Biomedical uses of Lithium refer to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as mood-stabilizing drugs, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely and in the long term. As a mood stabilizer, lithium is probably more effective in preventing mania than depression, and reduces the risk of suicide in bipolar patients.(Baldessarini et al, 2006) In depression alone (unipolar disorder), lithium can be used to augment other antidepressants . Lithium carbonates (Li2CO3), sold under several trade names, is the most commonly prescribed, while lithium citrate (Li3C6H5O7) is also used in conventional pharmacological treatments. Lithium sulfate (Li2SO4) has been presented as an alternative. Lithium orotate is sometimes marketed as a "safe" natural alternative with fewer side effects than conventional lithium, yet caution must be taken with all of the active lithium salts. Upon ingestion, lithium becomes widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing norepinephrine release and increasing serotonin synthesis.
CONCEPT OF BIOMEDICINE
Biomedicine is a branch of medical science that applies biological and other natural science principles to clinical practice. Biomedicine involves the study of (patho-) physiological processes with methods from biology, chemistry, and physics (Larson, 1998)
CHEMISTRY OF LITHIUM
Lithium is a metallic element that was discovered in 1818. Because it was found in a mineral, it was called ‘lithium’, which is derived from the Greek word lithos, stone. Lithium is identified by the symbol Li on the periodic table at the position number 3 with an atomic mass of 6.94. Lithium is used in a range of industries, typically in the form of alloys and compounds, since it is extremely reactive. Well known lithium applications include the lithium-ion battery and lithium carbonate tablet for treatment of bipolar disorder and mood stabilization(encyclopaedia britanicca,2009)
- Description of Lithium
Chemical element of Group Ia in the periodic table, the alkali metal group, lightest of the solid elements. The metal itself—which is soft, white, and lustrous—and several of its alloys and compounds are produced on an industrial scale. (encyclopaedia britanicca,2009)
- Discovery of Lithium
Lithium was discovered in 1817 by Johan August Arfwedson in the mineral petalite, lithium is found also in economically exploitable quantities in such minerals as spodumene, lepidolite, amblygonite, and petalite; it constitutes about 0.002 percent of the Earth's crust. Chemical treatment of the ores provides lithium hydroxide, carbonate, or sulfate, which can be converted to other compounds. Lithium metal is made by electrolyzing a molten mixture of lithium chloride and potassium chloride.The metal, which can be drawn into wire and rolled into sheets, is softer than lead but harder than the other alkali metals and has the body-centred cubic crystal structure. Lithium and its compounds impart a crimson colour to a flame, the basis of a test for its presence. Lithium floats on water, reacting with it to yield lithium hydroxide (LiOH) and hydrogen gas. It is commonly kept coated with petrolatum because it reacts with the moisture in the air. (encyclopaedia britanicca,2009)
- Isotopes of Lithium
Natural lithium exists as two isotopes: lithium-7 (92.5 percent) and lithium-6 (7.5 percent); five radioactive isotopes have been prepared—lithium-5, lithium-8, lithium-9, lithium-10, and lithium-11—all having half-lives of less than one second. Lithium was used (1932) as the target metal in the pioneering work of John Cockcroft and Ernest Walton in transmuting nuclei by artificially accelerated atomic particles; each lithium nucleus that absorbed a proton became two helium nuclei. The bombardment of lithium-6 with slow neutrons produces helium and tritium. Aluminum, lead, and other soft metals can be made harder by alloying them with small proportions of lithium. (encyclopaedia britanicca,2009)
- Compounds of Lithiun
Lithium is chemically active, readily losing one of its three electrons to form compounds containing the Li+ cation. Many of these differ markedly in solubility from the corresponding compounds of the other alkali metals. A number of the lithium compounds have practical applications. Lithium hydride (LiH), a gray, crystalline solid produced by the direct combination of its constituent elements at elevated temperatures, is a ready source of hydrogen, instantly liberating that gas upon treatment with water. It also is used to produce lithium aluminum hydride (LiAlH4), which quickly reduces aldehydes, ketones, and carboxylic esters to alcohols.Lithium hydroxide (LiOH), commonly obtained by the reaction of lithium carbonate with lime, is used in making lithium salts (soaps) of stearic and other fatty acids; these soaps are widely used as thickeners in lubricating greases. Lithium hydroxide is also used as an additive in the electrolyte of alkaline storage batteries and as an absorbent for carbon dioxide. Other industrially important compounds include lithium chloride, LiCl, and lithium bromide, LiBr. They form concentrated brines capable of absorbing aerial moisture over a wide range of temperatures; these brines are commonly employed in large refrigerating and air-conditioning systems. Lithium fluoride, LiF, is used chiefly as a fluxing agent in enamels and glasses. Of greater significance is lithium carbonate, Li2CO3. Not only is it utilized in the preparation of other lithium compounds but it has been found to be effective in the treatment of the mental disorder manic-depressive psychosis. Organolithium compounds, in which the lithium atom is not present as the Li+ ion but is attached directly to a carbon atom, are useful in making other organic compounds. Butyllithium, C4H9Li, which is used in the manufacture of synthetic rubber, is prepared by the reaction of butyl bromide, C4H9Br, with metallic lithium(encyclopaedia britanicca,2009)
- Properties of Lithium
The atomic number is 3 and the atomic weight is 6.941The melting point is 180.5° C, boiling point is 1,342° C, specific gravity is 0.534 g/cm3 (20° C) ,the valence is 1 and electronic configuration is . 2-1 or 1 s 22 s 1. (encyclopaedia britanicca,2009)
HISTORICAL BACKGROUND OF BIOMEDICAL USES OF LITHIUM
