Serum levels of lithium

Sedvall, G., Petersson, U., and Fyro, B., Individual differences in serum levels of lithium in human subjects receiving fixed doses of lithium carbonate. Relation to renal lithium clearance and body weight. Pharmacol. Clin. 2, 231-235 (1970). 

J.E, Cole, K., and Lavelle, J. (1998) Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med 321 1489-1493. 

Perils RH, Sachs GS, Lafer B, et al Effect of abrupt change from standard to low serum levels of lithium a reanalysis of double-blind lithium maintenance data. Am J Psychiatry 159 1155-1159, 2002... 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Because no antidote is available, treatment is supportive. A patient s condition should be monitored closely, including fluid intake and output, mental status, and serum levels of lithium, creatinine, and electrolytes. Patients with normal renal function should be able to clear lithium unassisted. If necessary, attempts should be made to remove excess lithium from the body by gastric lavage and emesis. 

Vollhardt M, Ferbert A. [Influence of hypocalcemia and high serum levels of lithium on the amplitude of N20/P25 components of median nerve SEP.] EEG-Labor 1999 21 65-70. 

Serum levels of lithium can be decreased by as much as 20-30% when theophylline is combined with lithium. 

Not understood. A paper that plotted the serum levels of lithium and carbamazepine on a two-dimensional graph failed to find any evidence of synergistic toxicity. Sinus node dysfunction can be caused by either lithium or carbamazepine, but this is rare. However, the effects may possibly be additive. 

A carefully monitored single case (51 ) has documented the relationship of maternal to foetal lithium levels in a woman treated with lithium for the second and third trimester of pregnancy. The close similarities in maternal, umbilical and neonatal lithium levels confirm the absence of a placental barrier. Minor vomiting occurred in the infant until 1 week after delivery when the serum levels of lithium had fallen to below 0.2 mEq/1. 

Absorption/Disthbution - Lithium is readily absorbed from the Gl tract. Peak serum levels occur in 0.5 to 3 hours and absorption is complete within 8 hours. Onset of action is slow (5 to 14 days). Until the desired therapeutic effect is attained, maintain a steady-state serum level of 0.8 to 1.4 mEq/L, then slowly decrease the lithium dose to a maintenance level. The therapeutic serum level range is from 0.4 to 1 mEq/L. 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

Simhandl C, Denk E, Thau. The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders. J Affect Disord... 

When a specific antidote or other treatment is under consideration, quantitative laboratory testing may be indicated. For example, determination of the acetaminophen serum level is useful in assessing the need for antidotal therapy with acetylcysteine. Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and other drugs and poisons may indicate the need for hemodialysis (Table 58-3). 

Several processes in the immune response are affected by lithium in vivo and in vitro 139). The proliferative responses of hamster lymphoid cells to concanavalin A or phytohemagglutinin, which stimulate mitosis in T cells, were enhanced by lithium in a serum-free culture system. Proliferative stimulation also was obtained with lithium using the B cell mitogen lipopolysaccharide, but the B cell mitogens dextran sulfate and trypsin had no effect 140-143). Lithium increased the effects of suboptimal concentrations of stimulants, but had smaller effects on stimulation by optimal concentrations. With concanavalin A, the response to optimal stimulatory concentrations was inhibited 140). Paradoxical results such as these may be due to inhibitory effects of lithium on adenylate cyclase, or to effects on membrane transport systems 141). Most of these experiments used very high concentrations of lithium, considerably in excess of normal therapeutic doses (maximal inhibitory concentrations were 10 mM with hamster cells and 5 mM with human lymphocytes). At therapeutic levels of lithium, increased incorporation of [ H]thymidine was seen in human peripheral blood mononuclear cells. 

Lithium affects thyroid function (52-56), and in most patients, after 4 months of treatment, there is a transient fall in serum levels of thyroxine (T4) and a rise in thyrotropic hormone (thyroid-stimulating hormone, TSH). After 1 year of treatment, these hormones have generally returned to their baseline. The mechanisms for this are obscure, but lithium inhibits both thyroxine synthesis and its release from the gland (201). Lithium may inhibit endocytosis in the thyroid gland, which results in an accumulation of colloid and thyroglobulin within the follicles, thereby reducing hormone release (202). Thyroid volume... 

Recent extensive reviews describe current indications for lithium therapy primarily in bipolar disorders and experimentally in unipolar depression as well as schizo-affective schizophrenia, alcoholism, premenstrual cramps and character disorders. These reports also call attention to the narrow therapeutic index associated with its use and the need for careful moniterlng of serum levels. Serum levels of 0.6 to 1.5 mEq per liter are usually sufficient for management of symptoms. A dose of 300mg of lithium carbonate t.i.d. or q.l.d. is recommended to maintain these... 

In 9 out of 10 healthy subjects alcohol 0.5 g/kg raised the serum levels of a single 600-mg dose of lithium carbonate by 16%. Four subjects had at least a 25% increase in lithium levels. However these rises were not considered to be clinically important. In contrast a study in 20 healthy subjects given lithium carbonate (to achieve lithium serum levels of... 

Other studies confirm that normal therapeutic levels of lithium carbonate reduce plasma chlorpromazine levels.The peak serum levels and AUC of chlorpromazine were reduced by 40% and 26%, respectively, in healthy subjects given lithium carbonate. ... 

Not understood. One suggestion to account for the reduced serum levels of chlorpromazine, which is based on animal studies, is that chlorpromazine can be metabolised in the gut. Therefore, if lithium delays gastric emptying, more chlorpromazine will be metabolised before it reaches the circulation. Just why severe neurotoxicity and other adverse effects sometimes develop in patients taking lithium and antipsychotics is not understood. It is the subject of considerable discussion and debate. ... 

A patient with systemic lupus erythematosus suffering from steroid-induced depression and moderate renal impairment was given lithium 600 mg daily and her depression improved. However, serum-lithium levels increased from 0.4 to 0.8 mmol/L within one week and the lithium treatment caused an exacerbation of a finger tremor. The lithium was discontinued and then restarted at 400 mg daily, resulting in serum levels of 0.4 mmol/L, which improved her depression and was associated with only a fine finger tremor. Three other patients with steroid-induced depression were also successfully treated with lithium. ... 

Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L (Table 32-1). Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results. 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

An initial examination of the extent to which lithium may prevent cannabis withdrawal in rats was conducted by Cui et al. (2001), who reported that, at clinically relevant serum levels, lithium prevented the appearance of the cannabis withdrawal syndrome. The authors also noted that these effects were accompanied by a release of oxytocin, which they conclude is responsible for suppression of the withdrawal signs. 

In a study of psychiatric patients after 1 week of lithium treatment, the serum Li+ level was typically 1 mM, whereas in brain and muscle the levels were 0.4 and 0.5 mM, respectively. Within the brain itself, the distribution of Li+ appears to be uneven however no particular region appears to accumulate Li+ to any significant extent [47]. It has been... 

Lithium toxicity can occur with serum levels greater than 1.5 mEq/L, but the elderly may have toxic symptoms at therapeutic levels. Severe toxic symptoms may occur with serum concentrations above 2 mEq/L, including vomiting, diarrhea, incontinence, incoordination, impaired cognition, arrhythmias, and seizures. Permanent neurologic impairment and kidney damage may occur as a result of toxicity. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

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