C H A P T E R 5 1
Diuretic agents
809
the potential for adverse effects on fluid and electrolyte
changes in the baby
.
Adverse effects
The most common adverse effects associated with
diuretic agents include GI upset, fluid and electrolyte
imbalances, hypotension and electrolyte disturbances.
Adverse effects associated with the use of thiazide and
thiazide-like diuretics are related to interference with the
normal regulatory mechanisms of the nephron. Potas-
sium is lost at the distal tubule because of the actions on
the pumping mechanism, and
hypokalaemia
(low blood
levels of potassium) may result. Signs and symptoms of
hypokalaemia include weakness, muscle cramps and
arrhythmias. Another adverse effect is decreased calcium
excretion, which leads to increased calcium levels in the
blood. Uric acid excretion is also decreased because the
thiazides interfere with its secretory mechanism. High
levels of uric acid can result in gout.
If these drugs are used over a prolonged period,
blood glucose levels may increase. This may result from
the change in potassium levels (which keeps glucose out
of the cells), or it may relate to some other mechanism of
glucose control.
Urine is slightly alkalinised when the thiazides
or thiazide-like diuretics are used because they block
the reabsorption of bicarbonate. This effect can cause
problems for individuals who are susceptible to bladder
infections.
Clinically important drug–drug interactions
Decreased absorption of these drugs may occur if they
are combined with cholestyramine or colestipol. If this
combination is used, the drugs should be taken sepa-
rated by at least 2 hours.
The risk of digoxin toxicity increases due to potential
changes in potassium levels; serum potassium should be
monitored if this combination is used. Risk of quinidine
toxicity increases due to decreased quinidine excretion
with an alkaline urine, leading to increased serum levels
of quinidine. If this combination is used, the person
must be monitored closely and quinidine dose decreased
as appropriate.
Decreased effectiveness of agents to control elevated
blood glucose levels may occur related to the changes
in glucose metabolism; dose adjustment of those agents
may be needed.
The risk of lithium toxicity may increase if these
drugs are combined. Serum lithium levels should be
monitored and appropriate dose adjustment made as
needed.
L
oop diuretics
Loop diuretics are so named because they work in
the loop of Henle. Loop diuretics are also referred to
as
high-ceiling diuretics
because they cause a greater
degree of diuresis than other diuretics do. Three loop
diuretics are available: ethacrynic acid (
Edecrin
[not
available in New Zealand]) the first loop diuretic intro-
duced; bumetanide (
Burinex
); and frusemide (
Lasix
),
the most commonly used loop diuretic.
Therapeutic actions and indications
Loop diuretics block the chloride pump in the ascend-
ing loop of Henle, where normally 30% of all filtered
■■
TABLE 51.2 Comparison of diuretics
Diuretic class
Major site of action Usual indications
Major adverse effects
Thiazide,
thiazide-like
Distal
convoluted
tubule
Oedema of HF, liver and renal disease
Adjunct for hypertension
GI upset, CNS complications,
hypovolaemia
Loop
Loop of Henle
Acute HF
Acute pulmonary oedema
Hypertension
Oedema of HF, renal and liver disease
Hypokalaemia, volume depletion,
hypotension, CNS effects, GI upset,
hyperglycaemia
Carbonic
anhydrase
inhibitors
Proximal tubule Glaucoma
Diuresis in HF
Mountain sickness
Epilepsy
GI upset, urinary frequency
Potassium-
sparing
Distal tubule and
collecting duct
Adjunct for oedema of HF, liver and
renal disease
Treatment of hypokalaemia
Adjunct for hypertension
Hyperaldosteronism
Hyperkalaemia, CNS effects, diarrhoea
Osmotic
Glomerulus,
tubule
Reduction of intracranial pressure
Prevention of oliguric phase of renal
failure
Reduction of intraocular pressure
Renal clearance of toxic substances
Hypotension, GI upset, fluid and
electrolyte imbalances
