Phar 442 - Anti-Epileptic Drugs

Front 1

What is the definition of "personalized medicine"?

Back 1

The tailoring of medical treatments to the individual characteristics, needs and preferences of a patient during all stages if care, including prevention, diagnosis, treatment and following

Front 2

What are the considerations of Epilepsy treatment?

Back 2

1) Seizure Type

2) Epilepsy Syndrome

3) Efficacy

4) Cost

5) Pharmacokinetic profile

6) Adverse effects

7) Patient's related medical conditions

Front 3

What should an Antiepileptic Drug accomplish?

Back 3

Should decrease the frequency AND/OR decrease the severity of seizures in people with epilepsy

Front 4

"AED should prevent the development of epilepsy in individuals who have acquired a risk of seizures" True or False?

Back 4

FALSE

Front 5

What are the goals of AED therapy?

Back 5

Maximize quality of life by eliminating seizures (or dimish seizure frequency) while minimizing adverse drug effects

Front 6

How often does drug resistant epilepsy occur?

Back 6

Occurs in 40-60% of epilepsy patients

Front 7

What is the definition of "Drug Resistant Epilepsy"?

Back 7

Failure of adequate trials of two tolerated and appropiately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom for at least 1 year

Front 8

What are the AED specific variables that would impact AED selection?

Back 8

1) Seizure Type

2) Dose dependent SE

3) Idiosyncratic reactions

4) Chronic Toxicities

5) Teratogenicity

6) Carcinogenecity

6) Pharmacokinetics

7) Interaction Potential

8) Formulations

Front 9

What are the Patient specific variables that would impact AED selection?

Back 9

1) Genetic Background

2) Age

3) Gender

4) Comedications

5) Comorbidities

6) Insurance Coverage

7) Ability to swallow pills/tablets

Front 10

What are the Nation specific variables that would impact AED selection?

Back 10

1) AED availability

2) AED cost

3) Insurance Coverage

Front 11

Which of the AEDs are Broad Spectrum Agents used for Generalized seziures?

Back 11

1) Valproate 2) Felbamate

3) Lamotrigine 4) Topiramate

5) Zonisamide 6) Levetiracetam

7) Rufinamide 8) Vigabatrin

9) Clobazam

Front 12

Which of the AEDs are Narrow Spectrum Agents used for Partial Onset Seizures?

Back 12

1) Phenytoin 2) Carbamazepine

3) Oxcarbamazepine 4) Gabapentin

5) Pregabalin 6) Tiagabine

7) Lacosamide 8) Ezogabine

Front 13

Which of the AEDs used for Partial Onset Seizures can also be used for Generalized Tonic

Clonic seizures?

Back 13

1) Phenytoin 2) Carbamazepine

Front 14

Which of the AEDs are Narrow Spectrum Agents used for Absence Seizures?

Back 14

1) Ethosuxomide

Front 15

What are the general pharmacological targets of AED drugs?

Back 15

1) Increase inhibitory transmission

2) Decrease excitatory transmission

3) Regulate cellular excitability by blocking ionic flux across membranes

Front 16

"AEDs increase inhibitory transmission via ______ receptors"

Back 16

GABA

Front 17

How do AEDs increase inhibitory transmission?

Back 17

1) Enhancing GABA's postsynaptic inhibition

2) Blockade of GABA re-uptake into presynaptic terminal and glial cells

3) Blockade of GABA transaminase in terminals and glial cells

Front 18

What is the difference between GABA-A and GABA-B receptors?

Back 18

GABA-A: Ionotropic and principally Cl- channel.

GABA-B: Metabotropic and principally K+ channel

Front 19

Which AEDs increase inhibitory transmission?

Back 19

Barbiturates, Benzodiazepines, Tiagabine, Vigabatrin

Front 20

How do Barbituates increase inhibitory transmission?

Back 20

Act on GABA-A directly to modify Cl- channel opening by increasing open duration of the channel

Front 21

How do Benzodiazepines increase inhibitory transmission?

Back 21

Act on GABA-A directly to modify Cl- channel opening by increasing open frequency.

Front 22

How does Tiagabine increase inhibitory transmission?

Back 22

Inhibits GABA reuptake from synapses

Front 23

How does Vigabatrin increase inhibitory transmssion?

Back 23

Elevates GABA levels by irreversibly inhibiting its main catabolic enzyme; GABA-transaminase.

Front 24

"Gabapentin acts as a GABA receptor agonist" True or False?

Back 24

FALSE

Front 25

"AEDs decrease excitatory transmission via ______ receptors"

Back 25

Glutamate receptors

Front 26

What are the two principle categories of Glutamate receptors?

Back 26

i) Fast Synaptic Transmission/Ionotropic (AMPA, Kainate, NMDA)

ii) Slow Synaptic Transmission/Metabotropic (G-protein linked)

Front 27

What are the major concerns with Direct Glutamate receptor Antagonists?

