Bipolar - Anticonvulsants Flashcards
Name the 4 Drugs in this Category
Valproic Acid (VPA)
Sodium Valproate (Depakote)
Carbamazepine
Lamotrigine
VPA
vs. Sodium Valproate/Divalproex Sodium (Depakote)
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
Depakote PK:
Absorption?
Protein Binding?
100% absorbed
90% protein bound (high) but may be displaced by other drugs (or displace other drug bound proteins)
VPA and Depakote Indications
First line for bipolar mania
Bipolar Maintenance
Relation between drug level and response for VPA/Depakote
For MANIC episodes:
Response increases as drug level increases
DDI between VPA/Depakote and Phenytoin
Displaces Phenytoin (anti-epileptic) and increases its levels giving possible toxicity
DDI between VPA/Depakote and Aspirin/Caffeine
Aspirin and caffeine displace VPA/Depakote from serum proteins and give inc risk of toxicity
Effect of VPA/Depakote on hepatic metabolism
Inhibits hepatic metabolism
Affects metabolism of phenytoin, phenobarbital, and carbamazepine
VPA/Depakote with Lamotrigine gives?
Inhibited phase 2 glucoronidation of Lamotrigine (so lamotrigine levels increase)
VPA/Depakote: Common Side Effects (6)
Nausea Vomiting Diarrhea Tremor Sedation Weight Gain
VPA/Depakote: Rare Side Effects
Alopecia
Dec Platelets (Thrombocytopenia) - seen more at higher doses
Inc suicide risk
Pancreatitis
Effect of VPA/Depakote on Ammonia Level
Increased Ammonia level
Can give encephalopathy or delirium if severe
VPA/Depakote Toxicity
Mild Inc LFT’s (reversible)
Hepatotoxicity (more with kids
Carbamazepine Protein Binding
Medium
70-80%
Carbamazepine DDI’s - does it affect CYP450? If so, how?
Induces CYP450 and gives inc metabolism of other drugs
Carbamazepine and Depakote DDI
Depakote can bump Carba off protein binding site
Carbamazepine DDI’s
Other drugs can inhibit OR induce it’s metabolism
Carbamazepine DDI’s - Glucuronidation?
Induces UDP-glucuronosyltransferases
Carpamazepine and CYP450 3A4 Inhibitors
CYP450 3A4 Inhibitors (fluoxetine, cimetidine, erythromycin, isoniazid) give inc levels of carba
Carbamazepine’s effect on itself?
Auto-induces it’s own metabolism
Half life goes from 24 to 8 hours
Carpamazepine and CYP450 3A4 Inductors
CYP450 3A4 Inductors (phenobarbital, phenytoin, primodone) give dec levels of carba
Carbamazepine metabolism - renal or hepatic?
Hepatic
Carbamazepine - Rare Side effects
Stevens Johnson Syndrome Hepatotoxicity Aplastic Anemia Agranulocytosis Inc Suicide Risk
Carbamazepine - Teratogenic?
Yes, gives inc risk of neural tube defects (via epoxide metabolite of drug)
Carbamazepine - Common Side effects
Nausea
Dizziness
Sedation
Stevens Johnson Sydrome - population affected?
Seen more in Asian ancestry with HLA-B 1502
Lamotrigine IS NOT used for?
Acute manic episode
Lamotrigine Indications
Bipolar depression
Bipolar long-term maintenance
Lamotrigine PK:
Protein Binding
Low protein binding (55%)
Lamotrigine Metabolism
via Glucuronidation
Lamotrigine and Sodium Valproate (Depakote)
Sodium Valproate (Depakote) can double Lamotrigine’s plasma levels
Lamotrigine and Oral Contraceptives
Oral Contraceptives can cut the Lamotrigine level in half
Lamotrigine and Carbamazepine (or CYP3A4)
Gives inc metabolism of Lamotrigine and dec plasma level of Lamotrigine
Lamotrigine - Rare Side Effects
Stevens Johnson Syndrome Blood Dyscrasias (agranulocytosis/ aplastic anemia)
Lamotrigine - Common Side Effects
Benign Rash!
Nausea
Majority of Stevens Johnson Syndrome occurs within how many weeks?
8 weeks
What other drugs besides lithium and anticonvulsants can be used for bipolar disorder?
Second Generation Antipsychotics
Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Valproic Acid/VPA
Acute Mania and Maintenance
Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Carbamazepine
Acute Mania and Maintenance
Of Acute Mania, Maintenance, Bipolar Depression - which ones are treated by Lamotrigine
Maintenance and Bipolar Depression
Which drug has the greatest potential for serious birth defects?
VPA (Valproic Acid) and Sodium Valproate/Depakote
Neural tube defect of 1-2% is 10-20x’s the general population rate
Carbamazepine issues during pregnancy
Increased risk of neural tube defect/spina bifida
When is there an increased risk of manic episodes in relation to pregnancy?
During pregnancy and in the post-partum period
Lamotrigine issues during pregnancy
Increased risk of cleft lip or palate
