Lithium

Half life

18-30 hours

Drug Interactions with Lithium

Antipsychotics - May be used with DRA safely, however if administered in high doses may increase EPS symptoms. Antidepressants - Occasional reports of Serotonin Syndrome Anticonvulsants - No interactions with carbamazepine or valproate. NSAID's - May reduce renal lithium clearance Diuretics - Thiazides - reduce renal lithium clearance which increases toxicity. K+sparing diuretics - may increase lithium concentration, Loop (laxis) - ***Lithium clearance unchanged ACE inhibitors - reduced lithium clearance CA+ inhibitors - neurotoxicity Propranolol - used for lithium tremor. Possible slight increase in lithium concentration.

Tests

Before initiating treatment, kidney function tests, including creatinine and urine specific gravity and thyroid function tests, electrocardiogram for patients over 50. Repeat kidney function tests 1-2 times per year.

Management of Lithium Toxicity

Discontinue lithium and treat dehydration! Obtain lithium level, P-8, renal function tests, and EKG Acute ingestion - residual gastric contents should be removed by induction of emesis, gastric lavage, and polystyrene sulfonate (Kayexalate) or Golyletly. Vigorous hydration > 4.0 mEqu/L lithium level/severe toxicity = hemodialysis

Signs and symptoms of Lithium Toxicity

Early signs and symptoms of lithium toxicity: (lithium level 1.5-2 mEq/L) GI: V/D/N, abdominal pain, dryness of mouth Neurologic symptoms: Ataxia, tremor, dizziness, slurred speech, nystagmus, lethargy or excitement, muscle weakness. Moderate to severe intoxication: (lithium level 2-2.5 mEq/L) GI: A/N/V - persistent Neurologic symptoms: Blurred vision, clonic limb movements, convulsions, delirium, EEG changes, stupor, coma, cardiac failure Severe lithium intoxication (lithium level > 2.5 mEq/L) Generalized convulsions, oliguria, renal failure and death! General Pearls about Lithium Toxicity: Risk factors for toxicity includes exceeding the recommended dosage, renal impairment, low-sodium diet, drug interactions, and dehydration. Elderly are more vulnerable. The higher the lithium level (concentration) the worse the s/s of toxicity will be. Lithium Toxicity = Medical emergency

Proposed mechanism of action of Lithium

Exact MOA is not clear, lithium has been thought to alter ionic activity and the activities of neurons. Inhibits dopamine, NE synthesis and release Increases serotonin synthesis and release. Inhibits the phosphatidylinositol cascades in the brain. More recent studies suggest that lithium may inhibit the action glutamate, an excitatory NT in the synapse.

Therapeutic plasma levels

For acute mania treatment 1.0-1.5mEq/L, for maintenance treatment 0.4 to 0.8 mEq/L.

Lithium adverse effects

Greater than 80 of patients taking lithium experience side effects. Neuro: Lack of spontaneity, memory difficulties, tremor, ataxia, irritability. seizures,mild parkinsonism, dysarthria Endocrine: Goiter, hypothyroidism, exophthalmos, hyperthyroidism CV: Benign T-wave changes (flattening or inversion) resemble s/s of hypokalemia on EKG. Renal: Concentrating defect, polyuria, polydipsia, DI, reduced GFR, nephrotic syndrome Thryoid effects: Hypothryoidism especially in women. Check TSH every 6-12 months. Patient who develop rapid cycling > risk of developing. Treatment = Levothyroxine (Synthroid) Treatment may involve fluid replacement, lowest effective dose of lithium and thiazide or potassium sparing diuretic. If diuretic is used, cut lithium dose in half, and start diuretic in 5 days. Derm: Acne, hair loss, psoriasis, rash, and alopecia. GI: Appetite loss, N/V/D, weight gain, fluid retention (divide doses, take with food or switch to different preparation to reduce GI effects). Lithium citrate less likely to cause diarrhea. ****Excessive Na+ intake = lower lithium concentrations. Low NA+ intake = Can lead to potentially toxic concentrations of lithium.

How long until it works

Lithium exerts anti-manic effects over 1-3 weeks.

Commonly prescribed for

Lithium is used for acute-phase illness as well as for prevention of recurrent manic and depressive episodes. Manic episodes of bipolar disorders, maintenance treatment for manic depressive patients with a history of mania, bipolar depression, major depressive disorder, vascular headache, & neutropenia. Lithium provides more effect prophylaxis for mania than for depression. Lithium is not more effective than antidepressants. Used in depressed patients who have failed to respond to antidepressants alone. Effective treatment for persons with severe cyclothymic disorder. Lithium reduces the incidence of suicide in persons with bipolar I disorder 6-7X's.

Lithium levels

Lithium levels should be obtained every 2-6 months except when signs of toxicity are present. Baseline ECG should be obtained annually.

Class

Mood Stabilizer

Lithium Pharmokinetics

Onset - 5-7 days Peak - 10-21 days Duration - variable *** Patients should do better in about 2-3 weeks.

Pharmacologic Actions

Rapidly absorbed after oral administration. Standard concentration peaks in 1-1.5 hours, slow release - 4-4.5 hours. Lithium does not bind to plasma proteins, is not metabolized and is excreted through the kidneys. The elimination half life of lithium is 18-24 hours. Obesity is associated with higher rates of lithium clearance. Lithium excretion increases during pregnancy, and is excreted in breast milk.

Risk category when use with pregnant women

Risk category D Do not administer to pregnant women in the 1st trimester because of the risk of birth defects. Most common CV defect is Ebstein's anomaly of the tricuspid valves.

How to dose

Start 300mg TID (regular release formulation)and adjust dosage upward as indicated by plasma lithium levels. Acute usual dosage range 1800mg/day in divided doses Maintenance usual dose 900-1200 mg/day in divided doses. Elders and elderly with renal impairment dosage should be 300 mg once or twice daily. **** Divided doses reduces gastric upset and avoids single high peak lithium concentrations.

How to stop

Taper gradually over 3 months to avoid relapse, rapid discontinuation increases the risk of manic and depressive episodes and possibly suicide.

Patient and Family Teaching

Teach patient s/s of lithium toxicity, factors that may affect lithium level, & lab testing. Excessive sweating, intense exercise, use of ACE inhibitors, NSAIDS can disrupt lithium levels. Advise patient not to stop taking their medication.

What medications may lower plasma lithium concentration?

acetazolamide, alkalizing agents, xanthine preparations, osmotic and loop diuretics and urea may lower lithium plasma concentrations.

What medications may increase plasma lithium concentrations?

ibuprofen, diuretics, angiotensin-converting enzymes, methyldopa, carbamazepine, and phenytoin, diuretics, & ACE inhibitors

Interaction with ibuprofin or non-steroidal anti-inflammatory agents may

increase plasma lithium concentrations