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Neurology 2 > Seizure/Epilepsy Drugs - Fitzpatrick > Flashcards

Seizure/Epilepsy Drugs - Fitzpatrick Flashcards

(66 cards)

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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
Zonisamide
New Limit EAA VGSC block AND VGCC block (T-type) Broad spectrum
26
Vigabatrin
New Enhance GABA GABA-T (metabolism) inhibition Simple/complex seizures (narrow spectrum)
27
Tiagabine
New Enhance GABA GABA re-uptake inhibitor Simple/complex seizures (narrow spectrum)
28
Lacosamide
``` New Limit EAA VGSC block SLOW INACTIVATION (activation gate) Best at PROLONGED stimuli Simple/complex seizures (narrow spectrum) ```
29
Clonazepam (Benzo)
Old Myotonic seizures and subcortical myoclonus Status epilepticus (IV or rectal)
30
2 ways to enhance GABA inhibitory transmission
1. Block GABA re-uptake or metabolism | 2. Potentiate GABA receptor Cl- currents
31
Phenobarbital vs. Benzodiazepine in GABA-A receptor agonism
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
Treating status epilepticus
1. Benzodiazepines (Diazepam or Lorazepam) - GABA-ergic to stop EEG bursts 2. Fosphenytoin (IF SEIZURE NOT STOPPED) - Na+ channel antagonist
33
Cause of status epilepticus
Abrupt withdrawal of AEDs
34
Diazepam vs. Lorazepam
Lorazepam - not cleared as quickly from circulation, thus can have longer-lasting effects than Valium
35
Status epilepticus + can't find IV vein
Clonazepam - rectal administration
36
Status epilepticus definition
Repeating seizures w/o regaining consciousness in between
37
Drugs w/ multiple mechanisms of action
Topirimate, Valproic acid
38
Valproic acid vs. Topirimate
Valproic acid (OLD) = VGSC + VGCC Topirimate (NEW) = VGSC + LGSC (glutamate receptor) + GABA-A receptor agonist
39
Gabapentin
Binds to VGCC | No drug interactions
40
Leviteracetam
Binds to PRE-SYNAPTIC glutamate vesicle Blunts glutamate release Well-tolerated, no CYP interaction
41
Ezogabine
``` Opens VGPC (potassium) Causes urinary retention ```
42
What is NOT used for absence seizures? Why?
Phenytoin and Carbamazepine Both of these are good for HIGH-FREQUENCY firing seizures, via blocking VGSC Treating absence seizures = blocking VGCC
43
Complications of phenytoin
Zero-order pharmacokinetics - Hard to adjust dose Induces CYP enzymes - Drug-drug interactions, etc.
44
Toxicities of phenytoin
GINGIVAL HYPERPLASIA Hirsutism Hypocalcemia Osteoporosis
45
How would patient present with carbamazepine toxicity?
Leukopenia/neutropenia, thrombocytopenia --> infections, bruising (APLASTIC ANEMIA)
46
Major cause of drug-drug interactions between AEDs
Hepatic CYP enzyme inductions
47
Osteoporosis in phenytoin/carbamazepine/phenobarbital/valproic acid CHRONIC USE toxicity
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
Patient on carbamazepine (or phenytoin) for 2 weeks starts to show recurrence of seizures. Explanation? Fix?
CYP induction --> reduced efficacy Increase dose
49
Carbamazepine + Oral Contraceptive
Increased CYP clearance of OC --> 4-fold OC failure rate --> risk for pregnancy
50
Carbamazepine + Oral Anti-coagulant (ex. warfarin)
Increased CYP clearance of drug --> risk for RAPID coagulation --> A/V thrombosis
51
Ginkgo supplements/nuts + anticonvulsants
CYP2C19 induction by ginkgo --> increased clearance of anticonvulsants
52
Fixing CYP drug-drug interactions
NEW AEDs
53
How do new AEDs prevent such CYP induction?
50% renal clearance | Drug structure does not allow for CYP conversion into TOXIC metabolites
54
10,11-CBZ epoxide
Toxic metabolite of carbamazepine
55
Patient on oxcarbazepine or carbamazepine complains of hyponatremia Why?
Increased responsiveess of collecting tubules to ADH (SIADH) --> increased water retention --> diluted blood --> hyponatremia
56
Gabapentin and Pregabalin
100% renal clearance (no CYP) | Renal insufficiency requires dose adjustment
57
Patient taking Lamotrigine presents with a rash Risk factor for this?
Stevens-Johnson syndrome = side effect - Life-threatening allergic reaction Taking Valproic acid as well
58
Lamotrigine and Valproic acid
Inhibit conjugation of other drugs by UGT enzymes --> accumulation of parent drug
59
Adverse effects: Levetiracetam
NONE
60
Adverse effects: Oxcarbazepine
Hyponatremia (elderly), rash
61
Adverse effects: Tiagabine
Stupor
62
Adverse effects: Topiramate
Nephrolithiasis (kidney stone) Open angle glaucoma Hypohidrosis
63
Adverse effects: Zonisamide
Rash Renal calculi Hypohidrosis
64
Carbamazepine warnings
``` Allergic reaction (S-J syndrome) Aplastic anemia ```
65
Lamotrigine warning
Allergic reaction (S-J syndrome)
66
Teratogenic drugs
Valproic acid Carbamazepine Phenytoin

Neurology 2 (22 decks)

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