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Neurology 2 > Seizure/Epilepsy Drugs - Fitzpatrick > Flashcards

Seizure/Epilepsy Drugs - Fitzpatrick Flashcards

1
Q

Absence seizures Tx

A

Ethosuximide

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2
Q

Atonic, myoclonic, clonic seizures Tx

A

Benzodiazepines, clonazepam

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3
Q

Tonic-clonic seisures Tx

A

Carbamazepine, Phenytoin, Phenobarbitol

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4
Q

Partial onset simple/complex seizures Tx

A

Gabapentin, Prebabalin, Oxcarbazepine, Lacosamide, Tiagabine, Vigabatrin, Ezogabin

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5
Q

Partial onset tonic-clonic seizures Tx

A

Carbamazepine, Phenytoin, Phenobarbital

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6
Q

Broad specturm (together or alone)

A

Valproate, Lamotrigine, Topirimate, Levetiracetam, Zonisamide

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7
Q

Newer drugs

A

All Simple/Complex partial onset + All broad spectrum EXCEPT Valproate

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8
Q

Good thing about newer drugs

A

Not hepatically metabolized, less side effects

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9
Q

How to use simple/complex narrow spectrum

A

Will each other or with older drug

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10
Q

Which ones are narrow spectrum?

A

Tonic/clonic (general onset) + Simple/complex (partial onset)

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11
Q

2 main things to antagonize for seizures

A
  1. Voltage-gated Na+ channels

2. Low-threshold (T-type) Ca++ channels

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12
Q

Absence seizures (Tx target)

A

Low-threshold (T-type) Ca++ channels

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13
Q

Drugs used to treat epilepsy target NT systems to do what 2 things?

A
  1. Slow glutamate (EAA) transmission

2. Enhance GABA (inhibitory) transmission

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14
Q

Phenytoin

Effect on cognitive function?

A 
Old
Limit EAA
VGSC block
Fast inactivation (inactivation gate)
Slow recovery from inactivation
Best at depolarize or high-frequency firing membranes
     - USE-DEPENDENT
ZERO-ORDER KINETICS - Hard to dose ∆
Induces CYP enzymes (drug interactions)
Tonic-clonic seizures (Narrow spectrum)

Minimal – cognition = low-frequency

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15
Q

Phenobarbital (Barbiturate)

A

Old
Enhance GABA
Like Benzodiazepines (Diazepam) BUT w/ dose-dependent lethality and side effects
DEPRESSION, sedation, lethal respiratory depression, abusive/addictive
Tonic-clonic seizures (Narrow spectrum)

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16
Q

Diazepam (Benzo)

A 
Old
Enhance GABA
Allosterically potentiates effects of GABA transmission
Lethal w/ alcohol
Myotonic, atonic, clonic seizures
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17
Q

Ethosuximide

A 
Old
Limit EAA
VGCC (Ca++) (T-type) block
Absence seizures
NON-SEDATING
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18
Q

Carbamazepine

A 
Old
Limit EAA
VGSC block
Fast inactivation (inactivation gate)
Faster binding than Phenytoin, better at high-freq. firing
     - USE-DEPENDENT
Tonic-clonic seizures (narrow spectrum)
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19
Q

Valproate

A 
Old
BOTH (limit EAA and enhance GABA)
VGSC + VGCC
Broad spectrum
Side effects = weight gain, tremor, hair loss, lethargy, neural tube defects (mothers)
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20
Q

“Broad-spectrum” definition

A

Limits EAA AND enhances GABA

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21
Q

Lamotrigine

A 
New
Limit EAA
VGSC block
Fast inactivation (inactivation gate)
Also acts on N and P-type VGCC (Ca++) in cortex
Broad spectrum
Toxic = STEVENS-JOHNSON SYNDROME
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22
Q

Topirimate

A 
New
BOTH (limit EAA and enhace GABA)
VGSC + LGSC (AMPA/glutamate receptor)
Potentiates GABA-A receptors
Broad spectrum
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23
Q

Fosphenytoin

A

Limit EAA

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24
Q

Oxcarbazepine

A 
New
Limit EAA
VGSC block
Fast inactivation (inactivation gate)
Simple/complex seizures (narrow spectrum)
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25
Q

Zonisamide

A

New
Limit EAA
VGSC block AND VGCC block (T-type)
Broad spectrum

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26
Q

Vigabatrin

A

New
Enhance GABA
GABA-T (metabolism) inhibition
Simple/complex seizures (narrow spectrum)

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27
Q

Tiagabine

A

New
Enhance GABA
GABA re-uptake inhibitor
Simple/complex seizures (narrow spectrum)

28
Q

Lacosamide

A 
New
Limit EAA
VGSC block
SLOW INACTIVATION (activation gate)
Best at PROLONGED stimuli
Simple/complex seizures (narrow spectrum)
29
Q

Clonazepam (Benzo)

A

Old
Myotonic seizures and subcortical myoclonus
Status epilepticus (IV or rectal)

30
Q

2 ways to enhance GABA inhibitory transmission

A
  1. Block GABA re-uptake or metabolism

2. Potentiate GABA receptor Cl- currents

31
Q

Phenobarbital vs. Benzodiazepine in GABA-A receptor agonism

A

Pheno - GABA-independent, can easily overdose and cause coma and respiratory depression

