| Identification | Back Directory | [Name]
LITHIUM ION CHROMATOGRAPHY STANDARD | [CAS]
17341-24-1 | [Synonyms]
LITHIUM ION
Lithiumcation
Lithium ion (1+)
Lithium, ion (Li1+)
LITHIUM ION STANDARD
LITHIUM ION CHROMATOGRAPHY STANDARD
LITHIUM, ION CHROMATOGRAPHY STANDARD SOLUTION | [Molecular Formula]
Li+ | [MDL Number]
MFCD00064606 | [MOL File]
17341-24-1.mol | [Molecular Weight]
6.94 |
| Hazard Information | Back Directory | [Definition]
ChEBI: Lithium(1+) is a monovalent inorganic cation, a monoatomic monocation and an alkali metal cation. | [Mechanism of action]
Lithium therapy for disorders is believed to be effective because of its ability to reduce signal transduction
through the phosphatidylinositol signaling pathway. In this pathway, the second
messengers diacylglycerol and inositol 1,4,5-trisphosphate are produced from the enzymatic hydrolysis of
phosphatidylinositol-4,5-bisphosphate (a membrane phospholipid) by the receptor-mediated activation of the
membrane-bound, phosphatidylinositol-specific phospholipase C. The second messenger activity for inositol
1,4,5-trisphosphate is terminated by its hydrolysis in three steps by inositol monophosphatases to inactive
inositol, thus completing the signaling pathway. To recharge the signaling pathway, inositol must be recycled
back to phosphatidylinositol bisphosphate by inositol phospholipid–synthesizing enzymes in the CNS,
because inositol is unable to cross the blood-brain barrier into the CNS in sufficient concentrations to
maintain the signaling pathway. By uncompetitive inhibition of inositol phosphatases in the signaling pathway,
the therapeutic plasma concentrations of lithium ion deplete the pool of inositol available for the resynthesis
of phosphatidylinositol-4,5- bisphosphate, ultimately decreasing its cellular levels and, thereby,reducing the enzymatic formation of the second messengers. Thus, lithium ion restores the balance among
aberrant signaling pathways in critical regions of the brain.
The effects of lithium ion on disorders are surprisingly specific because of the inability of inositol to cross the
blood-brain barrier and replenish depleted inositol levels. Lithium ion exerts its greatest influence on this
signaling pathway when the lithium ion concentration is at saturation conditions.
The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is
characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term
therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and GSK-3
signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and
have been implicated in modulating synaptic function in nerve terminals. | [Pharmacokinetics]
The absorption of lithium is rapid and complete within 6 to 8 hours. The absorption rate of slow-release
capsules is slower and the total amount of lithium absorbed lower than with other dosage forms. Lithium is not
protein bound. The elimination half-life for elderly patients (39 hours) is longer than that for adult patients (24
hours), which in turn is longer than that for adolescent patients (18 hours). The time to peak serum
concentration for lithium carbonate is dependent on the dosage form (tablets, 1–3 hours; extended tab, 4
hours; slow release, 3 hours). Steady-state serum concentrations are reached in 4 days, with the desirable
dose targeted to give a maintenance lithium ion plasma concentration range of 0.6 to 1.2 mEq/L, with a level of 0.5 mEq/L for elderly patients. The risk of bipolar recurrence was approximately threefold greater for
patients with lithium dosages that gave plasma concentrations of 0.4 to 0.6 mEq/L. Adverse reactions are
frequent at therapeutic doses, and adherence is a big problem. Toxic reactions are rare at serum lithium ion
levels of less than 1.5 mEq/L. Mild to moderate toxic reactions may occur at levels from 1.5 to 2.5 mEq/L, and
severe reactions may be seen at levels from 2.0 to 2.5 mEq/L, depending on individual response. The onset
of therapeutic action for clinical improvement is 1 to 3 weeks. Renal elimination of lithium ion is 95%, with
80% actively reabsorbed in the proximal tubule. The rate of lithium ion urinary excretion decreases with age.
Fecal elimination is less than 1%. | [Clinical Use]
For many years, lithium has been the treatment of choice for bipolar disorder, because it can be effective in
smoothing out the mood swings common to this condition. Its use must be carefully monitored, however,
because the range between an effective and a toxic dose is small.Lithium carbonate (Eskalith) is the most commonly used salt of lithium to treat manic depression. Lithium
carbonate dosage forms are labeled in mg and mEq/dosage unit, and lithium citrate (Lithobid) is labeled as
mg equivalent to lithium carbonate and mEq/dosage unit. Lithium is effectively used to control and prevent
manic episodes in 70 to 80% of those with bipolar disorder as well as to treat other forms of depression.
Those who respond to lithium for depression often are those who have not responded to TCAs after several
weeks of treatment. When giving lithium in addition to their antidepressants, some of these people have
shown significant improvement. | [Side effects]
Common side effects of lithium include nausea, loss of appetite, and mild diarrhea, which usually taper off
within first few weeks. Dizziness and hand tremors also have been reported. Increased production of urine
and excessive thirst are two common side effects that usually are not serious problems, but patients with
kidney disease should not be given lithium. Taking the day's dosage of lithium at bedtime also seems to help
with the problem of increased urination. Other side effects of lithium include weight gain, hypothyroidism,
increased white blood cell count, skin rashes, and birth defects.
While on lithium, a patient's blood level must be closely monitored. If the blood level of lithium ion is too low,
the patient's symptoms will not be relieved. If the blood level of lithium ion is too high, there is a danger of a
toxic reaction. | [Drug interactions]
Lithium pharmacokinetics may be influenced by a number of factors, including age. Elderly patients require
lower doses of lithium to achieve serum concentrations similar to those observed in younger adults as a result
of reduced volume of distribution and reduced renal clearance. Lithium ion clearance decreases as the glomerular filtration rate decreases with
increasing age. Reduced lithium ion clearance is expected in patients with hypertension, congestive heart
failure, or renal dysfunction. Larger lithium ion maintenance doses are required in obese compared with
nonobese patients. The most clinically significant pharmacokinetic drug interactions associated with lithium
involve drugs that are commonly used in the elderly and that can increase serum Li+
concentrations. People
who are taking lithium should consult their physician before taking the following drugs: acetazolamide,
antihypertensives, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, calcium
channel blockers, carbamazepine, thiazide diuretics, hydroxyzine, muscle relaxants, neuroleptics, table salt,
baking powder, tetracycline, TCAs, MAOIs, and caffeine. The tolerability of lithium is lower in elderly patients.
Lithium toxicity can occur in the elderly at concentrations considered to be “therapeutic” in the general adult
populations. Serum concentrations of lithium ion need to be markedly reduced in the elderly population—and
particularly so in the very old and frail. |
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