Q

What increases risk of serious cutaneous reaction in lamotrigine?

A

high starting doses, rapid dose escalation, concomitant valproate

31
Q

Lamotrigine Dose titration in patients taking concomitant valproate

A

Week 1 -2: Initiate 25mg every other day
Week 3-4: 25 mg/day
Week 5 onward: Incr 25-50 mg/day every 1 to 2 weeks
Usual maintenance dose:
100-200 mg / day with valproate alone
100-400mg/day with valproate and other drugs inducing glucuronidation
(in 1 or 2 divided doses)

32
Q

Lamotrigine Dose titration in patients NOT taking other ASMs (CBZ, VPA, phenytoin, phenobarbital)

A

Week 1 -2: Initiate 25mg /day
Week 3-4: 50mg/day
Week 5 onward: Incr 50 mg/day every 1 to 2 weeks
Usual maintenance dose:
225-375mg/day in 2 divided doses

33
Q

Lamotrigine Dose titration in patients taking CBZ/PNT/PNB and NOT valproate

A

Week 1 -2: Initiate 50mg/day
Week 3-4: 100mg/day in 2 divided doses
Week 5 onward: Incr 100 mg/day every 1 to 2 weeks
Usual maintenance dose:
300-500mg / day in 2 divided doses

34
Q

Hypothesis of mechanism by which ASMs induce skin reaction

A
  • ASMs with an aromatic ring can form an arene-oxide intermediate
    – Become immunogenic through interactions with proteins or cellular macromolecules
35
Q

Which ASM affects speech fluency

A

Topiramate

36
Q

Phenytoin dosage forms

A

– Oral suspension (125mg/5ml):
Phenytoin acid (100% phenytoin)
– Capsules (30mg. 100mg)
- IV Phenytoin sodium (92% phenytoin)

37
Q

Valproate dosage form

A

o Injection (400mg/vial)
o Enteric-coated tablet (200mg)
o Sustained-released tablets (Chrono 200mg, 300mg, 500mg)
o Syrup (200mg/5ml)

38
Q

Carbamazepine dosage form

A

– Immediate-release tablets (200mg)
– Controlled-release CR tablets (200mg, 400mg)

39
Q

Ref range for CBZ

A

4-12 mg/L

40
Q

Ref range for VPA

A

50-100mg/L

41
Q

Ref range for PNT

A

10-20 mg/L

42
Q

Ref range for PBB

A

15-40 mg/L

43
Q

When is an epilepsy considered resolved

A
  • individuals who had an age-dependent epilepsy syndrome but are now past the applicable age
    OR
  • remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years.
44
Q

Effect of pregnancy on use of contraception

A
  • Potent enzyme inducers may render OC ineffective, alternative methods required
  • For patients on lamotrigine, OC may lower lamotrigine concentrations, resulting in breakthrough seizures
45
Q

Safer ASMs for pregnancy

A

Levetiracetam and lamotrigine

46
Q

Valproate use in pregnancy could cause…

A

Serious developmental disorders and congenital malformations in babies

47
Q

ASMs (apart from valproate) that could lead to incr risk of congenital malformations/ neurodevelopmental

A

Carbamazepine, phenobarbital, phenytoin and topiramate

48
Q

Definition of status epilepticus

A

A condition that results from either
1) failure of mechanisms responsible for seizure termination or
2) initiation of mechanisms which lead to abnormally prolonged seizures.

49
Q

t1 for tonic-clonic SE

A

5 mins

50
Q

t2 for tonic-clonic SE

A

30 mins

51
Q

HLA-B*1502 testing for carbamazepine is relevant for ___

A

Relevant for Han Chinese and other Asian ethnic grps (e.g. Malays, Indians, Thais)

PR3153 (17 decks)

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