A Textbook of Clinical Pharmacology and Therapeutics

or with potassium-sparing diuretics (see above). Hyper-
kalaemia is particularly likely to occur in patients with
impaired renal function, in the elderly (in whom renal impair-
ment may be unrecognized because the plasma creatinine con-
centration is normal) and in patients receiving ACE inhibitors,
Ksupplements 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 Kinto cells.
   3.Sodium bicarbonate, given intravenously, also shifts K
   into cells.
   4.High-dose nebulized β 2 -agonists shift Kinto 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.

acidosis. It is a gastric irritant and is given as enteric-coated

tablets. The elimination of some basic drugs (e.g. amfet-

amine) is enhanced by acidification of the urine, though this is

rarely used in clinical practice.

ALKALINIZATION

Sodium bicarbonate causes urinary alkalinization; intra-

venously 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 distig-

mine) 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 inconti-

nence 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 treat-

ment 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 antimus-

carinic 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. Solifenacinis

a newer and more expensive drug.

DRUGS THATAFFECT THEBLADDER ANDGENITO-URINARYSYSTEM 279

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 Ksupplements 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 chloridegiven orally results in urinary acidifica-
tion and is used in specialized diagnostic tests of renal tubular