Polyuria lithium treatment

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via anti diuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

Polydipsia and polyuria are common but reversible concomitants of lithium treatment, occurring at therapeutic serum concentrations. The principal physiologic lesion involved is loss of responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus). Lithium-induced diabetes insipidus is resistant to vasopressin but responds to amiloride. 

The polyuria which often accompanies lithium treatment is normally compensated for by drinking water, but when consciousness is impaired severe hypernatremia may develop. When any acute illness (particularly if associated with gastrointestinal symptoms) occurs or when new medication is given, lithium blood levels should be closely monitored, and the lithium dose adjusted. 

Unlabeled Uses Treatment of edema associated with CHF, liver cirrhosis, and nephrotic syndrome treatment of hypertension reduces lithium-induced polyuria, slows pulmonary function reduction in cystic fibrosis... 

Rosten MD, Forest JN. Treatment of severe lithium-induced polyuria with amiloride. Am J Psychiatry 1986 143 1563-1568. 

When 60 patients (22 men, 38 women) who had taken lithium for 1 year or more (mean 6.9 years mean serum concentration 0.74 mmol/1) were interviewed about adverse effects, 60% complained of polyuria-polydipsia syndrome (serum creatinine concentrations were normal) and 27% had hypothyroidism requiring treatment (108). Weight gain was more common in women (47 versus 18%) as were hypothyroidism (37 versus 9%) and skin problems (16 versus 9%), while tremor was more common in men (54 versus 26%). Weight gain of over 5 kg in the first year of treatment was the only independent variable predictive of hypothyroidism. 

Long-term use of lithium is sometimes associated with weight gain, polyuria and polydipsia, and thyroid dysfunction (see below), but many patients have been treated successfully for several decades without developing treatment-limiting adverse effects. However, long-term success should not breed complacency, since there is an ever-present risk of recurrence (if concentrations are too low) and toxicity (if concentrations are too high). 

Treatment of lithium-induced polyuria Other complications of lithium administration. Drug interactions ... 

We utihzed the above principle to treat hthium-induced polyuria [26]. This reduction in urine output could not be ascribed to increased proximal fluid reabsorption and decreased dehvery of fluid to the distal nephron as a result of the volume contraction caused by amiloride. Fractional lithium excretion, a marker of proximal sodium reabsorption, did not fall during amiloride treatment, arguing against volume contraction induced by amiloride as possible mechanism [26]. In lithium treated patients, urinary osmolality increased when treated with amiloride. Amiloride attenuates the inhibitory effect of lithium on vasopressin-mediated water reabsorption [26] (Figure 3). 

Treatment of lithium-induced polyuria Effect of lithium on distal nephron acidification Potassium balance... 

A number of drugs inhibit the antidiuretic actions of vasopressin. Lithium is of particular importance because of its use in the treatment of manic-depressive disorders. Lithium-induced polyuria is usually reversible. Acutely, lithium appears to reduce V -receptor-mediated stimulation of adeny-lyl cyclase. Also, hthium increases plasma levels of parathyroid hormone, a partial antagonist to vasopressin. In most patients, the antibiotic demeclocycline attenuates the antidiuretic effects of vasopressin, probably owing to decreased accumulation and action of cyclic AMP. 

Amiloride has been found to have no signifieant effeet on serum-lithium levels when used in the treatment of lithium-indueed polyuria. One review briefly mentions a ease report in whieh amiloride was sueeessfully used as a replaeement for bendroflumethiazide, whieh had eaused lithium toxieity 2 However, some manufaeturers" suggest that, as a diuretie, amiloride reduees the renal elearanee of lithium, thereby inereasing the risk of lithium toxieity. There appears to be no evidenee to eonfirm this alleged interaetion. 

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