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P A R T 9
Drugs acting on the renal system
sodium is reabsorbed. This action decreases the reab-
sorption of sodium and chloride. The loop diuretics
have a similar effect in the descending loop of Henle and
in the distal convoluted tubule, resulting in the produc-
tion of a copious amount of sodium-rich urine. These
drugs work even in the presence of acid–base distur-
bances, renal failure, electrolyte imbalances or nitrogen
retention.
Because they can produce a loss of fluid of up to
10 L/day, loop diuretics are the drugs of choice when a
rapid and extensive diuresis is needed. In cases of severe
oedema or acute pulmonary oedema, it is important to
remember that these drugs can have an effect only on
the blood that reaches the nephrons. A rapid diuresis
occurs, producing a more hypertonic intravascular fluid.
In pulmonary oedema, this fluid then circulates back to
the lungs, pulls fluid out of the interstitial spaces by its
oncotic pull, and delivers this fluid to the kidneys, where
the water is filtered out, completing the cycle. In the
treatment of pulmonary oedema, it can sometimes take
hours to move all of the fluid out of the lungs because
the fluid must be removed from the interstitial spaces
in the lungs before it can be circulated to the kidneys
for removal. Remembering how the drugs work and the
way in which fluid moves in the vascular system will
make it easier to understand the effects to anticipate.
Loop diuretics are commonly indicated for the treat-
ment of acute HF, acute pulmonary oedema, oedema
associated with HF or with renal or liver disease and
hypertension. See Table 51.1 for usual indications for
each of these agents. Frusemide is less powerful than
bumetanide and therefore has a larger margin of safety
for home use.
See the Critical thinking scenario for
additional information about using frusemide in HF
.
Ethacrynic acid is used less frequently in the clinical
setting because of the improved potency and reliability
of the other drugs.
Pharmacokinetics
Loop diuretics are available for oral or IV use. Fruse-
mide may also be given IM. They reach peak levels in
60 to 120 minutes (orally) or 30 minutes (parenterally)
and are metabolised with a half-life of 30 to 60 minutes
and excreted primarily through urine.
Contraindications and cautions
Among the contraindications to these drugs are allergy
to a loop diuretic
to prevent hypersensitivity reactions
;
electrolyte depletion,
which could be aggravated by the
electrolyte effects of these drugs
; anuria—severe renal
failure,
which may prevent the diuretic from working or
precipitate a crisis stage due to the blood flow changes
brought about by the diuretic
; and hepatic coma,
which
could be exacerbated by the fluid shifts associated
with drug use.
Routine use during pregnancy is not
appropriate;
these drugs should be reserved for situa-
tions in which the mother has pathological reasons for
use, not pregnancy manifestations or complications, and
only if the benefit to the mother clearly outweighs the
risk to the fetus.
Caution should be used with the following condi-
tions: SLE,
which frequently causes glomerular changes
and renal dysfunction that could precipitate renal
failure in some cases
; glucose tolerance abnormalities or
diabetes mellitus,
which are worsened by the glucose-
elevating effects of many diuretics
; and gout,
which
reflects an abnormality in normal tubule reabsorption
and secretion
.
Safety for use in children younger than 18 years of
age has not been established. If one of these drugs is used
for a child, careful monitoring of the child’s fluid and
electrolyte balance is needed, and emergency support
measures should be on standby.
Adverse effects
Adverse effects are related to the imbalance in electro-
lytes and fluid that these drugs cause. Hypokalaemia
is a very common adverse effect because potassium is
lost when the transport systems in the tubule try to save
some of the sodium being lost.
Alkalosis
, or a drop in
serum pH to an alkaline state, may occur as bicarbonate
is lost in the urine. Calcium is also lost in the tubules
along with the bicarbonate, which may result in hypo
calcaemia and tetany. The rapid loss of fluid can result
in hypotension and dizziness if it causes a rapid imbal-
ance in fluid levels. Long-term use of these drugs may
also result in hyperglycaemia because of the diuretic
effect on blood glucose levels, so susceptible individu-
als need to be monitored for this effect. Ototoxicity and
even deafness have been reported with these drugs, but
Prototype summary: Frusemide
Indications:
Treatment of oedema associated with
HF, acute pulmonary oedema, hypertension.
Actions:
Inhibits the reabsorption of sodium and
chloride from the distal renal tubules and the loop
of Henle, leading to a sodium-rich diuresis.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
60 mins
60–120 mins 6–8 hours
IV, IM 5 mins
30 mins
2 hours
T
1/2
:
120 minutes; metabolised in the liver and
excreted in urine.
Adverse effects:
Dizziness, vertigo, paraesthesias,
orthostatic hypotension, rash, urticaria, nausea,
anorexia, vomiting, glycosuria, urinary bladder
spasm.
