814
P A R T 9
Drugs acting on the renal system
gynaecomastia, deepening of the voice and irregular
menses.
Clinically important drug–drug interactions
The diuretic effect decreases if potassium-sparing diu-
retics are combined with salicylates. Dose adjustment
may be necessary to achieve therapeutic effects.
molecule. Because the tubule is not able to reabsorb all
of the sugar pulled into it, large amounts of fluid are lost
in the urine. The effects of these osmotic drugs are not
limited to the kidneys because the injected substance pulls
fluid into the vascular system from extravascular spaces,
including the aqueous humour. Therefore, these drugs
are often used in acute situations when it is necessary to
decrease intraocular pressure before eye surgery or during
acute attacks of glaucoma. They also are the diuretics
of choice in cases of increased cranial pressure or acute
renal failure due to shock, drug overdose or trauma. See
Table 51.2 for usual indications for each of these agents.
Pharmacokinetics
Mannitol is only available for intravenous use. This drug
is freely filtered at the renal glomerulus, poorly reab-
sorbed by the renal tubule, not secreted by the tubule
and resistant to metabolism. Its action depends on the
concentration of the osmotic activity in the solution. It is
not known whether it can cause fetal harm. In addition,
the effects of mannitol during breastfeeding are not well
understood.
Contraindications and cautions
These drugs are contraindicated in individuals with
renal disease and anuria from severe renal disease, pul-
monary congestion, intracranial bleeding, dehydration
avocados
bananas
broccoli
cantaloupe
dried fruits
grapefruit
lima beans
navy beans
nuts
oranges
peaches
potatoes
prunes
rhubarb
spinach
sunflower seeds
tomatoes
watermelon
■■
BOX 51.2
Potassium-rich foods
Prototype summary: Spironolactone
Indications:
Primary hyperaldosteronism, adjunctive
therapy in the treatment of oedema associated
with HF, nephrotic syndrome, hepatic cirrhosis;
treatment of hypokalaemia or prevention
of hypokalaemia in people at high risk if
hypokalaemia occurs; essential hypertension.
Actions:
Competitively blocks the effects of
aldosterone in the renal tubule, causing loss of
sodium and water and retention of potassium.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
24–48 hours 48–72 hours 48–72 hours
T
1/2
:
20 hours; metabolised in the liver and excreted
in urine.
Adverse effects:
Dizziness, headache, drowsiness,
rash, cramping, diarrhoea, hyperkalaemia,
hirsutism, gynaecomastia, deepening of the voice,
irregular menses.
O
smotic diuretics
Osmotic diuretics pull water into the renal tubule
without sodium loss. The osmotic diuretics include
glucose and mannitol (
Osmitrol
).
Therapeutic actions and indications
Some non-electrolytes are used intravenously to increase
the volume of fluid produced by the kidneys. Mannitol,
for example, is a sugar that is not well reabsorbed by
the tubules; it acts to pull large amounts of fluid into the
urine due to the
osmotic pull
exerted by the large sugar
Prototype summary: Mannitol
Indications:
Prevention and treatment of the oliguric
phase of renal failure; reduction of intracranial
pressure and treatment of cerebral oedema; reduction
of elevated intraocular pressure; promotion of
urinary excretion of toxic substances; diagnostic use
for measurement of glomerular filtration rate; also
available as an irrigant in transurethral prostatic
resection and other transurethral procedures.
Actions:
Elevates the osmolarity of the glomerular
filtrate, leading to a loss of water, sodium and
chloride; creates an osmotic gradient in the eye,
reducing intraocular pressure; creates an osmotic
effect that decreases swelling after transurethral
surgery.
Pharmacokinetics:
Route
Onset
Peak
Duration
IV
30–60 mins 1 hour
6–8 hours
Irrigant
Rapid
Rapid Short
T
1/2
:
15–100 minutes; excreted unchanged in urine.
Adverse effects:
Dizziness, headache, hypotension,
rash, nausea, anorexia, dry mouth, thirst, diuresis,
fluid and electrolyte imbalances.
