What is Lithium clearance?
0.25 x CrCl
What is the conversion factor of Li between mEq and mg?
0.12mEq/300mg
How many days until the steady state of Li is reached?
3-5 days
What is the bioavaliability (F) of Li?
1
How is Li distributed?
not protein bound, evenly distributed in total body water
When is the Cmax of Li?
- IR= 1-3hrs
- SR= 4-6hrs may be up to 12hrs in OD
How is Li excreted?
unchanged in urine, approx 75-80% reabsorbed
What is the half life of Li?
~20hrs, treatment duration increases t1/2 by 40-50%
Where in the glomerulus is Li reabsorbed?
70-80% in the proximal tubule
Where can Li bind in the glomerulus?
sodium-dependent co-transporter sodium channel (ENaC) and Na/H exchanger
Li binds over Na causing excess Na loss
What may occur with long-term use of Li?
NDI
How does long-term Li use result in NDI?
inhibits cAMP formulation and promotes lack of ADH = lose ability to reabsorb water
What is the treatment of NDI?
amiloride
What are the factors that increase Li clearance?
- Na loading
- pregnancy
- acute mania
- daytime dosing
- drug interactions
What are the factors that decrease Li clearance?
- advance age
- drug interactions
- renal impairment
- dehydration
- Li use > 1 year
- nighttime dosing
At what renal clearance should Li be avoided?
CrCl < 30 mL/min
What is the initial dosing of Li for acute mania?
300-600BID-TID
What is the typical dosing range of Li?
900-2400 mg/day
What is the positive of simplifying the Li dosing regimen to once a day dosing?
less polyuria and reduced renal concentration capacity
What factors can affect measured drug levels of Lithum?
- dosing schedule variations/adherence
- preparation
- crash diets/changes in salt intake
- renal function
- hydration status
- interacting meds
What is the result of volume depletion with Li use?
volume depletion due to illness/conditions= decreased renal diffusion= increased proximal tubule Na reabsorption= increased Li reabsorption= risk of TOXICITY
What diuretic may be used safely with Li?
loops
What are the drug interactions of Li?
- ACE/ARB= Na depletion, Li retention= increased Li levels= risk of toxicity
- NSAIDs= decreased renal blood flow, increased tubular reabsorption= decreased Li clearance= increased Li levels= risk of toxicity
Which NSAIDs are associated with the highest risk of Li toxicity?
indomethacin, ibuprofen, naproxen
