Antiepileptics

Question 1

All Old Generation Antiepileptics (List)

Answer 1

Phenytoin (Dilantin)
Fosphenytoin (Cerebyx)
Carbamazepine (Tegretol)
Ethosuxamide (Zarontin)
Valproic Acid derivatives: Sodium Valproate (Depakene) and Valproic Acid (Depakote)
Phenobarbital (Luminal)
Primidone (Mysoline)

Question 2

GABA

Answer 2

The major inhibitory neurotransmitter

Question 3

Indication for Phenytoin(Dilantin)

Answer 3

Primary generalized and partial seizures. NOT absence seizures.

Question 4

Mechanism of Phenytoin(Dilantin)

Answer 4

Blocks Na+ channels associated with depolarization, depolarization and membrane stability.

Also prolongs inactive period of Na+channels to stop the rapid firing of action potentials.

Question 5

Cardiac effects of Phenytoin (Dilantin) . dose dependent.

Answer 5

Widening of QRS.

Remember, do NOT give Dilantin for TCA overdose as they widen QRS as well.

Question 6

Phenytoin (Dilantin) routes of administration

Answer 6

Dilantin infatabs- chewable (50mg)
Dilantin suspensions- 30mg/5ml or 125mg/5ml
capsules- 30 mg or 100mg
Injection- 50mg/ml, contains propylene glycol
No IM Injection

Question 7

Max rate of Phenytoin (Dilantin) IV Infusion

Answer 7

50mg/minute

Question 8

Prodrug of Phenytoin (Dilantin)

Answer 8

Fosphenytoin ( Cerebyx)

Max infusion 150mg/minute

Question 9

Benefit of Fosphenytoin (Cerebyx)

Answer 9

no propylene glycol (tachydysrhythmias and hypotension)

can be given IM

Question 10

Phenytoin (Dilantin) reference range

Answer 10

7-20mg/L
some say 10-20mg/L= measures both bound and the free fraction (1-2mg/L)
free fraction is the “active” form of the drug

Question 11

Average dose of Phenytoin (Dilantin) adult and peds

Answer 11

Adult maint (oral)=300-400mg/day PO
Pedi maint = 4-8mg/kg/day (1-2 divided doses)

Question 12

Phenytoin (Dilantin) toxicity doses and symptoms

Answer 12

> 20mg/L=nystagmus
30mg/L=ataxia, seizures
40mg/L=lethargy, altered consciousness, coma. must protect airway.

Question 13

Phenytoin (Dilantin) Side effects

Answer 13

Sedation, gingival hyperplasia, hirsutism, hyperglycemia, osteoporosis, teratogenicity (cat D), DRESS, megaloblastic anemia (due to folate def.)

Question 14

Phenytoin (Dilantin) is an inducer of:

Answer 14

CYP3A4

Question 15

Indications for Carbamazepine (Tegretol)

Answer 15

1)partial and secondarily generalized tonic-clonic seizures
2) DOC for trigeminal neuralgia
3) mood stabilizer in bipolar disorder
NOT myoclonic seizures (worsens)

Question 16

Carbamazepine (Tegretol) Mech of Action

Answer 16

Blocks Na+ channels (similar to phenytoin)

has similar shape and is related to other antidepressants

Question 17

Carbamazepine (Tegretol) therapeutic range

Answer 17

4-12 mg/L

Question 18

active metabolite of Tegretol

Answer 18

10,11 epoxide.

causes induction and its own metabolism by inducing CYP3A4

Question 19

DDI of Tegretol

Answer 19

Inducer of CYP1A2, 2B6, 2C8, 2C9, 2C19, 3A4

decreases Warfarin’s effect
causes oral contraceptive failure
erythromycin inhibits metabolism

Question 20

pharmacogenetics concern with Tegretol

Answer 20

HLA-B*1502 allele: causes a severe rash (SJS, TEN) win Han Chinese, asian populations, or people from Thailand, India, Singapore, or Malaysia
Life threatening skin reaction

Question 21

Side Effects of Carbamazepine (Tegretol)

Answer 21

HLA-B*1502 allele skin reaction
Leukopenia - caution with BMS its
Aplastic Anemia and agranulocytosis - Black box
Hyponatremia -stimulates release of ADH
Drowsiness
fatigue

Question 22

Indications for Oxcarbamazepine (Trileptal)

Answer 22

initial or adjunct therapy for partial seizures

not ‘approved’ for bipolar but is often used as a mood stabilizer when CBZ has adverse SE

