808
P A R T 9
Drugs acting on the renal system
these segments of the tubule are impermeable to water,
there is little increase in the volume of urine produced,
but it will be sodium rich, a
saluretic effect
. Thiazides
are considered to be mild diuretics compared with the
more potent loop diuretics. These drugs are the first-line
drugs used to manage essential hypertension when drug
therapy is needed. See Table 51.2 for usual indications
for these agents.
Pharmacokinetics
These drugs are well absorbed from the GI tract after
oral administration, with onset of action ranging
from 1 to 3 hours. They have peak effects within 4 to
6 hours and duration of effects of 6 to 12 hours. They
are metabolised in the liver and excreted in the urine.
These diuretics cross the placenta and enter breast milk.
Hydrochlorothiazide is the most frequently used of the
thiazide diuretics and the prototype of this class.
Contraindications and cautions
Thiazide and thiazide-like diuretics are contraindi-
cated with allergy to thiazides or sulfonamides
to
prevent hypersensitivity reactions
; fluid and electrolyte
imbalances,
which can be potentiated by the fluid and
electrolyte changes caused by these diuretics
; and severe
renal disease,
which may prevent the diuretic from
working or precipitate a crisis stage due to the blood
flow changes brought about by the diuretic.
Caution should be used with the following con-
ditions: systemic lupus erythematosus (SLE),
which
frequently causes glomerular changes and renal dysfunc-
tion that could precipitate renal failure in some cases
;
glucose tolerance abnormalities or diabetes mellitus,
which is worsened by the glucose elevating effects of
many diuretics
; gout,
which reflects an abnormality in
normal tubule reabsorption and secretion
; liver disease,
which could interfere with the normal metabolism of
the drugs, leading to an accumulation of the drug or
toxicity
; hyperparathyroidism,
which could be exacer-
bated by the renal effects of these drugs
; and bipolar
disorder,
which could be exacerbated by the changes
in calcium levels that occur with these drugs
. Routine
use during pregnancy is not appropriate; these drugs
should be reserved for situations in which the mother
has pathological reasons for use, not pregnancy mani
festations or complications, and only if the benefit to
the mother clearly outweighs the risk to the fetus. If one
of these drugs is needed during breastfeeding, another
method of feeding the baby should be used
because of
Proximal
convoluted
tubule
Distal
convoluted
tubule
Collecting
duct
Ascending
loop of Henle
Descending
loop of Henle
Osmotic
diuretics
Spironolactone
Carbonic
anhydrase
inhibitors
Loop
diuretics
Thiazides,
thiazide-like
diuretics
FIGURE 51.1
Sites of action of diuretics in the nephron.
