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left
ventricular
pressure
during systole
resulting in
improved cardiac output.
They can also cause venous
dilatation which results
in dilatation of
capacitance
vessels,
increase of
venous pooling,
and diminution of
venous return to the heart
(decreasing left ventricular
end-diastolic pressure).
For details on the management
of
stable angina and
acute coronary syndromes,
see section 2.10.1.
2.6.1
Nitrates
Nitrates have a useful role in
angina
(for details on the
management of stable and unstable angina, see section
2.10.1). Although they are potent coronary vasodilators,
their
principal
benefit
follows
from a
reduction in
venous
return which reduces
left
ventricular
work.
Unwanted effects such as flushing,
headache,
and pos-
tural
hypotension may limit
therapy,
especially when
angina is severe or when patients are unusually sensitive
to the effects of nitrates.
Sublingual
glyceryl trinitrate is one of the most effec-
tive drugs for
providing rapid symptomatic relief
of
angina,
but
its effect
lasts only for 20 to 30 minutes;
the 300-microgram tablet
is
often appropriate when
glyceryl
trinitrate is first used.
The
aerosol
spray
pro-
vides an alternative method of rapid relief of symptoms
for
those who find difficulty in dissolving sublingual
preparations.
Duration of
action may be prolonged by
modified-release
and
transdermal
preparations (but tol-
erance may develop,
see below).
Isosorbide dinitrate is
active
sublingually
and is
a
more stable preparation for
those who only require
nitrates infrequently.
It
is also effective by mouth for
prophylaxis;
although the effect
is slower
in onset,
it
may persist for several hours. Duration of action of up to
12 hours is claimed for
modified-release
preparations.
The activity of isosorbide dinitrate may depend on the
production of active metabolites, the most important of
which is
isosorbide mononitrate.
Isosorbide mono-
nitrate itself
is also licensed for
angina prophylaxis;
modified-release formulations (for once daily adminis-
tration) are available.
Glyceryl trinitrate or isosorbide dinitrate may be tried by
intravenous injection
when the sublingual form is inef-
fective in patients with chest
pain due to myocardial
infarction or
severe ischaemia.
Intravenous injections
are also useful
in the treatment
of
congestive heart
failure.
Tolerance
Many patients on long-acting or transder-
mal
nitrates rapidly develop tolerance (with reduced
therapeutic effects). Reduction of blood-nitrate concen-
trations to low levels for 4 to 8 hours each day usually
maintains effectiveness in such patients.
If tolerance is
suspected during the use of
transdermal
patches they
should be left off for several consecutive hours in each
24 hours;
in the case of
modified-release tablets
of
isosorbide dinitrate (and conventional
formulations of
isosorbide mononitrate),
the second of
the two daily
doses should be given after about 8 hours rather than
after 12 hours. Conventional formulations of isosorbide
mononitrate should not
usually be given more than
twice daily unless
small
doses
are used;
modified-
release formulations of
isosorbide mononitrate should
only be given once daily,
and used in this way do not
produce tolerance.
GLYCERYL TRINITRATE
Indications
anal fissure (section 1.7.4);
extravasation
(section 10.3)
Sublingual:
prophylaxis and treatment of angina
Buccal:
prophylaxis and treatment of angina; adjunct
in unstable angina; acute and congestive heart failure
Injection:
control of hypertension and myocardial
ischaemia during and after cardiac surgery; induction
of controlled hypotension during surgery;
congestive
heart failure;
unstable angina
Transdermal:
see under preparations below
Cautions
hypothyroidism; malnutrition; hypothermia;
recent history of myocardial infarction;
heart failure
due to obstruction;
hypoxaemia or other ventilation
and perfusion abnormalities;
susceptibility to angle-
closure glaucoma;
metal-containing transdermal sys-
tems should be removed before magnetic resonance
imaging procedures,
cardioversion,
or diathermy;
avoid abrupt withdrawal; monitor blood pressure and
heart rate during intravenous infusion;
tolerance (see
notes above);
interactions: Appendix 1 (nitrates)
Contra-indications
hypersensitivity to nitrates;
hypo-
tensive conditions and hypovolaemia; hypertrophic
cardiomyopathy; aortic stenosis;
cardiac tamponade;
constrictive pericarditis; mitral stenosis;
toxic pulm-
onary oedema;
head trauma;
cerebral haemorrhage;
cerebrovascular disease; marked anaemia
Hepatic impairment
caution in severe impairment
Renal impairment
manufacturers advise use with
caution in severe impairment
Pregnancy
not known to be harmful
Breast-feeding
no information available—manufac-
turers advise use only if potential benefit outweighs
risk
Side-effects
postural hypotension,
tachycardia (but
paradoxical bradycardia also reported);
throbbing
headache, dizziness;
less commonly
nausea, vomiting,
heartburn, flushing, syncope, temporary hypoxaemia,
rash,
application site reactions with transdermal
patches;
very rarely
angle-closure glaucoma
Injection
Specific side-effects following injection (particu-
larly if given too rapidly) include severe hypotension,
dia-
phoresis, apprehension, restlessness,
muscle twitching,
ret-
rosternal discomfort, palpitation, abdominal pain; prolonged
administration has been associated with methaemoglobin-
aemia
Dose
. Sublingually, 0.3–1 mg, repeated as required; see also
under preparations
. By buccal administration,
see under preparation
. By intravenous infusion, 10–200 micrograms/minute,
adjusted according to response;
max.
400 micr-
ograms/minute;
consult product literature for
recommended starting doses specific to indication
.
By transdermal application,
see under preparations
Short-acting tablets and sprays
Glyceryl Trinitrate
(Non-proprietary)
Sublingual tablets
,
glyceryl trinitrate 300 micr-
ograms, net price 100 = £2.71; 500 micrograms, 100 =
£3.27;
600 micrograms,
100 = £12.31.
Label:
16
Note
Glyceryl
trinitrate tablets should be supplied in glass con-
tainers of not more than 100 tablets, closed with a foil-lined cap,
and containing no cotton wool wadding; they should be discarded
after 8 weeks in use
Aerosol spray
,
glyceryl trinitrate 400 micrograms/
metered dose,
net price 200-dose unit = £3.13
Dose
treatment or prophylaxis of angina, spray 1–2 doses under
tongue and then close mouth
BNF 61
2.6.1 Nitrates
125
2
Cardiovascular system