15) Anti-Seizure

Question 1

Epilepsy

Answer 1

• Group of chronic syndromes that involve the recurrence of seizures (ie, limited periods of abnormal discharge of cerebral neurons)

Question 2

Seizure

Answer 2

• Occurs when a burst of electrical impulses in thebrain escape their normal limits
• Spread to neighboring areas and create an uncontrolled storm of electrical activity
• Electrical impulses can be transmitted to the muscles, causingtwitches or convulsions

Question 3

Sodium channel blockade MOA

Answer 3

• Block voltage-gated sodium channels in neuronal membranes
• Rate-dependent (block increases with increased frequency of neuronal discharge)
• Prolonged inactivated state of the Na+channel and the refractory period of the neuron

Question 4

Benzodiazepenes

Answer 4

• Interact with specific receptors on the GABAAreceptor–chloride ion channel
• Facilitate the inhibitory effects of GABA

Question 5

Phenobarbitaland other barbiturates

Answer 5

• Enhance the inhibitory actions of GABA but interact with a different receptor site on chloride ion channels
• Results in an increaseddurationof chloride ion channel opening

Question 6

GABA aminotransaminase (GABA-T)

Answer 6

• Important enzyme in the termination of action of GABA
• Irreversibly inactivated by vigabatrin
• Inhibits a GABA transporter (GAT-1) in neurons and glia, prolonging the action of the neurotransmitter

Question 7

Ethosuximide

Answer 7

• Inhibits low-threshold (T type) Ca2+currents, especially in thalamic neurons
• Similar action is reported forvalproic acid,as well as for bothgabapentinandpregabalin with unknown mechanism

Question 8

Levetiracetam

Answer 8

• Binds the SV2A protein on glutamate-containing transmitter vesicles
• Reduces glutamate release

Question 9

Retigabine

Answer 9

• Enhances K+channel activity

- Inhibits depolarization of glutamate terminals

Question 10

Perampanel

Answer 10

• Noncompetitive antagonist at glutamate AMPA receptors

- Prevents spread of abnormal excitation in susceptible neurons

Question 11

Felbamate

Answer 11

• Blocks glutamate NMDA receptors

Question 12

Althoughphenobarbitalacts on both sodium channels and GABA-chloride channels,

Answer 12

• It also acts as an antagonist at some glutamate receptors

Question 13

Topiramate

Answer 13

• Blocks sodium channels
• Potentiates the actions of GABA
• May also block glutamate receptors

Question 14

The oral bioavailability of phenytoin

Answer 14

• Variable because of individual differences in first-pass metabolism

Question 15

Phenytoin metabolism

Answer 15

• Nonlinear elimination kinetics

Question 16

Phenytoin binding

Answer 16

• Binds extensively to plasma proteins (97–98%)
• Free (unbound) phenytoin levels in plasma are increased transiently by drugs that compete for the same binding (eg, carbamazepine, sulfonamides, valproic acid).

Question 17

The metabolism of phenytoin is enhanced in

Answer 17

• Presence of inducers of liver metabolism (eg, phenobarbital, rifampin) and inhibited by other drugs (eg, cimetidine, isoniazid)

Question 18

Phenytoin itself induces

Answer 18

• Hepatic drug metabolism

- Decreases the effects of other antiepileptic drugs including carbamazepine, clonazepam, and lamotrigine.

Question 19

Fosphenytoin

Answer 19

• Water-soluble prodrug form of phenytoin

- Used parenterally

Question 20

Carbamazepine

Answer 20

• Induces metabolism of many other anticonvulsant drugs (including clonazepam, lamotrigine, and valproic acid)
• Metabolism can be inhibited by other drugs (eg, propoxyphene, valproic acid)

Question 21

Valproic acid inhibits

Answer 21

• Metabolism of carbamazepine, ethosuximide, phenytoin, phenobarbital, and lamotrigine

Question 22

Valporic acid competes for

Answer 22

• Phenytoin plasma protein binding sites

Question 23

Hepatic biotransformation of valproic acid leads to formation of

Answer 23

• A toxic metabolite that has been implicated in the hepatotoxicity of the drug

Question 24

Drugs eliminated by the kidney, largely in unchanged form

Answer 24

• Gabapentin
• Pregabalin
• Levetiracetam
• Vigabatrin

Question 25

Neural tube defects (eg, spina bifida) are associated with the use of

Answer 25

- Valproic acid - Carbamazepine - Phenytoin

Question 26

Most of the commonly used anticonvulsants are

Answer 26

- CNS depressants - Respiratory depression may occur with overdosage - Life-threatening toxicity

Question 27

Fatal hepatotoxicity has occurred with

Answer 27

- Valproic acid

Question 28

Lamotrigine has caused

Answer 28

- Skin rashes - Life-threatening Stevens-Johnson syndrome - Toxic epidermal necrolysis

Question 29

Zonisamide may also cause

Answer 29

- Severe skin reactions - Reports of aplastic anemia and acute hepatic failure have limited the use of felbamate to severe, refractory seizure states

Question 30

Withdrawal from antiseizure drugs should be accomplished gradually to avoid

Answer 30

- Increased seizure frequency and severity

Question 31

Cytochrome P450 enzyme system inducers

Answer 31

- Phenobarbital - Primidone - Phenytoin - Carbamazepine - Felbamate (CYP3A) - Topiramate (CYP3A) - Oxcarbazepine (CYP3A)

Question 32

Cytochrome P450 enzyme system inhibitors

Answer 32

- Valproate - Topiramate (CYP2C19) - Oxcarbazepine (CYP2C19) - Felbamate (CYP2C19)

Question 33

Anti-seizure drugs with active metabolites

Answer 33

- Carbamazepine - Primidone - Fosphenytoin

Question 34

Anti-seizure drugs with zero order kinetics

Answer 34

- Phenytoin

Question 35

Anti-seizure drug that can cause gingival hyperplasia

Answer 35

- Phenytoin induced gingival hyperplasia

Question 36

Fosphenytoin is a prodrug that will become

Answer 36

- Phenytoin

Question 37

General adverse effects of anti-seizure medications

Answer 37

- Nausea/vomiting - Drowsiness/sedation - Ataxia - Rash - Hyponatremia - Weight gain/loss - Teratogenicity - Osteoporosis