THIAZIDE DIURETICS

A. Prototypes and Mechanism of Action

Hydrochlorothiaide! the prototypical agent, and all the other
members of this group are sulfonamide derivatives. A few derivatives
that lack the typical thiazide ring in their structure nevertheless
have effects identical with those of thiazides and are therefore
considered thiazide-like. The major action of thiazides is to inhibit
sodium chloride transport in the early segment of the distal convoluted
tubule (!!, "igure #$%&'. Thiazides are active by the
oral route and have a duration of action of (%#) h, considerably
longer than most loop diuretics.
". Effects
*n full doses, thiazides produce moderate but sustained sodium
and chloride diuresis. +ypokalemic metabolic alkalosis may
occur (Table #$%#'. ,eduction in the transport of sodium from
the lumen into the tubular cell reduces intracellular sodium and
promotes sodium-calcium e-change at the basolateral membrane
As a result, reabsorption of calcium from the urine is increased,
and urine calcium content is decreased.the opposite of the effect
of loop diuretics. /ecause they act in a diluting segment of the
nephron, thiazides may reduce the e-cretion of water and cause
dilutional hyponatremia. Thiazides also reduce blood pressure,
and the ma-imal pressure-lowering effect occurs at doses lower
than the ma-imal diuretic doses (see !hapter ##'. *nhibition of
renal prostaglandin synthesis reduces the efficacy of the thiazides.
0hen a thiazide is used with a loop diuretic, a synergistic effect
occurs with marked diuresis.
C. Clinical Use and To#icities
The major application of thiazides is in hypertension, for which
their long duration and moderate intensity of action are particularly
useful. !hronic therapy of edematous conditions such as
mild heart failure is another application, although loop diuretics
are usually preferred. !hronic renal calcium stone formation can
sometimes be controlled with thiazides because they reduce urine
calcium concentration.
1assive sodium diuresis with hyponatremia is an uncommon
but dangerous early to-icity of thiazides. !hronic therapy is often
associated with potassium wasting, since an increased sodium
load is presented to the collecting tubules2 the cortical collecting
tubules compensate by reabsorbing sodium and e-creting
potassium. 3iabetic patients may have significant hyperglycemia.
4erum uric acid and lipid levels are also increased in some
persons. Thiazides are sulfonamides and share potential sulfonamide
allergenicity.