page103
2.1.2
Phosphodiesterase type-
3 inhibitors
Enoximone and milrinone are phosphodiesterase type-
3 inhibitors that exert most of their effect on the myo-
cardium.
Sustained haemodynamic benefit
has
been
observed after administration,
but there is no evidence
of any beneficial effect on survival.
ENOXIMONE
Indications
congestive heart failure where cardiac
output reduced and filling pressures increased
Cautions
heart failure associated with hypertrophic
cardiomyopathy,
stenotic or obstructive valvular dis-
ease or other outlet obstruction;
monitor blood pres-
sure,
heart rate,
ECG,
central venous pressure,
fluid
and electrolyte status,
renal function,
platelet count,
hepatic enzymes;
avoid extravasation;
interactions:
Appendix 1 (phosphodiesterase type-3 inhibitors)
Hepatic impairment
dose reduction may be required
Renal impairment
consider dose reduction
Pregnancy
manufacturer advises use only if potential
benefit outweighs risk
Breast-feeding
manufacturer advises caution—no
information available
Side-effects
ectopic beats;
less frequently ventricular
tachycardia or supraventricular arrhythmias (more
likely in patients with pre-existing arrhythmias);
hypotension;
also headache,
insomnia,
nausea and
vomiting,
diarrhoea;
occasionally,
chills,
oliguria,
fever,
urinary retention;
upper and lower limb pain
Dose
. By slow intravenous injection (rate not exceeding
12.5 mg/minute), diluted before use,
initially 0.5–
1 mg/kg,
then 500 micrograms/kg every 30 minutes
until satisfactory response or total of 3 mg/kg given;
maintenance,
initial dose of up to 3 mg/kg may be
repeated every 3–6 hours as required
. By intravenous infusion,
initially 90 micrograms/kg/
minute over 10–30 minutes, followed by continuous or
intermittent infusion of 5–20 micrograms/kg/minute
Total dose over 24 hours should not usually exceed
24 mg/kg
Perfan
c
(INCA-Pharm) A
Injection
,
enoximone 5 mg/mL.
For dilution before
use.
Net price 20-mL amp = £15.02
Excipients
include alcohol, propylene glycol
Note
Plastic apparatus should be used;
crystal
formation if
glass used
MILRINONE
Indications
short-term treatment of severe congestive
heart failure unresponsive to conventional mainte-
nance therapy (not immediately after myocardial
infarction);
acute heart failure,
including low output
states following heart surgery
Cautions
see under Enoximone; also correct hypo-
kalaemia;
interactions: Appendix 1 (phosphodi-
esterase type-3 inhibitors)
Renal impairment
reduce dose and monitor response
if eGFR less than 50 mL/minute/1.73 m
2
—consult
product literature for details
Pregnancy
manufacturer advises use only if potential
benefit outweighs risk
Breast-feeding
manufacturer advises caution—no
information available
Side-effects
ectopic beats,
ventricular tachycardia,
supraventricular arrhythmias (more likely in patients
with pre-existing arrhythmias), hypotension;
head-
ache;
less commonly
ventricular fibrillation,
chest
pain,
tremor,
hypokalaemia,
thrombocytopenia;
very
rarely
bronchospasm, anaphylaxis,
and rash
Dose
. By intravenous injection over 10 minutes,
either
undiluted or diluted before use, 50 micrograms/kg
followed by intravenous infusion at a rate of 375–
750 nanograms/kg/minute, usually for up to 12 hours
following surgery or for 48–72 hours in congestive
heart failure;
max.
daily dose 1.13 mg/kg
Primacor
c
(Sanofi-Aventis) A
Injection
,
milrinone (as lactate) 1 mg/mL,
net price
10-mL amp = £16.61
2.2
Diuretics
2.2.1 Thiazides and related diuretics
2.2.2 Loop diuretics
2.2.3 Potassium-sparing diuretics and
aldosterone antagonists
2.2.4 Potassium-sparing diuretics with
other diuretics
2.2.5 Osmotic diuretics
2.2.6 Mercurial diuretics
2.2.7 Carbonic anhydrase inhibitors
2.2.8 Diuretics with potassium
Thiazides (section 2.2.1)
are used to relieve oedema
due to chronic heart failure (section 2.5.5) and, in lower
doses,
to reduce blood pressure.
Loop diuretics (section 2.2.2)
are used in pulmonary
oedema due to left
ventricular failure and in patients
with chronic heart failure (section 2.5.5).
Combination diuretic therapy may be effective in
patients with oedema resistant
to treatment
with one
diuretic.
Vigorous diuresis,
particularly with loop diur-
etics, may induce acute hypotension; rapid reduction of
plasma volume should be avoided.
Elderly
Lower initial doses of diuretics should be used
in the elderly because they are particularly susceptible
to the side-effects.
The dose should then be adjusted
according to renal
function.
Diuretics should not
be
used continuously on a long-term basis to treat simple
gravitational
oedema (which will
usually respond to
increased movement,
raising the
legs,
and support
stockings).
Potassium loss
Hypokalaemia can occur with both
thiazide and loop diuretics.
The risk of
hypokalaemia
depends on the duration of action as well as the potency
and is thus greater with thiazides than with an equipo-
tent dose of a loop diuretic.
Hypokalaemia is dangerous in severe cardiovascular
disease and in patients also being treated with cardiac
glycosides. Often the use of potassium-sparing diuretics
(section 2.2.3) avoids the need to take potassium sup-
plements.
In hepatic failure, hypokalaemia caused by diuretics can
precipitate
encephalopathy,
particularly
in alcoholic
BNF 61
2.1.2 Phosphodiesterase type-3 inhibitors
83
2
Cardiovascular system