Lithium

Lithium 화학적 특성, 용도, 생산

• 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.

• 부작용

  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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