Back 27

They are effective against experimental seizures BUT frequently cause Psychosis and other neuropsychiatric adverse effects clinically

Front 28

Which AEDs decrease excitatory transmission?

Back 28

Phenobarbital, Lamotrigine, Topiramate, Felbamate

Front 29

How does Phenobarbital decrease excitatory transmission?

Back 29

Inhibits the release of Glutamate from presynaptic terminal

Front 30

How does Lamotrigine decrease excitatory transmission?

Back 30

Inhibits the release of Glutamate from presynaptic terminal

Front 31

How does Topiramate decrease excitatory transmission?

Back 31

Blocks the AMPA receptor subtype on postsynaptic neurons which reduces Paroxysmal Depolarizing Shifts

Front 32

How does Felbamate decrease excitatory transmission?

Back 32

Blocks the NMDA neuromodulator "Glycine" from binding which reduces NMDA channel activity

Front 33

"AEDs regulate cellular excitability by ____________"

Back 33

Blocking ionic flux across cell membranes

Front 34

"Mutant ion channels are the principle genetic cause of Epilepsy" True or False?

Back 34

TRUE

Front 35

How do AEDs change voltage gated sodium channels to regulate cellular excitability?

Back 35

1) AEDs slow the rate of recovery from Na+ channel inactivation (decreasing high frequency burst discharges)

2) Prevent 'resurgent Sodium current"

Front 36

How do AEDs change voltage gated Calcium channels to regulate cellular excitability?

Back 36

Reduces calcium current flow across the membrane which modulates TC firing

Front 37

What is the similarity between Esclicarbazepine acetate (ESL) and Oxacarbazepine (OXC)?

Back 37

Both are metabolized to their active monohydroxy metabolite (Licarbazepine (i.e. 10-monohydroxyderivative))

Front 38

What are the types of drug interactions that can occur with AEDs?

Back 38

1) Addition of a new medication when an inducer/inhibitor is present

2) Addition of an inducer/inhibitor to an existing medication regimen

3) Removal of an inducer/inhibitor from chronic medication regimen

Front 39

Which AEDs are broad spectrum inducers?

Back 39

Carbamazepine, Phenytoin, Phenobarbital, Primidone

Front 40

Which AEDs are selective CYP3A inducers?

Back 40

Oxacarbazepine, Topiramate, Felbamate

Front 41

Which AEDs are selective CYP2C19 inducers?

Back 41

Felbamate, Topiramate, Oxcarbazepine

Front 42

Which AEDs inhibit the metabolism of other drugs?

Back 42

Valproate

Front 43

Which AEDs do not appear to be either inducers/inhibitors of CYP systems?

Back 43

1) Gabapentin 2) Zonisamide

3) Lamotrigine 4) Lacosamide

5) Pregabalin 6) Ezogabine

7) Tiagabine 8) Perampanel

9) Levetiracetam

Front 44

When can you consider discontinuing AED Therapy?

Back 44

i) Seizure free for >2 years

ii) have positive indicators for prognosis

Front 45

What positive inficators for prognosis of patients who are considering of withdrawal of AED therapy?

Back 45

1) Control achieved easily on one drug at low dose

2) No previous unsuccessful attempts at withdrawal

3) Normal neurological exam & EEG

4) Primary generalized seizures except JME

5) Consider relative risks/benefits

Front 46

Which of the AEDs are sodium channel bockers?

Back 46

1) Phenytoin 2) Carbamazepine

3) Oxacarbazepine 4) Eslicarbazepine acetate

5) Lamotrigine 6) Zonisamide

7) Rufinamide 8) Lacosamide

9) Topiramate 10) Valproate

11) Felbamate

Front 47

Which of the AEDs are Ca channel blockers?

Back 47

1) Zonisamide 2) Topiramate

3) Valproate 4) Felbamate

5) Gabapentin 6) Ethusuxamide

Front 48

Which of the AEDs block Ca channel by binding to α2-δ subtype?

Back 48

Gabapentin

Front 49

Which of the AEDs block low Threshold T-type Ca Channels?

Back 49

Ethusaxamide

Front 50

Which of the AEDs enhance the H-current?

Back 50

1) Lamotrigine

2) Gabapentin

Front 51

Which of the AEDs antagonize NMDA subtypes of Glutamte receptors?

Back 51

1) Phenytoin

2) Felbamate

3) Gabapentin

Front 52

Which of the AEDs antagonize AMPA subtypes of Glutamte receptors?

Back 52

1) Valproate

2) Perampanel

Front 53

Which of the AEDs antagonize Glycine subtypes of Glutamte receptors?

