Lithium with thiazide diuretics

Unlabeled uses Amiloride (10 to 20 mg/day) may be useful in reducing lithium-induced polyuria without increasing lithium levels as is seen with thiazide 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. 

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. 

If serum Na+ is not monitored closely, ADH antagonists can cause severe hypernatremia and nephrogenic diabetes insipidus. If lithium is being used for a psychiatric disorder, nephrogenic diabetes insipidus can be treated with a thiazide diuretic or amiloride. 

In an 80-year-old woman a 2-month history of diarrhea, nausea, and abdominal distress attributed to irritable bowel syndrome was ultimately determined to be due to early lithium intoxication (356). Her lithium concentration when she was hospitalized was 1.2 mmol/1, although she had taken no lithium for the previous 10 days. Treatment with a thiazide diuretic contributed to the toxicity. 

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... 

In cases where sufficient tubulointerstitial damage causing impaired concentrating ability has occurred, amiloride is less effective still, it can be used in combination with a thiazide diuretic to reduce polyuria [2]. Moreover, hypokalemia, a common side effect of thiazides, is not observed with amiloride [26]. Amiloride obviates the need for potassium supplementation, which is required when thiazide diuretics are used to treat polyuria and, in addition, is less likely to cause lithium intoxication. Although both lithium and amiloride interfere with distal urinary acidification. 

Usually neither hyperkalemia nor hypokalemia pose a problem for the management of lithium treated patients. However, in lithium-treated subjects given thiazide diuretic, hypokalemia often develops [97]. This is due to the diuretic-induced increase in sodium delivery to the collecting tubule combined with the lithium-induced increase in urine flow. 

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... 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, anticholinergics, antihistamines, barbituates, cisapride, dofetilide, doxazosin, erythromycin, guanethidine, hydralazine, levodopa, lithium, methyldopa, metoclopramide, moxifloxacin, piperazine, quinidine, sibutramine, sotalol, thiazide diuretics, thioridazine... 

Not fully understood. If and when a rise in serum-lithium levels occurs, it may be related to the salt depletion that can accompany the use of furo-semide (for a more detailed explanation see Lithium + Sodium compounds , p.l 128). As with the thiazide diuretics, (p.l 123) such an interaction would take a few days to develop. This may explain why one study in subjects given a single dose of lithium failed to demonstrate that furosemide had any effect on the urinary excretion of lithium. ... 

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. 

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. 

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. 

The use of diuretics, such as a thiazide or amiloride, with careful attention paid to lithium and potassium levels ( 318, 319)... 

Renal clearance of lithium is reduced about 25% by diuretics (eg, thiazides), and doses may need to be reduced by a similar amount. A similar reduction in lithium clearance has been noted with several of the newer nonsteroidal anti-inflammatory drugs that block synthesis of prostaglandins. This interaction has not been reported for either aspirin or acetaminophen. All neuroleptics tested to date, with the possible exception of clozapine and the newer atypical antipsychotics, may produce more severe extrapyramidal syndromes when combined with 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. 

Diuretics, especially thiazides, can increase plasma lithium concentrations add with caution to patients stabilized on lithium... 

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