TIp 22 (February 2014)
Thiazide-induced hyponatraemia
Thiazide diuretics revolutionised the management of hypertension when they were first introduced in
about 1957. They were the first antihypertensive class which combined efficacy and tolerability. And they
were subsequently shown to reduce cardiovascular morbidity and mortality in many large outcome trials.
They remain an important (and sometimes indispensible) part of the antihypertensive drug armamentarium.
Even in 2014 they are the third most commonly used antihypertensive drug class in patients coming
through the Waitemata Hypertension Clinic, and my private practice - after ACE-inhibitors (or ARB’s) and
DHP calcium channel blockers.
Most doctors are aware of the potential metabolic side-effects of thiazides including hypokalaemia,
hyponatraemia, hyperuricaemia, and impaired glucose tolerance. Hypokalaemia is the commonest. It is
generally not an indication for drug withdrawl, and is usually manageable with potassium supplementation
or by combining the thiazide with a potassium sparing drug. The most serious (an even potentially lifethreatening) side-effect is hyponatraemia, and unlike hypokalaemia, unless very mild, is usually an
indication for drug withdrawl. One of our house-officers, Dr Sergej Cicovic, did and audit of our
experience of thiazide-hyponatraemia which has been published in this month’s issue of an on-line
hypertension journal1.
What he showed was that at least 10% of patients coming through our clinic were thiazide intolerant
specifically due to hyponatraemia. And importantly (as has been reported elsewhere) risk factors are female
sex, older age, low BMI, and coexisting treatment with ACE-inhibitors or ARB’s. In other words, the
typical patient who develops hyponatraemia is a female, over 70, with low body weight. This does not
mean that thiazides should be avoided in this group, but make sure you start at low doses (eg
bendrofluazide 12.5mg daily, hydrochlorothiazide 12.5mg daily, indapamide 1.25mg daily), and check
electrolytes 1-2 week after commencement and any subsequent dose adjustment.
You may know from these pages that chlorthalidone is my favourite thiazide (-like) diuretic, but even the
smallest available dose is 12.5mg (1/2 of a 25mg tablet) is quite potent, and I would not start it (first-off
anyway) in a slim older woman. By contrast, I know that a robust, 90kg, 50 year old male is extremely
unlikely to develop hyponatraemia, and in that group I am happy to start with chlorthalidone 12.5 or even
25mg daily.
1 Thiazide Intolerance, a New Zealand Perspective. Cicovic S et al. J Hypertens. 2014;3:1
(this is a free on-line journal- “Google J Hypertens –Open Access” – click on “readers”, then”current
issue)
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