Lithium

• uses
• mechanism
• dose and half-life
• adverse drug reactions
• toxicity and overdose
• contraindications and drug interactions
• metabolism and excretion
  

Uses

Very very effective, but dangerous.

• mood stabilizers
• good for combatting suicidal ideation

 

Mechanism

 

 

Dose and Half Life

• dose is very important: too low and there will be little effect; too high and lithium toxocity can be fatal

Begin at 300 mg, assess levels, and then move it up after 5 days.

Dosing is 600-1800 mg/day; aim for serum levels of 0.8-1.1 mmol/L for adults and 0.4-0.6 mmol/L

• follow in one month, then every three months

Monitoring Lithium Therapy

baseline labs: renal functioning, TSH

obtain serum levels 5 days after the most recent dose titration, 12 h after the dose. Once at a effective dose, follow bloodwork for a few weeks, then move to testing every 3 months or so.

ECG

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Adverse Drug Reactions

Lithium toxicity is bad news: follow lithium blood levels and drink lots of water.

 

CNS: fatigue, dysphoria, fine tremor

GI: nausea, vomiting, diarrhea, weight gain

CVS: benign T wave changes, sinus

Nephrotoxicity

can damage kidneys (1:500-1:1000)

Lithium collects in the collecting tubules, where it can lead to ADH resistance. This should be avoided in combination with other drugs causing volume depletion or which prevent the kidneys from compensating.

Chronic interstitial nephritis can occur in 15-20% of long term users of lithium.

Nephrotic syndrome (minimal change disease or focal segmental glomerulosclerosis can occur.

Renal tubular acidosis can follow reduced activity of H+ ATPase in collecting tubule.

endocrine: hypothyroidism, hypoparathyroidism

Other symptoms include cognitive impairment, tremor, acne, psoriasis, polydypsia, polyuria, edema, nausea and vomiting.

benign leukocytosis

4-12% rate of congenital malformations: Epbstein anomaly, polyhydramnios, preterm delivery

 

Lithium Toxicity and Overdose

Toxicity is usually chronic, though acute overdose is always possible. Precipitants include renal failure or dehydration.

• mild (1.5-2.5 mEq/L) 
• moderate (2.5-3.5 mEq/L) 
• severe (>3.5 mEq/L)

manifestations include:

• CNS: confusion, drowsiness, acute delerium, hallucinations, ataxia, slurred speech, seizures, coma
• neuromuscular: coarse tremor, hyperreflexia, fasciculations, rigidity, weakness
• CV: irregular pulse, increased or decreased BP
• GI: nausea and vomiting, diarrhea
• other: extrapyramidal symptoms, catatonic stupor, leukocytosis, hypercalcemia, renal failure

Treatment includes supportive measures, hypotonic IV, and hemodialysis if levels are over 4 or with significant symptoms

 

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Counter-Indications and Drug Interactions

• [Li] is dependent on GFR; make sure you know what you're doing
• [Li] increases with NSAIDs, Cox-2 inhibitors
• hydrochlorothiazide diuretics can cause lithium toxicity
• indapamide (furosemide)
• ACE inhibitors, ARBs
  • if diuretics are needed, decrease lithium by 50% prior to starting, then adjust dose based on levels over coming days
• decreased salt and fluid intake can affect [Li]
• caffeine, mannitol, increased sodium intake decrease levels

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Metabolism and Excretion

• almost completely through kidneys

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