C H A P T E R 5 1
Diuretic agents
807
T
hiazide and thiazide
-
like diuretics
The thiazide diuretics belong to a chemical class of
drugs called the sulfonamides. Thiazide-like diuretics
have a slightly different chemical structure but work in
the same way as thiazide diuretics.
Thiazide diuretics include hydrochlorothiazide
(
Dithiazide
). Thiazide-like diuretics include chlorthali-
done (
Hygroton
) and indapamide (
Dapa-Tabs
). Thiazide
and thiazide-like diuretics are among the most fre-
quently used diuretics.
Therapeutic actions and indications
Thiazide and thiazide-like diuretics act to block the
chloride pump. Chloride is actively pumped out of the
tubule by cells lining the ascending limb of the loop of
Henle and the distal tubule. Sodium passively moves
with the chloride to maintain electrical neutrality.
(Chloride is a negative ion, and sodium is a positive ion.)
Blocking of the chloride pump keeps the chloride and
the sodium in the tubule to be excreted in the urine,
thus preventing the reabsorption of both chloride and
sodium in the vascular system (see Figure 51.1). Because
Safe medication administration
Explaining fluid rebound
Care must be taken when using diuretics to avoid
fluid
rebound
, which is associated with fluid loss. If a person
stops taking in water and takes the diuretic, the result will
be concentrated plasma of smaller volume. The decreased
volume is sensed by the nephrons, which activate the renin–
angiotensin cycle. When the concentrated blood is sensed by
the osmotic centre in the brain, antidiuretic hormone (ADH)
is released to hold water and dilute the blood. The result can
be a “rebound” oedema as fluid is retained.
Many people who are taking a diuretic markedly decrease
their fluid intake so as to decrease the number of trips to the
bathroom. The result is a rebound of water retention after
the diuretic effect. This effect can also be seen in many diets
that promise “immediate results”; they frequently contain a
key provision to increase fluid intake to 8 to 10 full glasses of
water daily. The reflex result of diluting the system with so
much water is a drop in ADH release and fluid loss.
Some people can lose 2–3 kg in a few days by doing this.
However, the body’s reflexes are quickly activated, causing
rebound retention of fluid to re-establish fluid and electrolyte
balance. People can become frustrated at this point and
give up the fad diet. It is important to be able to explain this
effect. Teaching people about balancing the desired diuretic
effect with the actions of the normal reflexes is a clinical skill.
BOX 51.1
Drug therapy across the lifespan (continued)
People taking potassium-losing diuretics should be
encouraged to eat foods that are high in potassium and to
have their serum potassium levels checked periodically.
People taking potassium-sparing diuretics should be
cautioned to avoid those same foods.
PREGNANCY AND BREASTFEEDING
The use of diuretics to change the fluid shifts associated
with pregnancy is not appropriate. Women maintained
on these drugs for underlying medical reasons should
not stop taking them, but they need to be aware of the
potential for adverse effects on the fetus. Breastfeeding
women who need a diuretic should find another method
of feeding the baby because of the potential for adverse
effects on the baby as well as the breastfeeding mother.
OLDER ADULTS
Older adults often have conditions that are treated with
diuretics.They are also more likely to have renal or hepatic
impairment, which requires cautious use of these drugs.
Older adults should be started on the lowest possible
dose of the drug and the dose should be titrated slowly
based on individual response. Frequent serum electrolyte
measurements should be done to monitor for adverse
reactions.
The intake and activity level of the person can alter the
effectiveness and need for the diuretic. High-salt diets and
inactivity can aggravate conditions that lead to oedema,
and people should be encouraged to follow activity and
dietary guidelines if possible.
Prototype summary: Hydrochlorothiazide
Indications:
Adjunctive therapy for oedema
associated with HF, cirrhosis, corticosteroid or
oestrogen therapy, and renal dysfunction; treatment
of hypertension as monotherapy or in combination
with other antihypertensives.
Actions:
Inhibits reabsorption of sodium and
chloride in distal renal tubules, increasing the
excretion of sodium, chloride and water by the
kidneys.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
2 hours
4–6 hours
6–12 hours
T
1/2
:
5.6–14 hours; metabolised in the liver and
excreted in urine.
Adverse effects:
Dizziness, vertigo, orthostatic
hypotension, nausea, anorexia, vomiting, dry
mouth, diarrhoea, polyuria, nocturia, muscle
cramps or spasms.
