A Textbook of Clinical Pharmacology and Therapeutics

or with potassium-sparing diuretics (see above). Hyperkalaemia
is particularly likely to occur in patients with
impaired renal function, in the elderly (in whom renal impairment
may be unrecognized because the plasma creatinine concentration
is normal) and in patients receiving ACE inhibitors,
K � supplements or NSAID.
Treatment
1. Calcium gluconate is a potentially life-saving emergency
treatment in patients with dysrhythmias caused by
hyperkalaemia (Chapter 32). It is given intravenously
with ECG monitoring.
2. Glucose and insulin shift extracellular K� into cells.
3. Sodium bicarbonate, given intravenously, also shifts K� into cells.
4. High-dose nebulized β2-agonists shift K� into cells.
5. Ion-exchange resin made of sodium or calcium
polystyrene sulphonate removes potassium from the body
in stool. The main adverse effect when resins are given
chronically for patients with chronic renal failure is
constipation, which can be avoided if the resins are
suspended in a solution of sorbitol.
6. Emergency haemofiltration or dialysis.
Key points
Drugs and plasma potassium
• Hypokalaemia (and hypomagnesaemia) predisposes to
digoxin toxicity and to torsades de pointes caused by
drugs that prolong the QT interval (e.g. amiodarone,
sotalol). Mild hypokalaemia associated with thiazide or
loop diuretics is common and seldom harmful per se.
• Where hypokalaemia is clinically important it can be
corrected and/or prevented with K � supplements or
more conveniently with K � -retaining diuretics.
However, these predispose to hyperkalaemia.
• Hyperkalaemia can cause dysrhythmias that can be
fatal. ACEI predispose to hyperkalaemia, especially
when there is renal impairment.
• Emergency treatment of broad complex tachycardia
caused by hyperkalaemia includes i.v. calcium
gluconate.
• Glucose and insulin i.v. cause redistribution of
potassium into cells.
• Sodium bicarbonate i.v. can cause redistribution of
potassium into cells in exchange for hydrogen ions.
• β 2-Agonists i.v./high-dose nebulized cause intracellular
shift of K � .
• Haemodialysis or haemofiltration is frequently
indicated in acute hyperkalaemic emergencies.
• Ion-exchange resins administered by mouth are useful.
DRUGS THAT ALTER URINE pH
ACIDIFICATION
Ammonium chloride given orally results in urinary acidification
and is used in specialized diagnostic tests of renal tubular
DRUGS THAT AFFECT THE BLADDER AND GENITO-URINARY SYSTEM 279
acidosis. It is a gastric irritant and is given as enteric-coated
tablets. The elimination of some basic drugs (e.g. amfetamine)
is enhanced by acidification of the urine, though this is
rarely used in clinical practice.
ALKALINIZATION
Sodium bicarbonate causes urinary alkalinization; intravenously
it is used to alkalinize the urine in salicylate overdose
(see Chapter 54). However, if given by mouth it reacts with
hydrochloric acid in the stomach to produce carbon dioxide, so
it is poorly tolerated and not very effective. Instead, a citric
acid/potassium citrate mixture can be used orally, as citrate is
absorbed from the gut and metabolized via the tricarboxylic
acid cycle with generation of bicarbonate. Potassium must be
avoided in renal failure, as retention of potassium ions may
cause hyperkalaemia.
Use
Alkalinization of the urine is used to give symptomatic relief
for the dysuria of cystitis and to prevent the formation of uric
acid stones, especially in patients who are about to undergo
cancer chemotherapy. The use of alkaline diuresis to increase
urinary excretion of salicylate following overdose is discussed
in Chapter 54.
DRUGS THAT AFFECT THE BLADDER AND
GENITO-URINARY SYSTEM
DRUGS TO INCREASE BLADDER ACTIVITY
Drugs that increase bladder activity (e.g. muscarinic agonists,
such as bethanechol, or anticholinesterases, such as distigmine)
have been used to treat patients with chronic retention
of urine, but catheterization is usually preferable.
DRUGS FOR URINARY INCONTINENCE
Stress incontinence is usually managed without drugs, often
surgically, although duloxetine (an amine uptake inhibitor) is
licensed for use in women with moderately severe stress
incontinence in conjunction with pelvic floor exercises. Alpha
blockers (e.g. doxazosin, see Chapter 28) can worsen incontinence
in women with pelvic floor pathology and should be
discontinued if possible.
Urge incontinence is common. Infection should be excluded.
When unstable detrusor contraction is responsible, drug treatment
to reduce bladder activity is of limited use, combined with
pelvic floor exercises and bladder training. Antimuscarinic
drugs, such as oxybutynin, have a high incidence of antimuscarinic
side effects (e.g. dry mouth, dry eyes, blurred vision,
constipation, confusion). These may be minimized by starting
with a low dose and by slow release formulation. Solifenacin is
a newer and more expensive drug.