Back 53

1) Phenytoin

2) Gabapentin

Front 54

Which of the AEDs antagonize Kainate subtypes of Glutamte receptors?

Back 54

1) Lamotrigine

2) Topiramate

Front 55

Which of the AEDs enhances the effect of GABA?

Back 55

1) Carbamazepine 2) Oxacarbamezapine

3) Eslicarbazepine Acetate 4) Topiramate

5) Valproate 6) Felbamate

7) Barbiturates 8) Benzodiazepines

9) Tiagabine 10) Vigabatrin 11) Ezogabine

Front 56

Which of the AEDs enhances the effect of GABA at GABAa receptors?

Back 56

1) Barbiturates

2) Benzodiazepines

Front 57

Which of the AEDs intereferes with the re-uptake of GABA?

Back 57

1) Tiagabine

Front 58

Which of the AEDs inhibits transaminases which prevents breakdowns of GABA?

Back 58

1) Vigabatrin

Front 59

Which of the AEDs enhances the K channel?

Back 59

1) Oxcarbazepine

2) Eslicarbazepine Acetate

3) Ezogabine

Front 60

Which of the AEDs affects the KCNQ channel?

Back 60

Ezogabine

Front 61

Which of the AEDs inhibits Carbonic Anhydrase?

Back 61

1) Topiramate

2) Zonisamide (mild)

Front 62

What are the common adverse effects of AEDs?

Back 62

Dizziness, Fatigue, Ataxia, Diplopia

Front 63

Which of the AEDs cause Irritability, neuropsychiatric side effects?

Back 63

Levetiracetam, Ezogabine

Front 64

Which of the AEDs can cause "word finding difficulty"?

Back 64

Topiramate

Front 65

Which of the AEDs can cause Weight Loss/Anorexia?

Back 65

Topiramate, Zonisamide, Febomate

Front 66

Which of the AEDs can cause Weight Gain?

Back 66

Valproate, Carbamazepine, Gabapentin, Pregabalin

Front 67

Which of the AEDs can cause Rash?

Back 67

Phenytoin, Lamotrigine, Zonisamide, Carbamazepine

Front 68

Which of the AEDs can cause Renal Stones?

Back 68

Topiramate, Zonisamide

Front 69

Which of the AEDs can cause Anhydrosis/Heat Stroke?

Back 69

Topiramate, Zonisamide

Front 70

Which of the AEDs can cause Urinary Retention?

Back 70

Ezogabine

Front 71

Which of the AEDs can cause acute closed angle Glaucoma?

Back 71

Topiramate

Front 72

Which of the AEDs can cause Aplastic Anemia?

Back 72

Felbamate, Zonisamide, Valproate, Carbamazepine

Front 73

Which of the AEDs can cause Hyponatremia?

Back 73

Carbamazepine, Oxcarbezpine

Front 74

Which of the AEDs can cause Hepatic Failure?

Back 74

Valproate, Felbamate, Lamortrigine, Phenobarbital

Front 75

Which of the AEDs can cause Peripheral Vision Loss?

Back 75

Vigabatrin

Front 76

Which of the AEDs can cause Stevens Johnson Syndrome?

Back 76

Carbamazepine, Ethosuximide, Lamotrigine, Phenobarbital, Phenytoin

Front 77

SJS risk is higher with which group of patients?

Back 77

Patients with the HLA-B*1502 gene allele (which is higher in asians)

Front 78

Which of the AEDs can cause Osteomalacia/Osteoporosis?

Back 78

Carbamazepine, Barbiturates, Phenytoin, Oxcarbazepine, Valproate

Front 79

Which of the AEDs can cause Facial Coarsening?

Back 79

Phenytoin, Phenobarbital

Front 80

Which of the AEDs can cause Hirsuitism?

Back 80

Phenytoin, Phenobarbital

Front 81

Which of the AEDs can cause Gingival Hyperplasia?

Back 81

Phenytoin, Phenobarbital

Front 82

Which of the AEDs can cause contractures?

Back 82

Phenytoin, Phenobarbital

Front 83

Which of the AEDs can cause Polycystic Ovarian Syndrome?

Back 83

Valproic Acid

Front 84

Which of the AEDs can cause Cerebellar Degeneration?

Back 84

Phenytoin, Carbamazepine

Front 85

Which of the AEDs can cause Sexual Dysfunction?

Back 85

Phenytoin, Carbamezpine, Phenobarbital, Primidone

Front 86

Which of the AEDs carry an signficant risk of birth defects?

Back 86

Topiramate, Phenobarbital, Valproate,

Front 87

Which of the AEDs have a teratogenic risk lower than Valproate?

Back 87

Oxcarbazepine, Zonisamide, Gabapentin

Front 88

What are the "safest" AEDs for pregnancy?

Back 88

Lamotrigine, Levetiracetam, Phenytoin, Carbamzepine