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Flashcards in Bipolar Deck (25):
1

Four valproic acid products?

- Valproic Acid (Depakene)
- Sodium Valproate (Dapakene Syrup)
- Divalproex Sodium Delayed Release (Depakote, BID)
- Divalproex Sodium Extended release (Once daily, less bioavailable)

2

Efficacy of VPA

- As effective as lithium in pure mania
- May be more effective in rapid cycling and mixed mania than lithium
- VPA is least effective in treatment of acute depression

3

Pharmacokinetics of VPA

Half-life? How many Days to reach steady state

Metabolism what pts might be influenced by this?

Proteins Binding?

- T 1/2 = 16 hrs. 3-4 days to reach Steady-steady, important for duration
- Metabolized in the liver, liver failure pts watch for hepatotoxicity
- 90% bound to albumin

4

VPA Dosing

Titration Method
- Start at ____ - 1000 mg/d in divided doses
Increase by _____ -_____ every 2-3 days up to 1000 - _______ (max?)
Why would this method not be beneficial for some patients?

Loading Dose
- 20 mg/kg in divided doses
- Typically used in?
Dosing can be given all at? When pt is stable

- Start at 500 - 1000 mg/d
- Increase by 250-500 mg/d every 2-3 days, up to 1000- 3000 mg/d
- Max 60 mg/kg

- This method is not for patients with acute agitation due to the slow efficacy

- Loading dose used in patients that are acutely agitated and severe mania patients

Dosing can be given all at bedtime if the patient is stable

5

VPA monitoring?
What guidelines do you usually follow
When is the level taken?

No therapeutic drug concentration has been established for VPA in mania

- Usually follow anticonvulsant therapeutic range (50-125 mcg/mL)
- Level is taken 12 hours after last dose.

Therapeutic Range is wide- toxic symptoms- sedation
Troph levels?

6

VPA common side effects?

Wt gain

- Common, GI switching to divalproex can help
- Sedation, tremor, wt gain
Alopecia

- Thrombocytopenia
- Hepatic Dysfunction
- Polycystic Ovarian Syndrome
- Pancreatitis
- Hyperammonemia- Acut mental status - Check

7

Monitoring with VPA

CBC- monthly for 1st 2 months
LFTs same thing
Plasma drug levels
Pregnancy test

8

VPA drug interactions?

- Inhibitor of lamotrigine metabolism, most common
- Watch with warfarin and Aspirin

9

Carbamazepine

- Structurally related to TCA
- Antimanic and prophylactic effects can be compared to Lithium and VPA
- Effective for rapid cyclers and mixed episodes

10

Carbamazepine
Metabolism

- In liver
- Induces its own metabolism
- initial t 1/2 25-65 after auto induction t 1/2 12-15

11

Carbamazepine dosing

Acute mania?

Initial 400 mg/d in divided doses w/ meals
- Increased by 200 every 2 - 4 days

- Rapid titration may cause nausea, vomiting, mild neurotoxicity (Drowsiness, dizziness, ataxia, clumsiness, diplopia)

12

Carbamazepine Therapeutic Monitoring

Target levels 5-12 mcg/ml
- higher levels may be desired in acute mania (10-14)
- Get levels 12 hours out of dose
- Drug levels should be drawn every 1-2 weeks during the 1st 2 months the every 3-6 weeks
- Levels can drop within 3 wks due to auto inductions

13

Carbamazepine SEs

- Drowsiness, Fatigue, Ataxia, Blurred vision, Diplopia

- Leukopenia, Agranularcytosis (infections not getting better)
- Steven johnson syndrome (HLA-b-1502 gene)
- Hyponatriumia
- Aplatic anemia

14

Carbamazepine Drug interactions

- Inducer
- P450
- contraceptives is the big one
- Dont want to give Carbamazepine and Clozapine together because this will increase the risk of agranularcytosis

15

Lamotrigine (Lamictal)

- FDA approved for maintenance treatment of Bipolar Disorder
- Effective in treatment of bipolar depression
- AEs- Rash, can lead to steven-johnsons
Not good at treating acute manic episode, it takes a couple weeks to take effect.

16

Lamotrigine DOsing?

1-2 25. If taking carbamazepine start a 50 then 100 and
3-4- 50. Increase by 100 at 5 wks
5- 100
6- 200
7- 200

17

Other antimanic treatments?

- Gabapentin - Negative results for bipolar disorder - has no DIs
- Oxcarbazepine
- Topiramate- Wt loss, Slows cognition
- Zonisamide- Sulfa allergy
- Levetiracetam - Lots of mood changed, cleared regally, not good for patient with psychiatric problems

18

Epidemiology fro Bipolar?

Onset is 18-44 years (mean is 20)
- Significant genetic risks

19

Mania signs and Symptoms?
FastDig

Distractibility
Insomnia
Grandiosity
Flight of ideas
Activity
Speech
Thoughtlessness

20

Severe mania signs and symptoms

- Often resembles paranoid schizophrenia
- Bizarre behavior
- Hallucinations
- Delusions
- 2/3 of pts will have psychotic symptoms

21

Course of Bipolar illness

- Average age of first manic episode is mid 20s
- Most patients will have more then one in their life
- 80% or more will have > 4 episodes
- Typically a period of normal mood in between
- Untreated episodes last several months (3-6)

22

Classifying Manic Bipolar

- Symptoms 1 wk
- grandiosity
- decreased sleep
- Pressured speech
- Racing thoughts
- Distractibility
- Increase energy
- High risk behavior
Stopped at this!

23

First trimester exposure to what causes birth defects

Li, VPA, CBZ

24

What are alternative options for pregnancy

High potency antipsychotics
Haloperidol
BDZ- Cleft palate
ECT- is an option

25

What drugs can you breast feed with?

VPA and CBZ