Effects of Long-Term Administration of Lithium and Hydrochlorothiazide in Rats

Felicia Loghin,Sorin E Leucuta,Carmen Socaciu,Daniela-Saveta Popa,Adriana Olinic

doi:10.1155/mbd.1999.87

Abstract

The biochemical and histological changes following 60 days administration of daily doses equivalent to 1/20 LD50 of lithium lactate and hydrochlorothiazide, as such and in association, were studied in male Wistar rats. No mortality or overt signs of toxicity were observed during the experiment and the serum activities of transaminases, alkaline phosphatase and cholinesterase were not significantly modified compared to controls. The histopathological examination of all the investigated organs: kidney, liver, brain and spleen, revealed significant lesions which were time-dependant and more pronounced in the association group. Although the changes were mostly inflammatory and conqestive, it was proved that the concomitant administration of lithium and hydrochlorothiazid is potentially dangerous, increasing lithium’s nephrotoxicity and the thiazide diuretic's hepatotoxicity.

Highlights

Lithium is a major drug in psychiatry, being used in the treatment and prophylaxis of bipolar affective disorder, and in antidepressant-resistant patients (1,2,3)
Lithium’s pharmacokinetics is relatively simple, but the ion can pharmacokinetically interact with many usual drugs which may be prescribed for the treatment of an illness accompanying the psychiatric disorder: diuretics, nonsteroidal anti-inflammatory drugs, antibiotics, bronchodilators (4,5,6,7)
In order to evaluate this risk, we have studied in male Wistar rats the biochemical and histological changes during long-term administration of lithium and hydrochlorothiazide as such and associated

Summary

Introduction

Lithium is a major drug in psychiatry, being used in the treatment and prophylaxis of bipolar affective disorder, and in antidepressant-resistant patients (1,2,3). Lithium’s pharmacokinetics is relatively simple, but the ion can pharmacokinetically interact with many usual drugs which may be prescribed for the treatment of an illness accompanying the psychiatric disorder: diuretics, nonsteroidal anti-inflammatory drugs, antibiotics, bronchodilators (4,5,6,7). The thiazide diuretics have been recommended by some authors for the treatment of lithium-induced nephrogenic diabetes insipidus and in severe manic-depressive illness in which high doses of lithium do not produce therapeutic serum concentrations (8). Thiazide diuretics inhibit sodium reabsorption in the distal tubule, inducing sodium depletion. During long-term administration, the diuretic-induced sodium depletion results in a compensatory increased reabsorption of both sodium and lithium in the proximal tubule. 80% of lithium that has been glomerulary filtered is usually reabsorbed, but sodium depletion induces about 86% reabsorption (9). Lithium concentrations can be significantly increased by diuretic therapy, with risk of intoxication

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Discussion

Conclusion