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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?

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
Implication of drugs that undergo autoinduction
Do not start with desired maintenance dose at the first dose, but gradually increase over the initial few weeks
26
Idiosyncratic / hypersensitivity related side effects most likely occur in _____ of therapy
first few months of therapy
27
Peripheral neuropathy (side effect) may respond with ____ but may or may not improve with ____
folate supplementation; decrease in ASM dose
28
Recommendation for _____genotyping prior to starting carbamazepine (due to association with SJS/TEN)
HLA-B*1502
29
HLA-B*1502 positive – avoid ______
carbamazepine & phenytoin
30
What increases risk of serious cutaneous reaction in lamotrigine?
high starting doses, rapid dose escalation, concomitant valproate
31
Lamotrigine Dose titration in patients taking concomitant valproate
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
Lamotrigine Dose titration in patients NOT taking other ASMs (CBZ, VPA, phenytoin, phenobarbital)
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
Lamotrigine Dose titration in patients taking CBZ/PNT/PNB and NOT valproate
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
Hypothesis of mechanism by which ASMs induce skin reaction
- ASMs with an aromatic ring can form an arene-oxide intermediate – Become immunogenic through interactions with proteins or cellular macromolecules
35
Which ASM affects speech fluency
Topiramate
36
Phenytoin dosage forms
– Oral suspension (125mg/5ml): Phenytoin acid (100% phenytoin) – Capsules (30mg. 100mg) - IV Phenytoin sodium (92% phenytoin)
37
Valproate dosage form
o Injection (400mg/vial) o Enteric-coated tablet (200mg) o Sustained-released tablets (Chrono 200mg, 300mg, 500mg) o Syrup (200mg/5ml)
38
Carbamazepine dosage form
– Immediate-release tablets (200mg) – Controlled-release CR tablets (200mg, 400mg)
39
Ref range for CBZ
4-12 mg/L
40
Ref range for VPA
50-100mg/L
41
Ref range for PNT
10-20 mg/L
42
Ref range for PBB
15-40 mg/L
43
When is an epilepsy considered resolved
- 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
Effect of pregnancy on use of contraception
- Potent enzyme inducers may render OC ineffective, alternative methods required - For patients on lamotrigine, OC may lower lamotrigine concentrations, resulting in breakthrough seizures
45
Safer ASMs for pregnancy
Levetiracetam and lamotrigine
46
Valproate use in pregnancy could cause...
Serious developmental disorders and congenital malformations in babies
47
ASMs (apart from valproate) that could lead to incr risk of congenital malformations/ neurodevelopmental
Carbamazepine, phenobarbital, phenytoin and topiramate
48
Definition of status epilepticus
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
t1 for tonic-clonic SE
5 mins
50
t2 for tonic-clonic SE
30 mins
51
HLA-B*1502 testing for carbamazepine is relevant for ___
Relevant for Han Chinese and other Asian ethnic grps (e.g. Malays, Indians, Thais)

PR3153 (17 decks)

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