Bipolar - Anticonvulsants

Question 1

Name the 4 Drugs in this Category

Answer 1

Valproic Acid (VPA)
Sodium Valproate (Depakote)
Carbamazepine
Lamotrigine

Question 2

VPA

vs. Sodium Valproate/Divalproex Sodium (Depakote)

Answer 2

VPA is a liquid that gives GI issues

Depakote is a powder that has half Sodium Valproate and is enterically coated to lessen GI issues

Question 3

Depakote PK:
Absorption?
Protein Binding?

Answer 3

100% absorbed

90% protein bound (high) but may be displaced by other drugs (or displace other drug bound proteins)

Question 4

VPA and Depakote Indications

Answer 4

First line for bipolar mania

Bipolar Maintenance

Question 5

Relation between drug level and response for VPA/Depakote

Answer 5

For MANIC episodes:

Response increases as drug level increases

Question 6

DDI between VPA/Depakote and Phenytoin

Answer 6

Displaces Phenytoin (anti-epileptic) and increases its levels giving possible toxicity

Question 7

DDI between VPA/Depakote and Aspirin/Caffeine

Answer 7

Aspirin and caffeine displace VPA/Depakote from serum proteins and give inc risk of toxicity

Question 8

Effect of VPA/Depakote on hepatic metabolism

Answer 8

Inhibits hepatic metabolism

Affects metabolism of phenytoin, phenobarbital, and carbamazepine

Question 9

VPA/Depakote with Lamotrigine gives?

Answer 9

Inhibited phase 2 glucoronidation of Lamotrigine (so lamotrigine levels increase)

Question 10

VPA/Depakote: Common Side Effects (6)

Answer 10

Nausea
Vomiting
Diarrhea
Tremor
Sedation
Weight Gain

Question 11

VPA/Depakote: Rare Side Effects

Answer 11

Alopecia
Dec Platelets (Thrombocytopenia) - seen more at higher doses
Inc suicide risk
Pancreatitis

Question 12

Effect of VPA/Depakote on Ammonia Level

Answer 12

Increased Ammonia level

Can give encephalopathy or delirium if severe

Question 13

VPA/Depakote Toxicity

Answer 13

Mild Inc LFT’s (reversible)

Hepatotoxicity (more with kids

Question 14

Carbamazepine Protein Binding

Answer 14

Medium

70-80%

Question 15

Carbamazepine DDI’s - does it affect CYP450? If so, how?

Answer 15

Induces CYP450 and gives inc metabolism of other drugs

Question 16

Carbamazepine and Depakote DDI

Answer 16

Depakote can bump Carba off protein binding site

Question 17

Carbamazepine DDI’s

Answer 17

Other drugs can inhibit OR induce it’s metabolism

Question 18

Carbamazepine DDI’s - Glucuronidation?

Answer 18

Induces UDP-glucuronosyltransferases

Question 19

Carpamazepine and CYP450 3A4 Inhibitors

Answer 19

CYP450 3A4 Inhibitors (fluoxetine, cimetidine, erythromycin, isoniazid) give inc levels of carba

Question 20

Carbamazepine’s effect on itself?

Answer 20

Auto-induces it’s own metabolism

Half life goes from 24 to 8 hours

Question 21

Carpamazepine and CYP450 3A4 Inductors

Answer 21

CYP450 3A4 Inductors (phenobarbital, phenytoin, primodone) give dec levels of carba

Question 22

Carbamazepine metabolism - renal or hepatic?

Answer 22

Hepatic

Question 23

Carbamazepine - Rare Side effects

Answer 23

Stevens Johnson Syndrome
Hepatotoxicity
Aplastic Anemia
Agranulocytosis
Inc Suicide Risk

Question 24

Carbamazepine - Teratogenic?

Answer 24

Yes, gives inc risk of neural tube defects (via epoxide metabolite of drug)

Question 25

Carbamazepine - Common Side effects

Answer 25

Nausea Dizziness Sedation

Question 26

Stevens Johnson Sydrome - population affected?

Answer 26

Seen more in Asian ancestry with HLA-B 1502

Question 27

Lamotrigine IS NOT used for?

Answer 27

Acute manic episode

Question 28

Lamotrigine Indications

Answer 28

Bipolar depression | Bipolar long-term maintenance

Question 29

Lamotrigine PK: | Protein Binding

Answer 29

Low protein binding (55%)

Question 30

Lamotrigine Metabolism

Answer 30

via Glucuronidation

Question 31

Lamotrigine and Sodium Valproate (Depakote)

Answer 31

Sodium Valproate (Depakote) can double Lamotrigine's plasma levels

Question 32

Lamotrigine and Oral Contraceptives

Answer 32

Oral Contraceptives can cut the Lamotrigine level in half

Question 33

Lamotrigine and Carbamazepine (or CYP3A4)

Answer 33

Gives inc metabolism of Lamotrigine and dec plasma level of Lamotrigine

Question 34

Lamotrigine - Rare Side Effects

Answer 34

``` Stevens Johnson Syndrome Blood Dyscrasias (agranulocytosis/ aplastic anemia) ```

Question 35

Lamotrigine - Common Side Effects

Answer 35

Benign Rash! | Nausea

Question 36

Majority of Stevens Johnson Syndrome occurs within how many weeks?

Answer 36

8 weeks

Question 37

What other drugs besides lithium and anticonvulsants can be used for bipolar disorder?

Answer 37

Second Generation Antipsychotics

Question 38

Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Valproic Acid/VPA

Answer 38

Acute Mania and Maintenance

Question 39

Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Carbamazepine

Answer 39

Acute Mania and Maintenance

Question 40

Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Lamotrigine

Answer 40

Maintenance and Bipolar Depression

Question 41

Which drug has the greatest potential for serious birth defects?

Answer 41

VPA (Valproic Acid) and Sodium Valproate/Depakote | Neural tube defect of 1-2% is 10-20x's the general population rate

Question 42

Carbamazepine issues during pregnancy

Answer 42

Increased risk of neural tube defect/spina bifida

Question 43

When is there an increased risk of manic episodes in relation to pregnancy?

Answer 43

During pregnancy and in the post-partum period

Question 44

Lamotrigine issues during pregnancy

Answer 44

Increased risk of cleft lip or palate