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Bipolar 1 vs. Bipolar 2
- Bipolar 1: full episode of mania (1 week or more) with symptoms that interfere dramatically with daily routine
- Bipolar 2: shorter episodes, some symptoms of mania, intereferes a little but not dramatically, does not lead to hospitalization
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The 4 phases of treating bipolar
- Acute: immediate; safety is main concern
- Subacute: watch carefully, suicide precautions, some antipsychotics
- Remission: discharged to day hospital or home when still symptomatic but doing better
- Maintenence: keeping them well long-term; perhaps with mood stabilizers
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Which phase of bipolar is more difficult to treat: manic or depressive phase?
Depressive
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Which mood stabilizer is probably more effective at treating the depressive phase of bipolar?
Lamotrigine
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Possible mechanisms of action of lithium
- Strong effect on second messenger systems (PIP pathway)
- Influences various transmitter systems
- Influences calcium homeostasis
- Influences processes that enhance cell protection and growth
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Lithium: mechanism of clearance
Not metabolized by liver; filtered out completely by kidney
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Half-life of lithium
15-25 hours
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Volume of distribution of lithium: high or low?
Low
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Therapeutic window of lithium: big or small? What are the consequences of this?
- Very small therapeutic window
- Consequence is that blood levels and kidney function must be regularly monitored
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As one gets older, lithium doses should be (greater/smaller) due to (increased/decreased) kidney function.
Smaller; decreased
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Lithium: Main drug interactions
- Certain diuretics (water/blood pressure meds)
- ACE inhibitors (blood pressure meds)
- NSAIDS (analgesics)
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Hydrochlorothiazide: what is it and what is its interaction with lithium?
- Diuretic
- INCREASES reabsorption of lithium by kidneys, DECREASES lithium clearance, INCREASES lithium plasma levels
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ACE inhibitors: interaction with lithium
DECREASES lithium clearance, INCREASES lithium plasma levels
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NSAIDS: interaction with lithium
REDUCES blood flow to kidneys, DECREASES clearance of lithium, INCREASES lithium plasma levels
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Side effects of lithium
- Tremor
- Renal side effects (decrease kidney function)
- Thyroid side effects (decreased thyroid function)
- Weight gain (weight loss less common)
- GI side effects (nausea, vomiting, diahrrea, etc...)
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Lithium and pregnancy: What happens to lithium levels during pregnancy and when during pregnancy? What happens to lithium levels after delivery?
- During middle trimester, kidney functioning (GFR) INCREASES.
- Thus, clearance INCREASES, and lithium levels DECREASE.
- Therefore, lithium doses should be INCREASED at this point
- After delivery, GFR decreases rapidly, so lithium dose needs to be DECREASED immediately to prevent lithium toxicity
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What is Ebstein's anomoly, when does it occur, and how does it relate to lithium use?
- Displacement of the tricuspid valve into the right ventricle of the heart (small right ventricle)
- Occurs during the first trimesterRare illness, but 10x more common with lithium use during pregnancy
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Rank in order, from best to worst to use during pregnancy (generally): mood-stabilizing anti-convulsants, antipsychotics, lithium
Antipsychotics > Lithium > Mood-stabilizing anti-convulsants
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Concept of kindling (with epilepsy) and how it relates to bipolar
- Kindling: frequent, small electrical stimulation can eventually lead to full-blown seizures; the same stimulus over time leads to a more severe effect
- Bipolar is often characterized as "behavioral kindling"
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3 mood-stabilizing anticonvulsants
- Valproate
- Carbamazepine
- Lamotrigine
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Possible mechanisms of action of valproate
- Influences process that enhance cell protection and growth (lithium has this effect as well, so perhaps this is why valproate has mood-stabilizing effects)
- Increases GABA synthesis and release
- Enhances Na+ channel activation (anti-convulsant)
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Pharmacokinetics of valproate, Depakote, and Depakote sprinkles
- Valproate absorbed rapidly
- Depakote absorbed more slowly
- Depakote sprinkles - smooth, even absorption curve, but very expensive
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Possible mechanisms of action of carbamazepine
- Enhances Na+ channel activation (anti-convulsant)
- Anti-manic effects unknown
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Carbamazepine Pharmacokinetics
- AUTO-INDUCTION: Carbamazepine induces the P450 enzyme that metabolizes it
- Auto-induction increases the clearance
- After a bit of time, half-life and steady state plasma levels DECREASE due to auto-induction
- Thus, dose must be INCREASED
- Usually one dose increase is sufficient
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Carbamazepine drug interactions
Induces activity in enzymes that destroy other drugs, so blood levels of some other drugs may decrease when on carbamazepine
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Possible mechanisms of action of lamotrigine
- Inhibits Na currents
- Inhibits glutamate release
- Mood-stabilizing effects unknown
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Antipsychotic agents generally used in _______ episodes of bipolar
Acute
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Concept of polypharmacology
Often multiple medications needed to treat bipolar
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