Bipolar Disorder

Question 1

Lithium

Answer 1

Mechanism:
Unknown, but may stabilize neurons:
- Normalizes increased intracellular Na+ & Ca2+
- Decreases presynaptic DA activity & alters 5-HT activity
- Interferes w/ receptor-activated phosphatidyl inositol turnover in DAG/IP3 2nd messenger pathway

Use: Bipolar disorder

Toxicity:

• N&V, diarrhea, tremor, ataxia – don’t give anti-emetic (will mask sx)
• CNS - tremors, confusion, motor abnormalities, seizures
• Thyroid – decreased fxn due to uncoupling of TSH GPCRs
• Renal – Li-induced nephrogenic diabetes insipidus due to ADH GPCR uncoupling
• Cardiac – depresses SA node & T-wave amplitude

Metabolism:

• Almost totally eliminated in urine within 24 hrs
• Reabsorption occurs w/ Na+ in proximal tubule, so Na load/depletion will affect Li+ clearance
• Therapeutic index ~ 2, so monitor blood lvls closely
• Pregnancy category D

Interaction:
Toxicity risk with drugs that alter Na reabsorption and/or GFR:
- Na-depleting diuretics
- ACE-Is & NSAIDs decrease GFR & increase Li+ reabsorption

CI: history of seizures, sick-sinus cardiac rhythm

Question 2

Valproate

Answer 2

increase GABA levels
Use: can be used in bipolar disorder when patients cannot tolerate lithium
(may inhibit HDAC –> increase acetylation –> inc. BDNF –> + synaptic plasticity and cell integrity)

Question 3

Carbamazepine

Answer 3

blocks sodium channels;
inhibits uptake and release of NE

Use: can be used in bipolar disorder when patients cannot tolerate lithium
(may inhibit HDAC –> increase acetylation –> inc. BDNF –> + synaptic plasticity and cell integrity)

Question 4

Lamotrigine

Answer 4

blocks sodium channels
Use: can be used in bipolar disorder when patients cannot tolerate lithium
(may inhibit HDAC –> increase acetylation –> inc. BDNF –> + synaptic plasticity and cell integrity)