Pharmacology for Anaesthesia and Intensive Care

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21 Diuretics

Effects


Biochemical – hyperkalaemia is most common in patients with renal impair-

ment. Angiotensin-converting enzyme (ACE) inhibitors also predispose to hyper-

kalaemia because they reduce aldosterone secretion. It may also produce hypona-

traemia.


Hormonal – gynaecomastia in men and menstrual irregularity in women are seen

due to spironolactone’s anti-androgenic effects. It is contraindicated in Addison’s

disease.

Kinetics

Spironolactone is incompletely absorbed from the gut and highly protein bound. It

is rapidly metabolized and excreted in the urine.

Osmotic (mannitol)

The carbohydrate derivative mannitol is a polyhydric alcohol. Mannitol is used to

reduce intracranial pressure (ICP) in the presence of cerebral oedema or during

neurosurgery. It is also used to preserve peri-operative renal function in the jaundiced

patient and those undergoing major vascular surgery. It is prepared in water as a

10 or 20% solution. For the treatment of raised ICP%, the initial dose is 1 g.kg−^1 ,

which is then reduced to 0.1–0.2 g.kg−^1 .However, if the serum osmolality rises above

320 mosm.kg−^1 ,further doses of mannitol should not be given due to an increased

risk of renal failure.

Mechanism of action

Mannitol is freely filtered at the glomerulus but not re-absorbed in the tubules. It

increases the osmolality of the filtrate so that by an osmotic effect the volume of

urine is increased. It is unable to pass through an intact blood–brain barrier and by

virtue of an increased plasma osmolality it draws extracellular brain water into the

plasma. However, a head injury may give rise to a damaged blood–brain barrier. In

this situation mannitol traverses the blood–brain barrier and will drag water with it,

thereby increasing cerebral oedema.

Effects


Cardiovascular – initially circulating volume is increased producing an increased

preload and cardiac output. In susceptible patients this may precipitate heart fail-

ure.


Renal – it produces an osmotic diuresis and increased renal blood flow that may

result in a reduced intravascular volume.


Central nervous system – it produces an acute reduction in ICP, which is not sus-

tained during prolonged administration. It may also reduce the rate of formation

of cerebrospinal fluid.


Allergic – these responses occur rarely.