Lithium

The mechanism of action of lithium is not known. It is rapidly absorbed, has a small volume of distribution, and is excreted in the urine unchanged (there is no metabolism of lithium). The half-life of Lithium is 18 to 30 hours. Absorption is lower on an empty stomach [8].

Adverse effects
Lithium can cause several adverse effects. Normally the side effects are dose-related [8]. Notable side effects include:

• Cardiac: Bradycardia, flattened or inverted T waves, heart block, and sick sinus syndrome [8].
• CNS: Confusion, memory problems, new or worsening tremor, hyperreflexia, clonus, slurred speech, ataxia, stupor, delirium, coma, and seizures (rarely). These effects are theoretically due to excess action on the same sites that mediate therapeutic action [8].
• Renal: Nephrogenic diabetes insipidus with polyuria and polydipsia. These side effects are due to lithium's action on ion transport [8]. Long-term lithium treatment is associated with end-stage renal disease. There is however little evidence of a clinically significant reduction in renal function in most patients, but the results do suggest that lithium treatment requires continuous monitoring of kidney function [9].
• Hematologic: Leukocytosis and aplastic anemia [8].
• Gastroenterologic: Diarrhea and nausea [8].
• Endocrinal: Euthyroid goiter or hypothyroid goiter [8].
• Other: Acne, rash, and weight gain. Lithium-induced weight gain is more common in women than in men [8].

Lithium modifies sodium transport in nerve and muscle cells. It alters the metabolism of neurotransmitters, specifically catecholamines, and serotonin. It may alter intracellular signaling via second messenger systems by inhibition of inositol monophosphate. This inhibition, in turn, affects neurotransmission through the phosphatidylinositol secondary messenger system [8].

Lithium is known to impair thyroid function. This is a common side effect of lithium medication. However, a study also shows that naturally low concentrations in drinking water in some cases may be sufficient for affecting the thyroid function. This is critical, as hypothyroidism, a condition in which the thyroid gland is incapable of producing enough thyroid hormones, has been associated with increased risk of gestational hypertension, placental abruption, preterm delivery and fetal loss. Also, it has been associated with lower birth weight, congenital hypothyroidism, and impaired neurological function [12].

Another study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results substatiates the need for control of lithium in drinking water, including bottled water [10].

Lithium decreases protein kinase C activity which alters genomic expression associated with neurotransmission [8].

Lithium is thought to increase cytoprotective proteins and possibly activates neurogenesis and increases gray matter volume [8].