Lithium with loop diuretics

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

LOOP DIURETICS ANTIDEPRESSANTS-LITHIUM t plasma concentrations of lithium, with risk of toxic effects L renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides... 

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. 

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. 

Both drugs are used in conjunction with other diuretics like thiazide or loop diuretics to augment natriuresis and reduce loss of potassium. Triamterene may be used in the treatment of congestive heart failure, cirrhosis and the edema caused by secondary hyperaldosteronism. Amiloride is also useful in lithium induced diabetes insipidus. 

Analgesics, such as aspirin or acetaminophen, and furosemide, a loop diuretic, are better choices because they apparently do not interfere with lithium s reabsorption. 

The risk of hospital admission related to lithium toxicity has been estimated in a case-control study of 10 615 elderly patients over 9 years (512). Lithium toxicity occurred at least once in 413 of the patients who were taking lithium. Factors that increase the likelihood of hospital admission included starting treatment with a loop diuretic or ACE inhibitors during the month before hospitalization. Although furosemide has been suggested as the diuretic of choice for patients taking lithium, the authors suggested that furosemide may cause lithium... 

Although amiloride may reduce the renal clearance of lithium, it appears to be free of the troublesome interaction with lithium that complicates the use of thiazides and loop diuretics. 

The loop diuretics increase the renal excretion of lithium after single-dose intravenous administration in both animals (711) and man (712). Furosemide has been used to treat lithium intoxication (713). The effect of etacrynic acid is larger than those of furosemide and bumetanide (712). However, long-term treatment with furosemide and bumetanide can cause lithium intoxication in some patients (714,715), perhaps by causing sodium depletion and a secondary increase in lithium reabsorption. An adverse interaction of lithium during long-term therapy with etacrynic acid is therefore theoretically likely. 

Huang LG. Lithium intoxication with coadministration of a loop-diuretic J Chn Psychopharmacol 1990 10(3) 228. 

Loop diuretics (especially as i.v. boluses) potentiate ototoxicity of aminoglycosides and nephrotoxicity of some cephalosporins. NSAIDs tend to cause sodium retention which counteracts the effect of diuretics the mechanism may involve inhibition of renal prostaglandin formation. Diuretic treatment of a patient taking lithium can precipitate toxicity from this drug (the increased sodium loss is accompanied by reduced lithium excretion). Reference is made above to drug treatments which, when combined with diuretics, may lead to hyper-kalaemia, hypokalaemia, hyponatraemia, or glucose intolerance. 

Edema associated with lithium is uncommon (249,250). It is usually restricted to the legs, and is usually transient or intermittent. If treatment is necessary, the intermittent and cautious use of a loop diuretic may be helpful (but see drug-drug interactions). 

Acetazolamide, and probably other diuretics which inhibit carbonic anhydrase, cause a strong inhibition of proximal NaHCOg reabsorption and lithium reabsorption. However, unlike loop diuretics, acetazolamide does not interfere with tubuloglomerular feedback and causes a 20% decrease in glomerular filtration rate. The increase in absolute lithium excretion is somewhat lower than that caused by loop diuretics [22]. Colussi et al. [25] reported the effect of furosemide and acefazola-mide to be additive, indicating a dual site of action (i.e., inhibition of lithium reabsorption in both the proximal tubule and the loop of Henle). 

Volume resuscitation is the cornerstone of management of lithium toxicity (Table 3) [124, 125]. Patients with underlying lithium-induced diabetes insipidus may initially present with volume depletion. It must be borne in mind, however, that hypernatremia [125] is a potential complication, especially in those with underlying diabetes insipidus. Forced saline diuresis is expected to increase lithium clearance by decreasing proximal tubular reabsorption. With normal renal function, lithium can be cleared at a rate of 10-40 mL/min [125]. The excretion of lithium can be further increased acutely by using acetazolamide and/or loop diuretics [124,125]. 

Michimata M, Fujita S, ArakiT, Mizukami K, Kazama I, Muramatsu Y, Suzuki M, kImuraT, Sasaki Ss, Imal Y, Matsubara M. Reverse pharmacological effect of loop diuretics and altered rBSCl expression In rats with lithium nephropathy. Kidney Int 2003 63(1 ) 165-171. 

Lithium is also known to interact in a variety of ways with different classes of diuretic drugs. Thiazide diuretics increase serum lithium concentration by increasing reabsorption of lithium, along with that of sodium, in the proximal tubule. With potassium-sparing diuretics, conflicting results have been reported. Increased serum lithium concentrations may be seen after amiloride. However, the loop diuretic furosemide safely can be combined with lithium with no reduction in renal lithium clearance or consequent increase in serum lithium concentration (191, 192). Other diuretics, for example, carbonic anhydrase inhibitor and xanthine derivatives, decrease serum... 

The concurrent use of lithium carbonate and furosemide can be safe and uneventful, but serious lithium toxicity has been described. Bumetanide interacts similarly. The risk of lithium toxicity with a loop diuretic is greatly increased during the first month of concurrent use. 

A 75-year-old man developed severe lithium toxicity, with a Glasgow Coma Scale score of 7, 1 month after adding a loop diuretic and an ACE inhibitor to lithium [61 ]. 

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. 

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