Benzo - GABA-dependent, much more difficult to lethally OD, will never reach respiratory depression state

32
Q

Treating status epilepticus

A
  1. Benzodiazepines (Diazepam or Lorazepam)
    • GABA-ergic to stop EEG bursts
  2. Fosphenytoin (IF SEIZURE NOT STOPPED)
    • Na+ channel antagonist
33
Q

Cause of status epilepticus

A

Abrupt withdrawal of AEDs

34
Q

Diazepam vs. Lorazepam

A

Lorazepam - not cleared as quickly from circulation, thus can have longer-lasting effects than Valium

35
Q

Status epilepticus + can’t find IV vein

A

Clonazepam - rectal administration

36
Q

Status epilepticus definition

A

Repeating seizures w/o regaining consciousness in between

37
Q

Drugs w/ multiple mechanisms of action

A

Topirimate, Valproic acid

38
Q

Valproic acid vs. Topirimate

A

Valproic acid (OLD) = VGSC + VGCC

Topirimate (NEW) = VGSC + LGSC (glutamate receptor) + GABA-A receptor agonist

39
Q

Gabapentin

A

Binds to VGCC

No drug interactions

40
Q

Leviteracetam

A

Binds to PRE-SYNAPTIC glutamate vesicle
Blunts glutamate release
Well-tolerated, no CYP interaction

41
Q

Ezogabine

A 
Opens VGPC (potassium)
Causes urinary retention
42
Q

What is NOT used for absence seizures?

Why?

A

Phenytoin and Carbamazepine

Both of these are good for HIGH-FREQUENCY firing seizures, via blocking VGSC

Treating absence seizures = blocking VGCC

43
Q

Complications of phenytoin

A

Zero-order pharmacokinetics
- Hard to adjust dose
Induces CYP enzymes
- Drug-drug interactions, etc.

44
Q

Toxicities of phenytoin

A

GINGIVAL HYPERPLASIA
Hirsutism
Hypocalcemia
Osteoporosis

45
Q

How would patient present with carbamazepine toxicity?

A

Leukopenia/neutropenia, thrombocytopenia –> infections, bruising (APLASTIC ANEMIA)

46
Q

Major cause of drug-drug interactions between AEDs

A

Hepatic CYP enzyme inductions

47
Q

Osteoporosis in phenytoin/carbamazepine/phenobarbital/valproic acid CHRONIC USE toxicity

A
  1. P450-induced vitamin D catabolism
  2. Reduced vitamin D levels
  3. Decreased absorption of intestinal Ca++
  4. Compensatory PTH release
  5. PTH –> bone demineralization
48
Q

Patient on carbamazepine (or phenytoin) for 2 weeks starts to show recurrence of seizures. Explanation?

Fix?

A

CYP induction –> reduced efficacy

Increase dose

49
Q

Carbamazepine + Oral Contraceptive

A

Increased CYP clearance of OC –> 4-fold OC failure rate –> risk for pregnancy

50
Q

Carbamazepine + Oral Anti-coagulant (ex. warfarin)

A

Increased CYP clearance of drug –> risk for RAPID coagulation –> A/V thrombosis

51
Q

Ginkgo supplements/nuts + anticonvulsants

A

CYP2C19 induction by ginkgo –> increased clearance of anticonvulsants

52
Q

Fixing CYP drug-drug interactions

A

NEW AEDs

53
Q

How do new AEDs prevent such CYP induction?

A

50% renal clearance

Drug structure does not allow for CYP conversion into TOXIC metabolites

54
Q

10,11-CBZ epoxide

A

Toxic metabolite of carbamazepine

55
Q

Patient on oxcarbazepine or carbamazepine complains of hyponatremia

Why?

A

Increased responsiveess of collecting tubules to ADH (SIADH) –> increased water retention –> diluted blood –> hyponatremia

56
Q

Gabapentin and Pregabalin

A

100% renal clearance (no CYP)

Renal insufficiency requires dose adjustment

57
Q

Patient taking Lamotrigine presents with a rash

Risk factor for this?

A

Stevens-Johnson syndrome = side effect
- Life-threatening allergic reaction

Taking Valproic acid as well

58
Q

Lamotrigine and Valproic acid

A

Inhibit conjugation of other drugs by UGT enzymes –> accumulation of parent drug

59
Q

Adverse effects:

Levetiracetam

A

NONE

60
Q

Adverse effects:

Oxcarbazepine

A

Hyponatremia (elderly), rash

61
Q

Adverse effects:

Tiagabine

A

Stupor

62
Q

Adverse effects:

Topiramate

A

Nephrolithiasis (kidney stone)
Open angle glaucoma
Hypohidrosis

63
Q

Adverse effects:

Zonisamide

A

Rash
Renal calculi
Hypohidrosis

64
Q

Carbamazepine warnings

A 
Allergic reaction (S-J syndrome)
Aplastic anemia
65
Q

Lamotrigine warning

A

Allergic reaction (S-J syndrome)

66
Q

Teratogenic drugs

A

Valproic acid
Carbamazepine
Phenytoin

Neurology 2 (22 decks)

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