Toxicity lithium

Lithium toxicity can generate side effects even at therapeutic doses. Lithium... 

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. 

Several factors predispose to lithium toxicity, including sodium restriction, dehydration, vomiting, diarrhea, drug interactions that decrease lithium clearance, heavy exercise, sauna baths, hot weather, and fever. Patients should be told to maintain adequate sodium and fluid intake and to avoid excessive coffee, tea, cola, and other caffeine-containing beverages and alcohol. 

If lithium toxicity is suspected, the patient should discontinue lithium and go immediately to the emergency room. Hemodialysis is generally required when serum lithium levels are above 4 mEq/L for patients on long-term treatment, or greater than 6 to 8 mEq/L after acute poisoning. 

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

Groleau G (1994) Lithium toxicity. Emerg Med Clin North Am 12 (2) 511-531 Han L, McCusker J, Cole M et al. (2001) Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med 161 (8) 1099-1105... 

Lithium is an important element in many industries (Bach 1985). Lithium is used medically as a treatment for bipolar disorders (Schou 1988). Lithium toxicity, especially to the renal system, is problematical. Estimating systemic elemental mass balance, especially for patients receiving oral Li dosing, is important, and is one area in which Li isotope ratios are... 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Lithium is somewhat effective for the treatment of agitation however, elderly patients do not tolerate it well. In particular, demented patients are at risk for lithium toxicity, and this toxicity may not be easily detected in these patients. Despite its effectiveness, lithium has been abandoned in the treatment of agitation due to the availability of several effective and better-tolerated treatments, including the atypical antipsychotics described earlier. 

Concurrent administration of lithium and selective serotonin re-uptake inhibitors, such as paroxetine, results in an increased risk of central nervous system effects and lithium toxicity has been reported. 

High-risk patients The risk of lithium toxicity is very high in patients with significant renal or cardiovascular disease, severe debilitation, dehydration, or sodium depletion, or in patients receiving diuretics. Undertake treatment with extreme caution. 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

Lithium is completely absorbed after oral administration reaching peak concentrations after 1-3 hours. Lithium is not metabolized and almost completely excreted unchanged in the urine with a half-life of on average 24 hours, but increasing to 40 hours or longer in the elderly and in patients with compromised renal function. After excretion 70-80% is reabsorbed by proximal renal tubule where it competes with sodium for reabsorption. Therefore low sodium levels decrease lithium excretion with consequent risks for lithium toxicity. 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

Geriatric Considerations - Summary Volume of distribution (Vd), clearance, and half-life are significantly altered in older adults. Lithium toxicity may occur within the usual adult therapeutic range. Older adults are likely to exhibit toxic effects at lower serum concentrations. Significantly lower doses are often efficacious for affective disorders than are used in younger adults. Monitor serum concentrations closely, increased riskof lithium toxicity when a diuretic, NSAID, or ACE Inhibitor is started in a patient already taking lithium. 

Juurlink DN, Mamdani MM, Kopp A, et al. Drug-induced lithium toxicity in the elderly a population-based study 1 Am Geriatr Soc 2004 52 794-798. 

Polyuria, polydipsia, tremor, ataxia, nausea, diarrhea, weight gain, drowsiness, acne, hair loss Possible effects on thyroid and renal functioning with longterm administration Children prone to dehydration are at higher risk for acute lithium toxicity... 

Permanent morphological changes in renal structure have been reported in patients who have experienced lithium toxicity (Markowitz et al. 2000). Case reports of irreversible renal failure as a result of chronic, nontoxic lithium therapy are extremely rare and typically foUow 10 or more years of treatment, during which time the patient s serum creatinine levels have gradually increased (e.g., to 2.0 mg/100 mL Gitlin 1993). To minimize the risk of renal complications, which are rare but potentially serious, we recommend frequent patient education about the risks of toxicity and factors that might make toxicity more likely, such as drug interactions or dehy-... 

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-... 

In a patient with a serum lithium level greater than 4.0 mEq/L or with serious manifestations of lithium toxicity, hemodialysis should be initiated. ... 

Repeat dialysis may be required every 6-10 hours, until the lithium level is within nontoxic range and the patient has no signs or symptoms of lithium toxicity. 

Mehta BR, Robinson BHB. Lithium toxicity induced by triamterene-hydrochlorothiazide. Postgrad Med J 1980 56 783-784. 

Salama AA, Shafey M. A case of severe lithium toxicity induced by combined fluoxetine and lithium carbonate [Letter]. Am J Psychiatry 1989 146 278. 

Lithium toxicity (chronic, subacute, or acute) can be secondary to any factor that reduces body clearance, or secondary to acute or sustained elevated doses (and therefore plasma levels) (342). The degree of toxicity can be classified as follows ... 

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