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9780521704632c21 CUFX213A/Peck 9780521618168 December 28, 2007 14:15
Section IVOther important drugs
Miscellaneous – deafness occasionally follows rapid administration of a large dose
and is more common in patients with renal failure, and those on aminoglycoside
therapy. Bumetanide is less ototoxic than furosemide but may also cause myalgia.
Interactions – lithium levels may rise when given with loop diuretics.Kinetics
Both furosemide and bumetanide are well absorbed from the gut although their oral
bioavailability is different (65% and 95% respectively). Both drugs are highly plasma
protein bound (>95%) and excreted largely unchanged in the urine.Potassium sparing (amiloride)
Amiloride is a weak diuretic that is frequently used in combination with loop diuretics
to prevent hypokalaemia.Mechanism of action
Atthe distal convoluted tubule it blocks Na+/K+exchange, creating a diuresis, and
decreasing K+excretion.Effects
Metabolic – hyperkalaemia may sometimes follow its use. The hypokalaemic,
hypochloraemic metabolic alkalosis seen with thiazide and loop diuretics is not a
feature of K+sparing diuretics.Kinetics
Amiloride is poorly absorbed from the gut, minimally protein bound and not metab-
olized.Aldosterone antagonists (spironolactone)
Spironolactone is only available as an oral preparation. Potassium canrenoate is
available parenterally and is metabolized to canrenone, which is also a metabolite
of spironolactone.
Owing to its mode of action its effects take a few days to become established. It is
used to treat ascites, nephrotic syndrome and primary hyperaldosteronism (Conn’s
syndrome).Mechanism of action
Spironolactone is a competitive aldosterone antagonist. Normally aldosterone stim-
ulates the reabsorption of Na+in the distal tubule, which provides the driving force
for the excretion of K+.When aldosterone is antagonized, K+excretion is significantly
reduced while increased Na+excretion produces a diuresis. The diuresis produced
is limited as only 2% of Na+reabsorption is under the control of aldosterone.