A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

278 NEPHROLOGICAL AND RELATED ASPECTS
absorbed through the nasal mucosa for it to be administered
intranasally. It is selective for V 2 -receptors and lacks the pressor
effect of ADH.
Desmopressin is also used for nocturnal enuresis in
children over seven years old, and intravenously in patients
with von Willebrand’s disease before undergoing elective
surgery, because it increases circulating von Willebrand factor.
It also increases factor VIII in patients with mild/moderate
haemophilia.
Key points
Volume depletion
• Volume depletion can be caused by loss of blood or
other body fluids (e.g. vomiting, diarrhoea, surgical
fistulas).
• Replacement should be with appropriate volumes of
crystalloid or blood in the case of haemorrhage.
• Excessive renal loss of salt (e.g. Addison’s disease) or
water (e.g. diabetes insipidus) can be due to renal or
endocrine disorders and requires appropriate
treatment (e.g. fludrocortisone in Addison’s disease,
desmopressin in central diabetes insipidus).
DISORDERED POTASSIUM ION BALANCE
HYPOKALAEMIA
Hypokalaemia commonly accompanies loss of fluid from the
gastro-intestinal tract (e.g. vomiting or diarrhoea), or loss of
potassium ions into the urine due to diuretic therapy (see
above). Hypokalaemia in untreated patients with hypertension
is suggestive of mineralocorticoid excess (e.g. Conn’s syndrome,
liquorice abuse). Bartter’s syndrome is a rare cause of
severe hypokalaemia that should be considered in normotensive
children who are not vomiting. Severe hypokalaemia
causes symptoms of fatigue and nocturia (because of loss of
renal concentrating ability), and can cause dysrhythmias. Mild
degrees of hypokalaemia (often associated with diuretic use)
are generally well tolerated and of little clinical importance.
Risk factors for more serious hypokalaemia include:
1. high-dose diuretics, especially combinations of loop
diuretic and thiazide;
2. other drugs that cause potassium loss/redistribution
(e.g. systemic steroids, chronic laxative treatment, high
dose β 2 -agonists);
3. low potassium intake;
4. primary or secondary hyperaldosteronism.
POTASSIUM REPLACEMENT
There are two ways to increase plasma potassium concentrations:
potassium supplements, or potassium-sparing diuretics.
POTASSIUM SUPPLEMENTS
Potassium salts may be given orally as either an effervescent or
slow-release preparation. Diet can be supplemented by foods
with a high potassium content, such as fruit and vegetables
(bananas and tomatoes are rich in potassium ions). Intravenous
potassium salts are usually given as potassium chloride. This is
used either to maintain body potassium levels in patients
receiving intravenous feeding, or to restore potassium levels in
severely depleted patients (e.g. those with diabetic ketoacidosis).
The main danger associated with intravenous potassium
is hyperkalaemia, which can cause cardiac arrest. Potassium
chloride has the dubious distinction of causing the highest frequency
of fatal adverse reactions. Potassium chloride solution
is infused at a maximum rate of 10 mmol/hour unless there is
severe depletion, when 20 mmol/hour can be given with electrocardiographic
monitoring. Particular care is needed if there
is impaired renal function. Potassium chloride for intravenous
replacement should be dilute whenever possible (e.g. mini-bags
of prediluted fluid); strong potassium solutions (the most dangerous)
should be restricted to areas such as intensive care units
where patients may need i.v. potassium while also severely
restricting fluid intake.
POTASSIUM-SPARING DIURETICS
An alternative to potassium supplementation is to combine a
thiazide or loop diuretic with a potassium-retaining diuretic
(see above). Potassium-retaining diuretics are better tolerated
than oral potassium supplements.
Key points
Disordered K metabolism
• Hypokalaemia is caused by urinary or gastro-intestinal
K loss in excess of dietary intake, or by a shift of K
into cells. Diuretics are often the cause. Endocrine
causes include Conn’s syndrome. β 2 -Agonists shift K
into cells.
• Mild hypokalaemia is often unimportant, but severe
hypokalaemia can cause dysrhythmias. Hypokalaemia
increases digoxin toxicity.
• Emergency treatment (e.g. in diabetic ketoacidosis)
involves intravenous replacement, which requires close
monitoring (including ECG).
• Foods rich in K include fruit and vegetables. Oral K
preparations are unpalatable and not very effective.
• K -retaining diuretics are used to prevent
hypokalaemia. They predispose to hyperkalaemia,
especially in patients with impaired renal function or
with concomitant use of K supplements, ACEI or
NSAIDs.
HYPERKALAEMIA
Hyperkalaemia in untreated patients suggests the possibility
of renal failure or of mineralocorticoid deficiency (e.g. Addison’s
disease). Most commonly, however, it is caused by drugs.
Hyperkalaemia can develop either with potassium supplements