Anesthesia Related (I read this and it seems reasonable): "there are several considerations which one must be aware of when providing anesthesia to patients receiving lithium therapy: potential prolongation of neuromuscular blockade (established for succinylcholine and pancuronium; not studied for the newer agents); possible potentiation of the action of sedative/hypnotics (established for barbiturates and diazepam; not studied for propofol, midazolam, or other newer agents); potential cardiac arrhythmias and conduction abnormalities (documented in lithium toxicity; one case report of atropine-resistant bradycardia during anesthesia with propofol and fentanyl); and the possibility of hypothyroidism and nephrogenic diabetes insipidus precipitated by the lithium therapy."
http://www.sambahq.org/professional-...lith-stop.html



ALSO

Classification:
Psychotropic Agents
Antimanics

Description: Lithium is a monovalent cation similar to sodium and potassium. For clinical use, it is administered orally as the carbonate and the more water-soluble citrate salts. Lithium is the drug of choice in treating recurrent bipolar affective disorder (i.e., manic-depressive illness) and has also been used for unipolar disorder (depression). Nonpsychiatric uses of lithium include the syndrome of inappropriate secretion of ADH (SIADH), neutropenia, thyrotoxic crisis, and migraine and cluster headaches, although these are not FDA-approved uses. The use of lithium in clinical medicine dates back to 1841 when it was proposed to be an effective therapy for gout, but it was later found ineffective for this purpose. In the late 1940s, lithium chloride was used as a salt substitute. After several cases of lithium toxicity were associated with indiscriminate use, it was withdrawn from the market until 1949 when it was serendipitously discovered that lithium was beneficial in the management of mania. Lithium carbonate was approved by the FDA in 1970. The pharmacokinetics of the drug were not well understood until years later.

Mechanism of Action: Lithium competes at cellular sites with sodium, potassium, calcium, and magnesium ions. Lithium competes with these ions at intracellular binding sites, at protein surfaces, at carrier binding sites, and at transport sites. At the cell membrane, lithium readily passes through sodium channels, and high concentrations can block potassium channels. Although the mechanism of the antimanic and antidepressant action in the CNS is not known, evidence suggests that the drug interferes with the synthesis, storage, release, and reuptake of monoamine neurotransmitters. Lithium enhances the uptake of tryptophan, increases the synthesis of serotonin, and may also enhance the release of serotonin in the CNS. Lithium does not possess sedative, depressant, or euphoriant effects. Onset of the acute antimanic effect is usually seen in 5—7 days, and the full therapeutic effect is established in 10—21 days.

Lithium administration increases renal sodium and potassium clearance. These effects are attenuated by a compensatory increase in aldosterone after 2—3 days. Lithium does not affect sodium reabsorption in either the ascending limb of the loop of Henle or in the distal tubule. A decrease in renal concentrating ability occurs in 30—50% of patients while receiving lithium; it often produces a mild nephrogenic diabetes insipidus manifested as polyuria. Lithium-induced diabetes insipidus is thought to be due to inhibition of vasopressin-induced adenylate cyclase activity in the medullary collecting tubule of the nephron. Since lithium is more toxic and a less reliable agent than demeclocycline, lithium should be considered a last choice for the treatment of SIADH.

Lithium enhances granulocyte production via stimulation of monocyte colony stimulating factor production. Lithium produces an increase in the total neutrophil pool and each of its components in the bone marrow and circulation. Leukocytosis peaks within 7—10 days of initiating therapy and the WBC count will return to baseline 7—10 days after discontinuing lithium.[737]

The actions of lithium on the heart generally give rise to adverse (i.e., not therapeutic) effects. The most common EKG changes include flattening or inversion of the T-waves. This manifestation is thought to be due to lithium-induced inhibition of potassium cellular reuptake leading to intracellular hypokalemia. Because lithium displaces potassium, an extracellular hyperkalemia is seen and, since the intracellular:extracellular potassium balance is shifted, cardiac arrest is possible at lower than usual degrees of hyperkalemia.

Pharmacokinetics: Lithium salts are administered orally. Lithium is rapidly absorbed from the GI tract, and the rate of absorption is not significantly slowed by the presence of food. Lithium carbonate in tablets or capsules is 95—100% absorbed. Bioavailability from slow-release lithium carbonate tablets is 60—90%. Lithium citrate oral solutions are essentially 100% absorbed. Lithium carbonate is most commonly used because it has a longer shelf-life and contains more lithium on a weight basis than do other salts.

Peak serum concentrations after administration of lithium carbonate rapid-release formulations are reached in 0.5—3 hours, and absorption is complete within 6 hours. When extended-release tablets are used, peak lithium concentrations are observed 4—12 hours after the dose. Oral solutions of lithium citrate are extremely rapidly absorbed; peak serum levels are achieved in 15—60 minutes. Lithium has negligible protein binding and is distributed throughout the body, with slightly greater concentrations in thyroid, bone, and brain tissue. It is excreted unchanged in urine. A 300 mg dose of lithium carbonate tablets produces peak serum concentrations of 0.4—0.5 mEq/L. A similar dose in capsules gives peak serum concentrations of 0.4—0.9 mEq/L. Serum lithium concentrations tend to fluctuate for 6—10 hours after dosing, so the 12-hour post-dose serum concentration is used for monitoring purposes. Data published in 1989 confirmed that serum concentrations of 0.8—1 mEq/L are more effective in preventing relapse in patients with bipolar disorder than are lower concentrations of 0.4—0.6 mEq/L.[17] Steady-state serum lithium concentrations of 1—1.5 mEq/L are required to control acute mania. Toxicity is likely in most patients when levels exceed 1.5 mEq/L, although symptoms of lithium toxicity can appear in some patients with serum concentrations of 1 mEq/L or less. The narrow therapeutic ratio and interpatient variations make individual monitoring and dosage adjustment essential.

Approximately 90—95% of a dose of lithium is eliminated by the kidneys. The amount eliminated through sweat, saliva, and feces is negligible under normal circumstances. Lithium is freely filtered by renal glomeruli, but it also undergoes significant renal tubular reabsorption. Thus, any decrease in GFR will reduce lithium elimination. It was once thought that tubular reabsorption occurred only in the proximal tubule but interaction studies with HCTZ and furosemide revealed substantial lithium reabsorption also occurs in the ascending limb of the loop of Henle.[1202] In patients with normal renal function, biphasic elimination is observed. The initial half-life is 0.8—1.2 hours, and the terminal half-life is approximately 20—27 hours, although reported half-life values have ranged from 5—79 hours. In young adults, the half-life is 18—24 hours, and in the elderly, it is 30—36 hours. Many factors can affect lithium clearance including hyponatremia or hypernatremia, dehydration, and diuretic use.

References
17. Gelenberg AJ, Kane JM, Kekller MB et al. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med 1989;321:1489—93.

737. Lee M, Hopkins LE. Attenuation of chemotherapy-induced neutropenia with lithium carbonate. Am J Hosp Pharm 1980;37:1066—71.

1202. Jefferson JW, Kalin NH. Serum lithium levels and long-term diuretic use. JAMA 1979;241:1134—6.


Drug Information Provided by
Gold Standard Inc. � 2007