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Letter: Diuretics during lithium therapy.

S MacNeil·E Hanson-Nortey·C Paschalis·P R Eastwood·F A Jenner
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DiuresisDiureticsDrug InteractionsHumansLithiumPolyuriaThiazinesJournal Article

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S MacNeil, E Hanson-Nortey, C Paschalis, P R Eastwood, F A Jenner. 1975-06-07. Letter: Diuretics during lithium therapy.. https://doi.org/10.1016/s0140-6736(75)92579-9

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The clinical use of measurements of drug concentrations in blood is empirical and largely confined to compliance and toxicity monitoring. As currently used in once or thrice a day dosage, lithium treatment is pulsatile, the blood concentration varying threefold over 24 hours; routine measurements reveal nothing of this and therefore do not aid therapeutic use. In a pilot study it is shown that the plasma lithium concentration can be raised from 0 to 2 mmol/l in a few hours, inducing changes in both kidney function and neuropsychological tests after only short delay. This suggests that mania might be quickly controlled with rapid dosage and opens up a new way of analysing the mechanisms of lithium action, or of using it to reveal changes in cerebral functioning.

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Xipamide, hydrochlorothiazide, and furosemide were given to normal volunteers on a double-blind basis. During maximal water diuresis, there was a reduction in free water clearance and an increase in osmolar clearance after administration of xipamide and hydrochlorothiazide, but not in the case of furosemide. During maximal hydropenia, both xipamide and hydrochlorothiazide increased free water reabosorption in a linear relationship to osmolar clearance, while furosemide increased osmolar clearance with little change in free water reabsorption. It was concluded, therefore, that, as with hydrochlorothiazide, the site of action of xipamide was on the distal convoluted tubule, and that of furosemide on the loop of Henle.

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