Lithium was first used in the 19th century as a treatment for gout after scientists discovered, at least in the laboratory, lithium could dissolve uric acid crystals isolated from the kidneys. The levels of lithium needed to dissolve urate in the body, however, were toxic.[Marmol,2008] Because of prevalent theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark[ Lenon and Watson, 1994] and William Alexander Hammond in New York[Mitchel, 2000 ] used lithium to treat mania from the 1870s onwards, though use in the form of spring waters to treat mania were reported in ancient Roman and Greek times. By the turn of the 20th century, this use of lithium was largely abandoned, according to Susan Greenfield, due to the reluctance of the pharmaceutical industry to invest in a drug that could not be patented.(Susan, 1999)
As accumulating knowledge indicated a role for excess sodium intake in hypertension and heart disease, lithium salts were prescribed to patients for use as a replacement for dietary table salt (sodium chloride). This practice was discontinued in 1949 when reports of side effects and deaths were published, leading to a ban of lithium sales.( Marmol,2008)
The use of lithium salts to treat mania was rediscovered by the Australian psychiatrist John Cade in 1949. Cade was injecting rodents with urine extracts taken from schizophrenic patients, in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to be psychoactive (adenosine receptors on neurons are stimulated by it; caffeine blocks them), Cade needed soluble urate for a control. He used lithium urate, already known to be the most soluble urate compound, and observed it caused the rodents to be tranquilized. Cade traced the effect to the lithium ion itself. Soon, Cade proposed lithium salts as tranquilizers, and soon succeeded in controlling mania in chronically hospitalized patients with them. This was one of the first successful applications of a drug to treat mental illness, and it opened the door for the development of medicines for other mental problems in the next decades.[ Cade, 1949]
The rest of the world was slow to adopt this treatment, largely because of deaths which resulted from even relatively minor overdosing, including those reported from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmark's Mogens Schou and Paul Baastrup in Europe,( Marmol,2008) and Samuel Gershon and Baron Shopsin in the U.S., this resistance was slowly overcome. The application of lithium in manic illness was approved by the United States Food and Drug Administration in 1970.(Mitchel,2000) In 1974, this application was extended to its use as a preventive agent for manic-depressive illness.
Lithium has become a part of Western popular culture. Characters in Pi, Premonition, Stardust Memories, American Psycho, and An Unmarried Woman all take lithium. Sirius XM Satellite Radio in North America has a 1990s alternative rock station called Lithium, and several songs refer to the use of lithium as a mood stabilizer. These include: "Lithium Lips" by Mac Lethal, "Equilibrium met Lithium" by South African artist Koos Kombuis, "Lithium" by Evanescence, "Lithium" by Nirvana, "Lithium and a Lover" by Sirenia, "Lithium Sunset", from the album Mercury Falling by Sting,(Agassi,1996) "Tea and Thorazine" by Andrew Bird, and "Lithium" by Thin White Rope.
MEDICAL USES OF LITHIUM
Lithium treatment is used to treat mania in bipolar disorder. Initially, lithium is often used in conjunction with antipsychotic drugs as it can take up to a month for it to have an effect. Lithium is also used as prophylaxis for depression and mania in bipolar disorder. It is sometimes used for other psychiatric disorders, such as cycloid psychosis and major depressive disorder.[ Marsh et al, 2006][Alan et al,2007] Lithium possesses a very important antisuicidal effect not shown in other stabilizing medications such as antiseizure drugs.[ Muller et al, 2003] Nonpsychiatric applications are limited; however, its use is well established in the prophylaxis of some headaches related to cluster headaches (trigeminal autonomic cephalgias), particularly hypnic headache. An Italian pilot study in humans conducted in 2005–06 suggested lithium may improve outcomes in the neurodegenerative disease amyotrophic lateral sclerosis (ALS).( Fornai, 2008) However, a randomised, double-blind, placebo-controlled trial comparing the safety and efficacy of lithium in combination with riluzole for treatment of ALS failed to demonstrate a benefit as compared to a combination therapy over riluzole alone.(Aggarwai et al, 2010)
Lithium is sometimes used as an augmenting agent to increase the benefits of standard drugs used for unipolar depression. Lithium treatment was previously considered to be unsuitable for children; however, more recent studies show its effectiveness for treatment of early-onset bipolar disorder in children as young as eight. The required dosage (15–20mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. To prescribe the correct dosage, the patient's entire medical history, both physical and psychological, is sometimes taken into consideration. The starting dosage of lithium should be 400–600mg given at night and increased weekly depending on serum monitoring. Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities, as it interferes with the regulation of sodium and water levels in the body, and can cause dehydration. Dehydration, which is compounded by heat, can result in increasing lithium levels. The dehydration is due to lithium inhibition of the action of antidiuretic hormone, which normally enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine, leading to consequent loss of body water and thirst.( Healy,2005) High doses of haloperidol, fluphenazine, or flupenthixol may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported.(Sandyk, 1983). Lithium salts have a narrow therapeutic/toxic ratio, so should not be prescribed unless facilities for monitoring plasma concentrations are available. Patients should be carefully selected. Doses are adjusted to achieve plasma concentrations of 0.4( Solomon et al,1996) to 1.2mmol Li+/l (lower end of the range for maintenance therapy and elderly patients, higher end for pediatric patients) on samples taken 12 hours after the preceding dose. Overdosage, usually with plasma concentrations over 1.5mmol Li+/l, may be fatal, and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment, confusion, and convulsions. If these potentially hazardous signs occur, treatment should be stopped, plasma lithium concentrations redetermined, and steps taken to reverse lithium toxicity.