Symbol: Li Atomic No: 3Lithium
Importance in Man of Lithium
Useful modulating ion in mania
Web Resources for Lithium
Relevant Clinical Literature
- In Roman times alkaline springs were used in the treatment of mania
- Used medicinally in the 19th century as a treatment for gout
- As lithium carbonate and citrate, forming part of alkaline salt mixtures in widespread use.
- Lithium concentrations low, typically 3 to 26 mmol and some reports of psychiatric effects
- Experiments in the early part of the 20th century to treat hypertension and heart failure as a substitute for salt lead to fatalities and was quickly abandoned
- John Cade serendipitously discovered that it had a calming effect in 1948 at higher doses
- Although he reported this in 1949 leading to a revolution in psychiatric practice outside the USA. It was not until 1970 that the FDA licensed its use. Reasons for this were that it could not be patented and had an unattractive therapeutic index.
Mechanism of action
- Directly inhibits, in a non-competitive fashion, the activity of glycogen synthase kinase-3(GSK-3, GSK-3β) so activating the Wnt pathway
- Alters phosphoinositide (PI) turnover
- Acts on Akt-mediated signalling pathway, with alterations in gene transcription.
Lithium is used as a mood-stabiliser in bipolar disorder.
Pharmacokinetics and pharmacodynamics
It may be an essential element in man but this is unknown.
- The dose is hard to predict and the concentration achieved may vary according to changes in climate, hydration and renal function and at random. The thyroid may be adversely affected - the incidence of hypothyroidism in those taking Lithium is 8-15 times that in those not.
- Regular measurement of serum lithium and of renal and thyroid function tests are required. In a stable patient this may be every 2-3 months. Men and young women are less likely to develop thyroid abnormality and perhaps need TFT monitoring every 6-12 months.
- Because of different plasma and intracellular kinetics patients may be toxic with levels in the therapeutic range (0.6 to 1.2 mmol/L).
- Handled like sodium in proximal tubules so sodium depletion can enhance re-absorption and precipitate toxicity
- Dialysis treatment of choice for severe toxicity
- Other Manifestations
- Standard salts: peak serum levels in 2 - 3 hours and gastrointestinal absorption complete within 8 hours
- Sustained-release: peak serum levels in 6 to 24 hours
- Slower total body distribution and delayed onset of action (crosses cell membranes slowly)
- 6 -10 days required for total body equilibrium.
- Slow elimination from cells (t1/2 24 ±12 hours)
- Elimination effectively renal
- Dependent upon:
- Glomerular filtration rate
- Renal tubular re-absorption
- Thus elimination t1/2 is 12 hours odd initially and increases to order 22 hours after several weeks of treatment
- Markedly altered by:
- Changes in diet (salt intake)
- Renal function
- Care with physiological aging
- Drugs that impair renal function
- NSAIDs also increase re-absorption in the proximal tubules
- Cardiac output
- ↑ lithium levels
- ↓ lithium levels (increase urinary excretion)
- Enhance toxicity
- ↑ Amdisen A. Clinical features and management of lithium poisoning.Med Toxicol Adverse Drug Exp. 1988;3(1):18-32
- ↑ Cade, JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949;36:349-352
- ↑ Hall AC, Brennan A, Goold RG, Cleverley K, Lucas FR, Gordon-Weeks PR, et al. Valproate regulates GSK-3-mediated axonal remodeling and synapsin I clustering in developing neurons. Molecular and cellular neurosciences 2002;20:257-70.
- ↑ Detera-Wadleigh SD. Lithium-related genetics of bipolar disorder. Annals of medicine 2001;33:272-85.
- ↑ http://www.jr2.ox.ac.uk/bandolier/band74/b74-6.html