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Lithium Drug-Drug interactions (increases Li levels)
- ACE (200-300%)
- ARB(200-300%)
- thiazide diuretics (50%)
- NSAIDs (20-30%)
- COX2 inhibitor (20-30%)
- salt restricted diet
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Drugs that interact w/ Lithium causing neurotoxicity (an adverse effect)
- carbamazepine
- diltiazem
- losartan
- methyldopa
- metronidazole
- penytoin
- verapamil
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Enhance renal elimination of Lithium
- caffine
- theophylline
- AVOID: do not use lithium is there are kidney issues
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Lamotrigine adverse effects
- rash
- steven johns syndrome (SJS)
- aseptic meningitis (resolved by discontinuation of med)
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Lithium theraputic conc for steady state
- maintenance: 0.6 - 1.2
- acute manic: 0.8 - 1.5
- Lithium toxicity: 1.5 mEq/L
- Severe Lithium toxicity: 2.0 mEq/L
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Classifications of Bipolar Disease
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5 types of mood disorders
- Mania
- Hypomania
- Major Depressive
- Mixed State (Depressive & Manic - most volatile)
- Rapid Cycling (4 or more episodes in a year)
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Hypomania
- duration is usually shorter than mania
- "artistic" state of disorder
- flight of ideas
- clever thinking
- increase in energy
- If hospitalized: then automatically classify as manic and bipolar I
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Glycogen Synthase-kinase (GSK3)
- involved in the regulation of circadian rhythm through phosphorylate of transcription factors
- GSK3 regulates: PER, TIM, CLK transcription factors by changing phosphorylation states
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Lithium adverse effects
- Initial side effects: GI distress (nausea, vomiting, dyspepsia, and diarrhea)
- polydipsia (thirst)
- polyuria (excessive piss)
- nocturia (peeing at night)
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Lithium Toxicity
- occur at blood lebels greater than 1.5
- Severe toxicity: at levels greater than 2.0
- Treat severe intoxiciation: Hold next dose of lithium, IV NS, manage electrolytes
- If blood levels over 6.0: begin hemodialysis
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Carbamazepine & Oxcarbazepine
- both efficacious for acute mania
- side effects: nausea, sedation, rash, dizziness
- Carbamazepine side effect: induces hepatic metabolism
- Oxcarbamazepine side effects: hyponatremia
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Valporic Acid
- mood stabilizer
- superior to lithium pts w/ rapid cycling, mixed or dysphoric mania
- loading dose: 20-30mg/kg or add a 0 to pts weight (lb)
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Lamotrigine
- effective for bipolar depression and maintenance
- NOT mania
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Atypical antipsychotics
- Olanzapine, aripiprazole, ziprasidone: aprroved for maintenance
- Acute treatment of mania: olanzapine, risperidone, quetiapine, siprasidone, aripiprazole, asenapine
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Manic/mixed episode treatments
- atypical antipsychotic plus mood stabilizer
- mood stabilizers: Lithium, VPA
- Monotherapy: if not severe episode Li, VPA, or atypical can be used as monotherapy
- In lieu of VPA or Li: can use Carbamazepine, Oxcarbazepine
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Depressie Episode treatements
- lamotrigine
- lithium
- olanzapine-fluoxetine combo
- Li has positive evidence against suicidal behavior (like clozapine)
- Mood stabilizer not on board: do not use antidepressant w/o mood stabilizer b/c it can trigger manic episode
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Maintenance Treatment
- Lamotrigine: more effective against depressive
- Lithium: more effective against manic (suicide)
- atypical: olanzapine, aripiprazole, ziprasidone
- least risk for metabolic side effects: aripiprazole, ziprasidone
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Initial Lithium Dosing
- based on weight
- 100lb: 300mg BID
- 150lb: 300mg TID or 450mg BID
- 200lb: 600mg BID
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calculate steady state of Lithium
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Lithium's tremor treatment
- propranolol
- divide the dosing
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Valporic Acid adverse effects
- upset stomach: treat by eating w/food or enteric coating
- tremor: treat by dividing doses or propranolol
- daytime sleepiness: take medication before bedtime
- weight gain: counsel on diet & exercise
- alopecia: vitamin E or seleium
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Dosing Schedule for Lamotrigine
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Pregnancy
- Treat w/: haloperidol, respirodone
- Lithium: category D (Ebstein's anomaly)
- Valporic Acid: category D (spina bifida, low IQ, facial changes)
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Carbamazepine
- target levels: 4-12 mcg/ml
- initial dose: 200-600mg
- acute mania: increase by 200mg/day up to 800-1000mg/day
- minor side effects: fatigue, diplopia, blurred vision, ataxia
- Major side effects: hepatic failure, agranulocytosis, aplastic anemia, thrombocytopenia
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