Pharm: Seizures

Question 1

Diazepam

Answer 1

“Valium”
= Benzodiazepine (clonazepam, lorazepam)
** Given IV for status epilepticus!!!

MOA: enhance GABA-mediated Cl- influx and enhance the generation of inhibitory membrane potentials

PK: extremely lipophilic

USE: Status epilepticus, myoclonic, partial, generalized tonic-clonic seizures

ADR: can cause sedation/drowsiness and decreased respiratory drive

Question 2

Carbamazepine

Answer 2

“Tegretol”
MOA: prolongs inactivated state of Na+ channel

PK: potent CYP inducer
** Autoinduction **

USE: Partial seizures, generalized tonic-clonic, trigeminal neuralgia, mania in bipolar disorder

Unique ADRs: hyponatremia, blood dyscrasias (agranulocytosis), *** leukopenia, SJS

Question 3

Ethosuximide

Answer 3

“Zarontin”

• MOA: reduces low threshold Ca2+ (T-type) current

PK: long t1/2 40 hours

USE: ** ONLY Absence seizures

Unique ADRs: gastric distress

Question 4

Gabapentin

Answer 4

“neurontin”

MOA: bind α2δ subunit of voltage-gated N-type Ca2+ channels, decrease Ca2+ entry, decrease synaptic release of glutamate

PK: not metabolized

USE: Partial seizures, generalized tonic-clonic, neuropathic pain, post-herpetic neuralgia

Unique ADRs: headache, tremor

Question 5

Lamotrigine

Answer 5

“Lamictal”

MOA: prolongs inactivated state of Na+ channel

USE: Partial seizures, generalized tonic-clonic, bipolar disorder

Unique ADRs: skin rash

Question 6

Levetiracetam

Answer 6

“Keppra”

MOA: binds synaptic vesicular protein SV2A. Modifies synaptic release of glutamate and GABA.

USE: Partial seizures, generalized tonic-clonic, myoclonic seizures

Unique ADRs: serious mood and behavioral changes (less common)

Question 7

Phenytoin

Answer 7

= “Dilantin”

MOA: prolongs inactivated state of Na+ channel

• highly protein bound!!
• CYP2C9/19 metabolism

USE: (this is the go to, works for everything but absence) Partial seizures, generalized tonic-clonic

Unique ADRs: gingival hyperplasia, hirsutism

• Cardiac effects: hypotension, bradycardia, arrhythmia
• can cause SJS

Question 8

Valproic Acid

Answer 8

• Divalproex
  = “Depakote”

MOA: prolongs inactivated state of Na+ channel, may block NMDA receptor mediated excitation, may increase levels of GABA

PK: highly protein bound

USE: (ALL ! )Absence seizures, myoclonic seizures, generalized tonic-clonic, partial seizures, status epilepticus, bipolar disorder, migraine prophylaxis

Unique ADRs: GI distress, fine tremor, weight gain and hair loss!

Question 9

simple partial seizure

Answer 9

= minimal, normal consciousness, presered awareness

Question 10

complex partial seizure

Answer 10

• localized onset but discharge becomes widespread; almost always involving limbic system
• Patient may have automatisms (lip smacking, swallowing, fumbling, scratching), memory loss, or aberrant behavior.

Question 11

secondarily generalized seizure

Answer 11

• Partial seizure immediately precedes a generalized tonic-clonic seizure.

Question 12

tonic-clonic

Answer 12

= grand-mal seizure

(1) Sudden, sharp tonic contraction followed by rigidity and clonic movements.
(2) Patient may cry/moan, lose sphincter control, bite tongue, or develop cyanosis.
(3) After seizure, patient may have altered consciousness, drowsiness, or confusion (postictal).

Question 13

absence seizure

Answer 13

= petit mal

(1) Sudden onset and abrupt cessation; altered consciousness; a blank stare.
(2) Occurs in young children through adolescence.

Question 14

myoclonic seizure

Answer 14

Brief, shock-like muscle contractions; occur in wide variety of seizures

Question 15

atonic seizure

Answer 15

(1) Sudden loss of postural tone: head drop, fall to floor, slumping.
(2) Many patients wear helmets to prevent head injury.

Question 16

three MOAs of AED’s (anti-eleptic drugs)

Answer 16

Limit sustained, repetitive firing of neurons, mediated by promoting the inactivated state of voltage-gated Na+ channels

Enhanced γ-aminobutyric acid (GABA) mediated synaptic inhibition, mediated by presynaptic or postsynaptic actions

Inhibition of voltage-gated Ca2+ channels

Question 17

which are highly protein bound?

Answer 17

phenytoin, valproic acid

Question 18

common ADR’s amongst all?

Answer 18

Sedation
Dizziness
Blurred or double vision
Difficulty concentrating
Ataxia

Question 19

what to watch out for w/ warfarin?

Answer 19

• phenytoin

- carbamazepine

Question 20

autoinduction?

Answer 20

carbamazepine

Question 21

tx for partial seizures?

Answer 21

Carbamazepine
lamotrigine
oxcarbazepine
levetiracetam

Question 22

topiramate

Answer 22

“topamax”

MOA: actions on Na+ channels, GABAA receptors, high-voltage Ca2+ currents, may act on glutamate/NMDA receptors

Partial, generalized tonic-clonic, Lennox-Gastaut, infantile spasms, absence seizures, migraine

Unique ADRs: paresthesias, nervousness, weight loss

Question 23

tx of primary generalized tonic clonic seizure

Answer 23

Valproate –or– lamotrigine –or– levetiracetam

Question 24

Absence seizure tx?

Answer 24

Ethosuximide –or– valproate

Question 25

Atypical absence, myoclonic or atonic tx?

Answer 25

Valproate –or– lamotrigine –or– levetiracetam

Question 26

DDI’s of phenytoin?

Answer 26

Protein binding (sulfonamides)

Competes for metabolism CYP2C9 (warfarin) & 2C19

Also results in enzyme induction (oral contraceptives)

Question 27

DDI’s of carbamazepine?

Answer 27

Enzyme induction (phenytoin, oral contraceptives)

Question 28

DDI’s of Valproic Acid?

Answer 28

Enzyme inhibition (carbamazepine)

Question 29

DDI of Lamotrigine?

Answer 29

Oral contraceptives may decrease lamotrigine concentrations

Question 30

AED’s and pregnancy?

Answer 30

1. Interactions with oral contraceptives
   Effectiveness of OCs reduced by (likely due to induction of CYP3A4):
   - carbamazepine, oxcarbamazepine, phenobarbital, phenytoin, primidone, rufinamide
2. Potential teratogenic effects:
   - Increased risk of congenital malformations: phenytoin, valproate, topiramate

Question 31

look at questions!

Answer 31

at end of slide