Renal impairment lithium

The NSAIDs prolong bleeding time and increase the effects of anticoagulants, lithium, cyclosporine, and the hydantoins. These dru may decrease the effects of diuretics or antihypertensive drug >. Long-term use of the NSAIDs with acetaminophen may increase the risk of renal impairment. 

Q70 Lith ium should be stopped 24 hours before major surgery. Lithium should be avoided if possible in renal impairment. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

There is no final consensus on whether normal use of lithium, without any episode of toxicity (the vast majority of patients), may result in permanent renal impairment. Polyuria occurs in 20-40% and is due to inhibition of antidiuretic hormone (ADH) by lithium. It usually resolves on cessation of lithium as do any effects on glomerular function. Interference with thyroid function is due to inhibition of the action of thyroid stimulating hormone (TSH) and is easily managed by administration of thyroxine. Lithium is contraindicated during pregnancy (major vessel anomalies in fetus) and breastfeeding. 

A 56-year-old man with normal renal function and therapeutic lithium concentrations became toxic (serum concentration 2.53 mmol/1 24 hours after the last dose) with renal impairment (serum creatinine 141 gmol/l 1.6 mg/ dl) within days of starting levofloxacin. Both symptoms and laboratory abnormalities resolved with withdrawal of both lithium and levofloxacin (615). 

Toxic effects of lithium can be fatal. Early signs of lithium toxicity are vomiting and severe diarrhoea followed by tremor, ataxia, renal impairment and convulsions. Many non-steroidal anti-inflammatory drugs interact with lithium to increase its plasma... 

A woman taking lithium carbonate developed signs of lithium toxicity (ataxia, dysarthria, tremor, confusion) within 2 to 3 weeks of starting to take enalapril 20 mg daily. After 5 weeks her plasma-lithium levels had risen from 0.88 to 3.3 mmol/L, and moderate renal impairment was noted. No toxicity occurred when the enalapril was later replaced by nifedipine. Lithium toxicity following the use of enalapril, and associated in some cases with a decrease in renal function, has been seen in another 5 patients, " and a reduced lithium dosage was found adequate in another patient. Enalapril 5 mg daily for 9 days had no effect on the mean serum-lithium levels of 9 healthy male subjects. However, one subject had a 31% increase in lithium levels. "... 

Although the combined use of lithium and carbamazepine is beneficial in many patients, it may increase the risk of neurotoxicity. Sinus node dysfunction has also occurred in a few patients. An isolated report describes a patient who had a marked rise in lithium levels and lithium toxicity, which was apparently caused by carbamazepine-induced renal impairment. 

Isolated case reports describe either a fall or no alteration in serum-lithium levels in patients given cisplatin. However, note that cisplatin-induced renal impairment may cause an increase in lithium levels. 

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. ... 

One UK manufacturer warns that drugs affecting electrolyte balance, such as corticosteroids, may alter lithium excretion and should therefore be avoided, but other manufaeturers do not appear to mention this potential interaction. An early study in rats reported increased lithium clearance with methylprednisolone. The available evidence is insufficient to recommend routine monitoring. However, it may be prudent to consider monitoring lithium effects in patients with renal impairment, or other conditions pre-disposing to lithium toxicity, taking levels if early symptoms suggest a potential problem. 

A 58-year-old woman, with a stable serum-lithium level of between 0.5 and 0.9 mmol/L, developed renal impairment associated with severe lithium toxicity, within 5 days of starting to take celecoxib 400 mg twice daily. Her lithium level was 4 mmol/L. Of note, and a possible contributory factor, was the presence of ibuprofen, which she had taken with her lithium for several years without incident. ... 

A case report describes lithium toxicity in a man given indometacin 50 mg every 6 hours. Three days after he started the indometacin his serum creatinine was raised, and 9 days later he had symptoms of lithium toxicity and was found to have a lithium levels of 3.5 mmol/L. It was suggested that the indometacin caused renal impairment, which led to lithium retention and toxicity. ... 

Renal function impairment Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have occurred in patients on chronic lithium therapy. The relationship between such changes and renal function has not been established. 

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. 

A related issue is the patient s ability to metabolize and eliminate drugs adequately. For example, lithium is excreted entirely by the kidneys, and if a patient suffers from significantly impaired renal function, high, potentially toxic levels could develop on standard doses. Although the dose could be adjusted to compensate for the decrease in drug clearance, it might be more appropriate to choose another mood stabilizer such as valproate or carbamazepine, because they are primarily metabolized through the liver. 

The management of toxicity requires monitoring of electrolytes, regular CNS observations, use of anticonvulsants should seizures occur, increased fluid intake to promote excretion (unless renal function is impaired) and cardiac monitoring. Haemodialysis should be considered if conservative measures are ineffective or serum lithium is above 3.0 mmol L-l. However, it may be of limited additional value as the volume of distribution of lithium is high. 

Prostaglandin inhibition may result in reduced renal sodium excretion, impaired resistance to hypertensive stimuli, and reduced renal lithium excretion. Most NSAIDs inhibit platelet function may increase likelihood of bleeding due to other drugs that impair hemostasis. Most NSAIDs are highly bound to plasma proteins. 

To what extent long-term treatment with lithium impairs GFR is a matter of continued study (360). Lithium does not appear to impair GFR consistently, especially if correction is made for age-related changes in kidney function, although in one study there was an age-related reduction in 21% of 142 patients who had taken lithium for at least 15 years (366). There have been a few case reports of progressive renal insufficiency attributed to lithium, but it has not been possible to establish a cause-and-effect relation with absolute certainty. 

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