12 - Lithium Flashcards
Health Canada approved uses of lithium
- Acute manic episodes
- Maintenance tx of bipolar disorder
What is the main criteria for bipolar disorder?
Must have an effect on life and not be caused by any other drugs or medical conditions
Goals of therapy w/ lithium
- Acute stabilization = bring pt w/ mania or depression to symptomatic recovery w/ stable mood
- Maintenance = relapse prevention, reduction of sub-threshold sx, social and occupational functioning
Initial dosing of lithium for bipolar disorder
900-2100 mg/day (15-20 mg/kg/day)
Maintenance dosing of lithium for bipolar disorder
600-1800 mg/day
Compare and contract single daily dose vs. multiple daily dose of lithium
- Single dose = increased compliance, decreased polyuria, usual dosing time at bedtime, total dose 1800 mg or less
- Multiple dose = increased stability, decreased peak and trough related adverse effects, usual dosing BID or TID, need 12 h period between last dose and first dose (ex: last dose 9 pm and next morning dose no earlier than 9 am)
Is single or multiple daily dosing preferred when starting pt on lithium?
- Multiple daily
- Once stabilized, can consider single dose but this will alter the 12 h lithium concentration, so monitor and make dosing adjustments if needed
How is lithium excreted?
Primarily renal
What factors affect the clearance of lithium?
- Circadian rhythm (day > night)
- Affective phase (manic > non-manic)
- Age (young > old)
- Pregnant > non-pregnant
What is important to note about the distribution of lithium and when to take levels?
- Two compartment model, so has long distribution phase before elimination phase
- Take levels 12 h after last dose
What are some factors that affect serum lithium concentrations and what is the end result?
- Decreased water balance (ex: strenuous exercise, excessive sweating, diarrhea, or vomiting) increases serum [Li]
- Decreased sodium balance (ex: low salt diet, thiazides, ACEis) increases serum [Li]
- Decreased renal function (ex: age, drugs) increases serum [Li]
What are some factors that can lower lithium levels?
- Pregnancy
- Obesity
- Acetazolamide, methylxanthines
What are some factors that can raise lithium levels?
- Dehydration
- Renal impairment
- Cirrhosis
- ACE inhibitors, NSAIDs, thiazides
Formula for lithium clearance
Cl Li (mL/min) = 0.2 * CrCl
Formula for lithium clearance (non-manic)
Cl Li (L/day) = 0.288 * CrCl
Formula for lithium clearance (manic)
Cl Li (L/day) = 0.432 * CrCl
Formula to find Css of lithium
Css = [F * (dose/tau)] / Cl Li
OR
dose/tau = (Css * Cl Li) / F
How do you convert dose of lithium in mg to mmol
300 mg LiCO3 = 8.12 mmol
Target Li+ levels in acute mania
- 0.8 - 1.2 mmol/L
- Pick 0.8 as target when calculating dose; its okay to round down dose and go slightly below range
- 1 - 1.2 mmol/L in nonresponders
Target Li+ levels for maintenance
- 0.6-0.8 mmol/L (as low as 0.4 in elderly)
- 0.9 - 1 mmol/L in nonresponders
How long does it take lithium to reach steady state? What does this mean when taking levels?
- Steady state in 4-5 days
- Take levels 12 h +/- 30 mins after last evening dose at least 4-5 days after new dose initiation
When should you take lithium levels (like how often)?
- 2-3 days after initiation
- Then every 1-2 weeks until levels stable
- Once levels stable, every 6-12 months
Sx of mild lithium toxicity
- Fatigue, headache
- Nausea, diarrhea
- Muscle weakness
Sx of moderate lithium toxicity
- Sedation, confusion
- GI upset
- Course tremors
Sx of severe lithium toxicity
- Seizures, coma
- CV collapse
- Death
Describe the steps to take when determining oral lithium dose
1) Calculate creatinine clearance
2) Calculate lithium clearance
3) Calculate maintenance dose using appropriate desired Css
4) Convert mmol to mg
5) Cross check by converting DAILY dose to mmol, then dividing daily mmol dose by lithium clearance to get expected Css and see if its within range
What should you do if you cross check your dose and it comes back below the range?
Cross check another dose; if the new dose if too high then justify the lower dose
Can you ratio lithium doses?
Yes
What should you do if someone is asymptomatic after acute ingestion of a toxic lithium dose?
- Hydrate
- Observe for signs of delayed toxicity
- Serial serum lithium levels recommended
- Monitor volume status, electrolytes, sCr
What should you do if someone is symptomatic (moderate-severe) and you suspect lithium toxicity?
- Refer for immediate medical attention
- Hold lithium
- Dialysis if lithium > 3.5 mmol
What should you do if someone is symptomatic (mild) and you suspect lithium toxicity?
- Refer to MD for evaluation
- Recommend dose adjustment if secondary to non-modifiable cause
