page104
cirrhosis;
diuretics can also increase the risk of
hypo-
magnesaemia in alcoholic cirrhosis,
leading to arrhyth-
mias. Spironolactone, a potassium-sparing diuretic (sec-
tion 2.2.3),
is chosen for oedema arising from cirrhosis
of the liver.
Potassium supplements or potassium-sparing diuretics
are seldom necessary when thiazides are used in the
routine treatment
of
hypertension (see also section
9.2.1.1).
2.2.1
Thiazides and related
diuretics
Thiazides
and
related
compounds
are
moderately
potent
diuretics;
they inhibit
sodium reabsorption at
the beginning of the distal convoluted tubule.
They act
within 1 to 2 hours of oral administration and most have
a duration of action of 12 to 24 hours;
they are usually
administered early in the day so that the diuresis does
not interfere with sleep.
In the management
of
hypertension
a low dose of
a
thiazide,
e.g.
bendroflumethiazide 2.5 mg daily,
pro-
duces a maximal
or near-maximal
blood pressure low-
ering effect,
with very little biochemical
disturbance.
Higher doses cause more marked changes in plasma
potassium,
sodium,
uric acid,
glucose,
and lipids,
with
little advantage in blood pressure control. For reference
to the use of thiazides in chronic heart failure see section
2.5.5.
Bendroflumethiazide is widely used for mild or mod-
erate heart
failure and for hypertension—alone in the
treatment of
mild hypertension or with other drugs in
more severe hypertension.
Chlortalidone,
a
thiazide-related compound,
has
a
longer duration of
action than the thiazides and may
be given on alternate days to control oedema. It is also
useful if acute retention is liable to be precipitated by a
more rapid diuresis or
if
patients dislike the altered
pattern of micturition caused by other diuretics.
Other
thiazide diuretics (including benzthiazide,
clop-
amide,
cyclopenthiazide,
hydrochlorothiazide,
and
hydroflumethiazide) do not offer any significant advan-
tage over bendroflumethiazide or chlortalidone.
Metolazone is particularly effective when combined
with a loop diuretic (even in renal
failure);
profound
diuresis can occur and the patient should therefore be
monitored carefully.
Xipamide and indapamide are chemically related to
chlortalidone.
Indapamide is claimed to lower
blood
pressure with less metabolic disturbance,
particularly
less aggravation of diabetes mellitus.
Cautions
See also section 2.2.
Thiazides and related
diuretics can exacerbate diabetes,
gout,
and systemic
lupus erythematosus. Electrolytes should be monitored,
particularly with high doses,
long-term use,
or in renal
impairment. Thiazides and related diuretics should also
be used with caution in nephrotic syndrome, hyperaldo-
steronism,
and malnourishment;
interactions:
Appen-
dix 1 (diuretics)
Contra-indications
Thiazides and related diuretics
should be avoided in refractory hypokalaemia,
hypo-
natraemia and hypercalcaemia, symptomatic hyperuric-
aemia,
and Addison’s disease.
Hepatic impairment
Thiazides and related diuretics
should be used with caution in mild to moderate impair-
ment and avoided in severe liver disease. Hypokalaemia
may precipitate coma,
although hypokalaemia can be
prevented by using a potassium-sparing diuretic.
There
is an increased risk of
hypomagnesaemia in alcoholic
cirrhosis.
Renal impairment
Thiazides and related diuretics are
ineffective if
eGFR is less than 30 mL/minute/1.73 m
2
and should be avoided;
metolazone remains effective
but with a risk of excessive diuresis.
Pregnancy
Thiazides and related diuretics should not
be used to treat
gestational
hypertension.
They may
cause neonatal
thrombocytopenia,
bone marrow sup-
pression,
jaundice,
electrolyte disturbances,
and hypo-
glycaemia;
placental
perfusion may also be reduced.
Stimulation of
labour,
uterine inertia,
and meconium
staining have also been reported.
Breast-feeding
The amount of bendroflumethiazide,
chlortalidone,
cyclopenthiazide,
and metolazone pre-
sent
in milk is too small
to be harmful;
large doses
may suppress lactation.
For indapamide and xipamide
see individual drugs.
Side-effects
Side-effects of thiazides and related diur-
etics include mild gastro-intestinal disturbances, postur-
al
hypotension,
altered plasma-lipid concentrations,
metabolic and electrolyte disturbances including hypo-
kalaemia (see also notes above),
hyponatraemia,
hypo-
magnesaemia,
hypercalcaemia,
hyperglycaemia,
hypo-
chloraemic alkalosis,
hyperuricaemia,
and gout.
Less
common side-effects include blood disorders such as
agranulocytosis,
leucopenia,
and
thrombocytopenia,
and impotence.
Pancreatitis,
intrahepatic cholestasis,
cardiac arrhythmias,
headache,
dizziness,
paraesthesia,
visual
disturbances,
and
hypersensitivity
reactions
(including
pneumonitis,
pulmonary
oedema,
photo-
sensitivity,
and severe skin reactions)
have also been
reported.
BENDROFLUMETHIAZIDE
(Bendrofluazide)
Indications
oedema, hypertension (see also notes
above)
Cautions
see notes above
Contra-indications
see notes above
Hepatic impairment
see notes above
Renal impairment
see notes above
Pregnancy
see notes above
Breast-feeding
see notes above
Side-effects
see notes above
Dose
. Oedema, initially 5–10 mg daily in the morning
or
on
alternate days; maintenance 5–10 mg 1–3 times
weekly
. Hypertension,
2.5 mg daily in the morning;
higher
doses rarely necessary (see notes above)
Bendroflumethiazide
(Non-proprietary) A
Tablets
,
bendroflumethiazide 2.5 mg,
net price 28 =
79p;
5 mg,
28 = 86p
Brands include
Aprinox
c
84
2.2.1 Thiazides and related diuretics
BNF 61
2
Cardiovascular system