Drug Therapy of Seizure Disorders

Question 1

Injectable drugs

Answer 1

Phenytoin, phosphrnytoin, valproic acid, levetiracetam

Question 2

1st vs. 2nd and 3rd gen

Answer 2

1st are mainstays but oftne have more SEs

Question 3

Na blocker rationale

Answer 3

Act at presynaptic to suppress pre-synaptic generation of APs

Question 4

Na blocker selectivity

Answer 4

Frequency dependent block

Bind in the open or inactivated state…if more often open or inactivated then more binding…drug accumulates and has greater effect

Question 5

Pheny and fosphy MOA and uses

Answer 5

Ph - GTC, Status, focal

Fos - only Status

Phenytoin better for LT, fos better for status

Question 6

Fos vs. pheny toin and how it is metabolized and drug interactions

Answer 6

Phenytoin is not as water soluble…fos is a prodrug

Hepatic metabolism

Induces CYP2C9 and enhances metabolism of other drugs

Question 7

Phenytoin dosing

Answer 7

As a certain point, non-linear pharmacokinetics

Question 8

SE of phenytoin

Answer 8

Hypotension/cardiac inhibition (limit rate of IV)
Decreased bone mineral density
Gingival overgrowht

Some CNS

Question 9

SE of phnytoin more serious

Answer 9

SJS
DRESS - hepatic necrosis is danger

If it leaks out, could cause Purple Glove syndrome

Question 10

Carbamzaepine MOA and uses

Answer 10

GTC, focal

Na channel blocker

Used for long term

Can aggrevate absence seizures

Question 11

Carbamazepine metab and pharmacokinetics vs. phenytoin

Answer 11

Induces multiple CYP450 isozymes

First order elimination makes dosing safer…still tons of interactions

Question 12

Carbamazepine dosing

Answer 12

It autoinduces the enzymes that metabolize it so need to start low and titrate high

Question 13

Carbamazepine and serious side effects

Answer 13

SJS - Esp east asian (HLA-B*1502 genotype)

Question 14

Carb other SEs

Answer 14

Ataxia and other CNS
Decreased bone mineral density

Other hypersensitivty

Question 15

Lamotrigine MOA and what it works on

Answer 15

GTC and focal

Works on absence but not prefferred

Na blocker and weak Ca blocker

Question 16

Lamotrigine elimintion and drug interactions

Answer 16

Hepatic glucuronidation

It has miniamal effects on other drugs

Carbamazepine decrease blood levels by inducing elimination

Valproic acid increases blood levels by inhibitng elimiantion

Question 17

Lamotrigine SEs

Answer 17

CNS

Hypersensitivity (SJS)…avoid in pediatrics…dose titrate

Question 18

Vaproic acid MOA and uses

Answer 18

Mostly absence and focal

Also GTC and status

Na channel blocker and Ca blocker

Best for complicated syndromes with multiple seizrue types

Question 19

Mech of valproic acid

Answer 19

Mostly on Na channels
Low-threshold Ca blocker
Enhancment of GABA

Question 20

Valproi acid elimination and drug interactions

Answer 20

Glucuronidation (also fatty acid)

Phenytoin and carbamazepine induce enzymes that metabolize so will decrease concentration

Question 21

Valrpoic acid SEs

Answer 21

Teratogenic
Hepatotoxicity/pancreatitis (younger)
CNS

Question 22

Topiramate MOA and uses

Answer 22

GTC and focal

Na nlocker
Glutmate antaginist
GABA nergic enhancer

Question 23

Topiramate SEs

Answer 23

Sedation, cog
Metabolic acidosis
Weight loss

Question 24

Topiramate elimination and drug interactions

Answer 24

Primarily renal elimination

Few drug interactions except with carbonic anhydrase inhibitors

Question 25

Ethosuximide MOA and use

Answer 25

Generalized absence Blcoker of neuronal low-threshold Ca channels

Question 26

Mech of low threshold Ca channels

Answer 26

Ca channels open and depoalizre thalamic relay neurons The PDS brings relay neuron closer to threshold for Na Burst of APs APs conducted to cortical neurons Ethosuximide disrupts these Ca channels

Question 27

Ethosuximde drug interactions and SE

Answer 27

Mostly CYP3A4 but some renal GI distress and bone marrow depression Preferred for absence seizures because greater efficacy than lamotrigine and less effect on cog than valprpoci

Question 28

Levetiracetam MOA and use

Answer 28

GTC, status, Focal Useful for combo Synaptic transmission modulator Binds to SV2A, secretory vesicle glycoprotein

Question 29

Levetiracetam eliminatioin and SEs

Answer 29

Renal excretion | Fatigue, asthenia, behavioral

Question 30

Mechs of ``` Pheny Carba Lamo Topir Valpro Etho Levetir ```

Answer 30

``` Na channel Na channel Na, Ca channel Na, gabanergic, glutamate antag Na, Ca, enahnce Gaba Ca Decrease vesicle release by binding to SV2A ```

Question 31

Protoypes that alter hepatic metabolism

Answer 31

Phenytoin - induces glucordination of lamotrigine and valproic acid Carb - induces glucuronidation of lamotrigine and valproic acid Valproic acid - inhibits glucuronidation of lamotrigine