Pharm For Seizures And Epilepsy

Question 1

What drug is used for Generalized Onset Absence seizures?

Answer 1

Ethosuximide

Question 2

What drug is used for generalized onset myotonic, atonic, or clinic seizures?

Answer 2

Benzodiazepines (clonizapam has multiple forms of administration)

Question 3

What drugs are used to treat generalized onset tonic/clinic (grand mal) seizures?

Answer 3

Phenytoin, phenobarbital, carbamazepine (must start with partial onset)

Question 4

What drugs can be used for partial onset simple complex seizures?

Answer 4

Carbamazepine, gabapentin, lecosamide, oxcarbazepine, tigabine, vigabatrin, ezogabin.

Question 5

What are the broad spectrum drugs used to treat seizure activity?

Answer 5

Valproate, lemotrigine, topirmate, levetiracetam, zonisamide.

Question 6

What two structures do AED’s antagonize to decrease excitation?

Answer 6

1) Voltage-gated Na+ channels

2) Low-Threshold (t type) Ca2+ channels

Question 7

What drugs antagonize the voltage-gated Na+ channels on pre-synaptic neurons?

Answer 7

Phenytoin, carbamazepine, lamotrigine, oxcarbazepine, zonisamide.

Question 8

What drugs prolong the fast inactivation state of the Na+ channel?

Answer 8

Phenytoin, Carbamazepine, lamotrigine, oxcarbazepine

Question 9

What drug enhances the slow inactivation of voltage gated Na+ channels?

Answer 9

Lacosamide

Question 10

At what state can AED’s bind to the interior of the Na+ channel?

Answer 10

Activation gate must be open

Question 11

How does phenytoin and carbamazepine differ with their actions at the Na+ channel?

Answer 11

Phenytoin- most effective at depolarized potentials and high-frequency AP firing.

Carbamazepine- binds less effectively, but with much faster rate then phenytoin. More effective in blocking high-frequency AP firing.

Question 12

What is the MOA of Lamotrigine?

Answer 12

Similar to phenytoin and carbamazepine with the addition of N and P type voltage gated Ca2+ channels in cortical neurons.

Question 13

What is the MOA of Lacosamide?

Answer 13

• Stabilizes the slow-inactivated state.

- Used in the treatment of partial seizures.

Question 14

What are the defining features of absence seizures (petit mal)?

Answer 14

• 3Hz spike and wave activity of EEG.
• T-type Ca2+ channels are affected.
• Target cortex-thalamus oscillation.

Question 15

What is the drug off choice in treating absence petit mal seizures?

Answer 15

• Ethosuximide-> only used to treat this type!

- Non-Sedating

Question 16

If your patient does not respond to Ethosuximide in the treatment of their petit mal seizure, what is the next best drug to use?

Answer 16

Broad spectrum AED such as Valproate or lamotrigine. By definition they will affect the dysregulated channels.

Question 17

What is unique about the AED zonisamide?

Answer 17

Blocks voltage dependent Na+ channels and T-type calcium channels.

Question 18

What two mechanisms do AED’s use to augment Inhibition?

Answer 18

1) Block GABA re-uptake or metabolism

2) Potentiate GABAa receptor Cl- currents

Question 19

What drug inhibits GABA re-uptake?

Answer 19

Tiagabine

Question 20

What drug inhibits GABA metabolism, doesn’t allow the conversion of GABA-> glutamate to occur?

Answer 20

Vigabatrin

Question 21

What is the MOA of benzodiazepines?

Answer 21

Bind to GABAa causing an allosteric change that potentiates GABA binding allowing Cl- to enter the cell.

Question 22

What is the MOA of barbiturates?

Answer 22

Bind to a distinct and increase the duration of the Cl- channel opening

Question 23

What is the main difference between benzodiazepines and barbiturates?

Answer 23

Benzodiazepines are GABA dependent. At high concentrations barbiturates are not!

Question 24

What are some causes of status epilepticus?

Answer 24

Abrupt discontinuation of AED medication, ETOH withdrawal, cocaine abuse, poisons.

Question 25

What are the first line treatment for status epilepticus?

Answer 25

1) benzodiazepines (diazepam and lorazepam) | 2) if no response--> Fosphentoin IV (water soluble Na+ channel antagonist)

Question 26

What are two drug-drug interactions that must be accounted for in starting a patient on carbamazepine?

Answer 26

1) starting carbamazepine can INCREASE clearance of oral contraceptives. 2) starting carbamazepine can INCREASE clearance of warfarin-> increased risk of arterial/venous thrombosis.

Question 27

What is a unique feature of the newer AED's?

Answer 27

Mixed clearance, renal and liver each at 50%.

Question 28

What is the name of the drug that is an analogue of carbamazepine that has fewer side effects and what is this due to?

Answer 28

Oxcarbazepine--> less side effects due to its lack of formation of an active metabolite.

Question 29

What ion disturbance can be seen with carbamazepine and oxcarbazepine?

Answer 29

Hyponatremia due to increaed responsiveness of collecting tubules to ADH.

Question 30

What is the mode of clearance of Gabapentin and pregablin?

Answer 30

100% renal clearance. Renal ionsufficieny requires dose adjustment.

Question 31

What are the two serious boxed warning complications of Carbamazepine use?

Answer 31

1) Life threatening allergic reaction (Steven-Johnson syndrome) 2) Aplastic anemia

Question 32

What is the boxed warning complication of Lamotrigine?

Answer 32

Life threatening allergic reaction (Steven-Johnson syndrome).

Question 33

What is the potential complication of valproate and lamotrigine being administered together?

Answer 33

Together they inhibit conjugation of drugs by UGT enzymes causing accumulation of parent drug.

Question 34

What are the potential serious side effects of Levettiracetam?

Answer 34

None

Question 35

What are the potential serious side effects of Oxcarbazepine?

Answer 35

Hyponatremia

Question 36

What are the potential serious side effects of Tiagabine?

Answer 36

Stupor

Question 37

What are the potential serious side effects of Topiramate?

Answer 37

Nephrolithiasis, open angle glaucoma, hypohidrosis.

Question 38

What are the potential serious side effects of Zonisamide?

Answer 38

Rash, renal calculi, hypohidrosis.

Question 39

What 3 AEDs are class D Teratogens?

Answer 39

Valproate, carbamazepine, phenytoin

Question 40

What 4 AEDs are CYP450 inducers?

Answer 40

Carbamazepine, Phenobarbital, Phenytoin, Valproic acid.

Question 41

What are the complications associated with Carbamazepine?

Answer 41

- aplastic anemia - Leukopenia, neutropenia, thrombocytopenia, - Hypocalcemia, osteoporosis - P450 inducer

Question 42

What are the complications associated with Phenytoin?

Answer 42

- Zero-Order kinetics! - Gingival hyperplasia - Hirsuitism - hypocalcemia and osteoporosis - P450 inducer

Question 43

What is the MOA of Gabapentin?

Answer 43

- Binds to voltage-dependent Ca2+ channels. | - No significant drug interactions

Question 44

What is the MOA of Leviteracetam?

Answer 44

- Binds to synaptic vesicle protein SV2A- blunts glutamate release - Well tolerated

Question 45

What is the MOA of Pregabalin

Answer 45

- multiple MOA | - 100% renal clearance

Question 46

What is the MOA of Ezogabine?

Answer 46

- Opens voltage-gated K+ channels | - Causes urinary retention