Question 23

available routes/formulations of Trileptal

Answer 23

Tablet= 150, 300 or 600 mg as either IR or XR
Suspension=300mg/5ml (contains ethanol) - don’t give with Antabuse or flagyl*

IR give without regard to food
XR should be taken on empty stomach

Question 24

Trileptal pharmacokinetics and DDI

Answer 24

Strong inducer of CYP3A4 and UDP
inhibits CYP2C19

lowers Oral contraceptives
increases levels of phenobarbital and phenytoin

Question 25

Oxcarbamazepine (Trileptal) Side Effects

Answer 25

HA, dizziness, nystagmus, blurred vision, n/v, rash, hyponatremia less than CBZ (some cross-sensitivity)

Question 26

Eslicarbazepine (Aptiom) indications

Answer 26

usually adjunct therapy | partial onset seizures

Question 27

Eslicarbazepine (aptiom) dosing

Answer 27

400 mg tablet PO max 1200mg/day

Question 28

eslicarbazepine (aptiom) metabolism

Answer 28

rapid metabolism by first pass effect into eslicarbazepine and oxcarbazepine

Question 29

Valproic acid derivatives indications

Answer 29

``` Complex partial seizures (mono or adjunct) status epilepticus absence seizures bipolar disorder migraine prophylaxis ```

Question 30

Valproic acid formulations

Answer 30

``` Valproic acid (Depakene, Stavzor) caps/syrup Depakote (enteric coated tabs)-often preferred ```

Question 31

Valproic acid mechanism of action

Answer 31

partial Na+channel blocker | increases GABA levels by inhibiting GABA degradation

Question 32

Valproic acid reference range

Answer 32

50-125 mg/mL toxicity starts at 150-200

Question 33

Valproic acid SE

Answer 33

GI (common): n/v/d dyspepsia weight gain, hepatotoxicity, pancreatitis, tremors, dose dependent thrombocytopenia, teratogenicity due to folate deficiencies *hyperammonemia (NH3+) - consider L-carnitine therapy if asymptommatic=100mg/kg/day in 4 doses PO if symptomatic = 100mg/kg IV (max 6g) over 30 min then paint of 15mg/kg q4 hours over 10-30 min

Question 34

Valproic acid DDI

Answer 34

``` Lamotrigine (lamictal) Phenytoin (dilantin) Phenobarbital (Luminal) CBZ ethosuximide (zarontin) AZT (zidarvidine) ```

Question 35

ethosuximide (Zarontin) indications

Answer 35

ONLY pure absence seizures | not used with atypical absence seizures

Question 36

ethosuximide (Zarontin) reference range

Answer 36

60-100mcg/mL

Question 37

ethosuximide (Zarontin) SE

Answer 37

``` GI Gastritis (primary) fatigue, HA, neuropsychotic behavior Rash (SJS) Leukopenia (check CBC) lupus-like syndrome ```

Question 38

phenobarbital (Luminal) indications

Answer 38

as an alternative for partial or generalized tonic-clonic seizures *worsens absence seizures usually 2nd line. may be seen in pregnancy

Question 39

phenobarbital (Luminal) MOA

Answer 39

enhances GABA mediated inhibition by increasing Cl Channel openings: hyperpolarizes the neuron

Question 40

Phenobarbital (Luminal) dosing

Answer 40

Peds 2-8mg/kg/day in 1-2 doses | adults 90-180 mg once or 2 doses

Question 41

Phenobarbital (Luminal) reference range

Answer 41

desired 15-40mg/L Toxic: >50mg/L= resp depression

Question 42

Clinical issues with Phenobarbital (Luminal)

Answer 42

inducer of CYP450 and UGT enzymes: DI Sedation as main SE can develop tolerance to phenobarb

Question 43

Primidone (Mysoline) indications

Answer 43

Same as phenobarbital alternative for partial and generalized tonic clonic seizures

Question 44

Primidone (mysoline) metabolism

Answer 44

metabolized to PEMA (Phenylethylmalonamide) and Phenobarbital

Question 45

Primidone (Mysoline) dosing

Answer 45

adults: 750-1000 mg/day in 3-4 div doses (Max 2 g) Peds: 10-25 mg/kg/d in 2-3 div doses also give folic acid supplement

Question 46

Primidone (Mysoline) SE

Answer 46

``` CNS depression Sedation Confusion Suicidal ideation *megaloblastic anemia: due to lowering of RBC and CSF folate levels ``` avoid in pregnancy