Plasma lithium

In contrast to the limited value of pharmacokinetics to the use of antidepressants, knowledge of the kinetics of lithium has been important in defining the therapeutic and toxic range in unipolar or bipolar manic patients. Prediction of the dose required by the individual patient by giving a single dose of the drug and measuring the erythrocyte/plasma lithium... 

Add lithium to a standard antidepressant (e.g. an SSRI) maintaining the plasma lithium concentration at 0.4-0.6mmol/l. This is a well-established method with approximately 50% of the patients responding. However, the plasma lithium concentration must be monitored. 

Lithium is a drug with a narrow therapeutic index and therefore plasma concentrations are regularly monitored. Lithium is used in the prophylaxis and treatment of mania. Concurrent administration of lithium and diuretics, particularly the thiazides, is contraindicated as lithium excretion is reduced, resulting in increased plasma-lithium concentration and hence toxicity. 

Given the narrow margin between therapeutic and toxic plasma lithium levels, the physician must emphasize the prevention of lithium toxicity through adequate salt and water intake, especially during hot weather and exercise. Toxic lithium levels can cause severe neurotoxic reactions, with symptoms such as dysarthria, ataxia, and in-... 

Another approach has been the study of RBC/plasma lithium concentration, which is an expression of the relationship between intracellular and extracellular levels. 

Lithium + diuretics — reduced lithium clearance and raised plasma lithium concentration thereby enhancing toxicity. 

Lithium is determined in plasma or whole-blood following a twenty-fold dilution with 0.1 N HC1. This would be applicable to monitoring plasma levels in patients receiving lithium carbonate for the treatment of depression. Plasma lithium levels in normal subjects are very low and best determined by electrothermal atomisation. 

Because of the serious risks involved in long-term lithium treatment, patients plasma levels are reassessed regularly, usually every three months. If plasma lithium concentration becomes too high, administration of the drug is suspended and large amounts of sodium salts and fluids are given. Since lithium toxicity is enhanced by sodium depletion, the increased plasma sodium and fluids can reduce its toxic effects. 

Erythrocyte/plasma lithium concentration ratios were lower in patients taking phenothiazines or haloperidol than in those taking lithium alone (620,621), and the former group had a higher incidence of neurological and renal adverse effects (621). 

In 16 subjects, meloxicam 15 mg increased plasma lithium concentrations by 21% (range —9 to 59%) and reduced total plasma lithium clearance by 18% (685). 

In a comparison of lithium concentrations in erythrocytes and plasma during acute or chronic lithium intoxication (309 samples in 165 patients) good general correlation between erythrocyte and plasma lithium concentrations was confirmed (735). There were higher plasma lithium concentrations in acute intoxication and higher erythrocyte lithium concentrations in chronic intoxication the lithium erythrocyterplasma concentration ratio was highest in those with chronic intoxication. 

Levin GM, Gram C, Eisele G. Effect of over-the-counter dosages of naproxen sodium and acetaminophen on plasma lithium concentrations in normal volunteers. J Clin Psychopharmacol 1998 18(3) 237 10. 

LITHIUM SSRIs Lithium may enhance the pharmacologic effects of SSRIs and potentiate the risk of serotonin syndrome. Excessive somnolence has been reported with fluvoxamine. However, there are reports of both T and l plasma concentrations of lithium. There are reports of lithium toxicity and of serotonergic effects Lithium is a direct stimulant of 5-HT receptors, while SSRIs i the reuptake of 5- HT these are considered to t the effects of serotonin in the brain. Seizures are a neurotoxic effect of lithium and could occur even with plasma lithium concentrations within the normal range. SSRIs and lithium may have additive effects to cause seizures Be aware of the possibility of serotonin syndrome. Also need to monitor lithium levels with appropriate dose adjustments during co-administration > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

CANNABIS LITHIUM May t plasma concentrations of lithium Mechanism uncertain Be aware and measure plasma lithium levels if indicated by clinical observations... 

For the expert, cautious addition of a diuretic (e.g., chlorothiazide 50 mg/day) while reducing lithium dose by 50% and monitoring plasma lithium levels may... 

Responses in acute mania may take 7-14 days even with adequate plasma lithium levels... 

Some patients apparently respond to doses as low as 300 mg twice a day, even with plasma lithium levels below 0.5 mEq/L... 

Lower doses and lower plasma lithium levels (<0.6 mEq/L) are often adequate and advisable in the elderiy... 

Non-steroidal anti-inflammatory agents, including ibuprofen and selective Cox-2 inhibitors (cyclo-oxygenase 2), can increase plasma lithium concentrations add with caution to patients stabilized on lithium... 

Neurotoxicity, including delirium and other mental status changes, may occur even at therapeutic doses in elderly and organically compromised patients Lower doses and lower plasma lithium levels (<0.6 mEg/L) are often adequate and advisable in the elderly... 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

Interactions. Hyperkalaemia can result from use with potassium-sparing diuretics. Renal clearance of lithium is reduced and toxic concentrations of plasma lithium may follow. Severe hypotension can occur with diuretics (above), and with chlorpro-mazine, and possibly other phenothiazines. 

Erythrocyte/plasma lithium concentration ratios were lower in patients taking phenothiazines or haloperidol... 

The red blood cell, which is a convenient model, shows a cell-to-plasma lithium ratio of 0.3-0.6, whereas the Nernst equation would predict a 1.6 ratio. When red blood cells are loaded with hthium in vitro its extrusion is accomplished by a Na /LP countertransporter (SLC), the physiological role of which is unclear, but some believe it represents a mode of operation of the Na /H exchanger. Interestingly, a recent paper suggested that red cell SLC may be a marker of the activity of Na /H exchanger-3 the isoform expressed in the kidney proximal tubule rather than the ubiquitous Na /H exchanger-1 isoform [5]. 

In rats with lithium-induced tubulo-interstitial damage, a rise in plasma urea levels after 16 weeks of treatment has been demonstrated even though plasma lithium levels were in the accepted therapeutic range for humans with mood disorders [111]. In contrast to this finding in rats, progression of the chronic tubulointerstitial lesion towards renal insufficiency is unusual in humans. 

Sample material Serum, sodium heparin plasma, lithium heparin plasma or disodium-EDTA plasma. 

Antacid preparations containing sodium bicarbonate should be avoided by patients on lithium therapy. Sodium ions are preferentially reabsorbed in the kidney, increasing lithium excretion and reducing plasma lithium concentrations. 

Lithium carbonate is effective against episodic and chronic cluster headache attacks, with beneficial effects often appearing during the first week of therapy. A positive response is seen in up to 78% of patients with chronic cluster headache and in up to 63% of patients with episodic cluster headache." The usual dose of lithium for cluster headache is 600 to 900 mg/day administered in divided doses. Tachyphylaxis to lithium has been reported occasionally during prolonged therapy." Optimal plasma lithium levels for the prevention of cluster headache have not been established, but efficacy has been reported at relatively low serum concentrations (0.3-0.8 mEq/L)." ... 

Lithium heparinate is the anticoagulant of choice for plasma electrolyte measurements (except, of course, for plasma lithium). Falsely elevated potassium values occur when potassium sequestrenated (EDTA) samples are measured, and the anticoagulant sodium heparinate will give falsely elevated sodium values. Sodium fluoride is a suitable anticoagulant for plasma lactate measurements and is more convenient than iced perchloric acid (Evans 1987). 

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