Lithium

Question 1

What is the most frequently used salt formulation of Lithium?

Answer 1

Lithium carbonate
-dosages are listed as mmol equivalents of lithium carbonate
-300 mg lithium carbonate = 8.12 mmol Li = 8.12 meq Li

Question 2

Equivalent to Lithium citrate solution

Answer 2

5 ml = 8 mmol Li = 8 meq Li

Question 3

How long does it take for the drug to be distributed in the body?

Answer 3

ß-distribution phase can take up 6-10h

Question 4

When should lithium serum concentration be obtained after administration of Lithium?

Answer 4

No sooner than 12 hours
-to avoid falsely high peak concentration
-advise patients to take their dose at bedtime

Question 5

What is the therapeutic range of Lithium?

Answer 5

0.6 - 1.2 mmol/L (obtained 12h after last dose)

-Acute mania: 0.8 - 1.2 mmol/L
once the mania has subsided -> maintenance
-Mainetnance: 0.6 - 1.2 mmol/L

Question 6

Counseling points

Answer 6

-take it at bedtime if possible
-take as direct and always for 2-3 days before levels drawn
-report any issues in adherence and blood samples
-take with food to avoid GI/CNS side effects

Question 7

Short-term ADR

Answer 7

Muscle weakness
Lethargy
Polydipsia and polyuria
Headache
Tremor (shorter dosage interval to decrease peak
levels, decrease dose or add in a beta-blocker)

Question 8

Long term ADR

Answer 8

Diabetes insipidus
Renal toxicity (up to 20%)
Hypothyroidism
EKG changes
Weight gain
Leukocytosis
Dermatologic effects

Question 9

Labs to consider before starting Lithium

Answer 9

-Basic Metabolic Panel (electrolytes and serum creatinine)
-Complete blood count with differential
-Thyroid function tests
-Urinalysis (osmolality and specific gravity)
-Urine drug screen
-EKG
-Pregnancy test

Question 10

When should Lithium serum concentration levels be checked?

Answer 10

-every 2-3 days if there is risk for toxicity

-at steady state: recheck levels every 1-2 weeks for 2 months

-check within 1-2 weeks if the dose has changed or a DDI-drug has been added

-during maintenance therapy: every 3-6 months (1-2 months if mood is not stable, 6-12 months if stable)

-recheck after acute maniac episodes (increased clearance during episodes)

Question 11

How is Lithium cleared?

Answer 11

-95% unchanged in the urine
-80% reabsorbed

-clearance = average 25% of creatinine clearance
-oral bioavailability = 100%

peak concentration:
-lithium citrate syrup: 15-30 min (causes N/V)
-Rapid-release tablets/capsule: 1-3h
-sustained-release tablets: 4-8h

Question 12

Vd and half-life

Answer 12

-Vd = 0.7L/kg

-T1/2:
alpha distribution: 6h
beta elimination: 20h

Question 13

Lithium in pregnant women

Answer 13

-avoid during pregnancy
-crosses the placenta (similar concentration in maternal)
-levels in breast milk are 35-50% of maternal serum

Question 14

When is the clearance of Lithium increased?

Answer 14

-During the day (circadian rhythm): 30%
-during manic episodes: 50%

-Clearance: 20 ml/min

Question 15

How does sodium affect lithium concentration?

Answer 15

Lithium is reabsorbed in the same way as sodium (Li follows Na)

increase in sodium reabsorption
-dehydration
-sodium-restricted diet

increased clearance
sodium loading
manic episodes
pregnancy (but not used during pregnancy)

Question 16

Drugs interacting with Lithium

Answer 16

-NSAIDs: decrease clearance and increase concentrations, decrease in renal blood flow via inhibition of prostaglandin -> use sulindac or aspirin

-thiazides: cause sodium depletion -> sodium reabsorption at the proximal tube -> lithium reabsorption decreased by 50%

-loops: (weak evidence)

-Theophylline and Caffeine: decrease in clearance by 58%

-ACE/ARBs: may increase concentration by 200% - 300% AVOID!

Question 17

Which diuretic to choose when Litihium is used?

Answer 17

Amiloride (minimal effects)