page127
ers (section 2.6.2) amlodipine,
felodipine,
or isradipine.
Use of sublingual nifedipine is not recommended.
For advice on short-term management of hypertensive
episodes
in phaeochromocytoma,
see under
Phaeo-
chromocytoma,
section 2.5.4.
2.5.1
Vasodilator
antihypertensive drugs
Vasodilators have a potent
hypotensive effect,
espe-
cially when used in combination with a beta-blocker
and a thiazide. Important: for a warning on the hazards
of a very rapid fall in blood pressure,
see Hypertensive
crises,
p.
106.
Diazoxide has been used by intravenous injection in
hypertensive emergencies,
however
alternative treat-
ments are preferred (see section 2.5)
Hydralazine is given by mouth as an adjunct to other
antihypertensives for the treatment of
resistant hyper-
tension but
is rarely used;
when used alone it
causes
tachycardia and fluid retention.
The incidence of
side-
effects is lower if the dose is kept below 100 mg daily,
but systemic lupus erythematosus should be suspected
if there is unexplained weight loss, arthritis, or any other
unexplained ill health.
Sodium nitroprusside [unlicensed]
is given by intra-
venous infusion to control
severe hypertensive emer-
gencies when parenteral treatment is necessary.
Minoxidil
should be reserved for
the treatment
of
severe hypertension resistant to other drugs.
Vasodila-
tation is accompanied by increased cardiac output and
tachycardia and the patients develop fluid retention. For
this reason the addition of a beta-blocker and a diuretic
(usually furosemide,
in high dosage)
are mandatory.
Hypertrichosis is troublesome and renders this drug
unsuitable for women.
Prazosin,
doxazosin,
and terazosin (section 2.5.4) have
alpha-blocking and vasodilator properties.
Ambrisentan,
bosentan,
iloprost,
sildenafil,
sitaxen-
tan,
and tadalafil
are licensed for
the treatment
of
pulmonary arterial
hypertension and should be used
under
specialist
supervision.
Epoprostenol
(section
2.8.1) can be used in patients with primary pulmonary
hypertension resistant to other treatments.
Bosentan is
also licensed to reduce the number of new digital ulcers
in patients with systemic sclerosis and ongoing digital
ulcer disease.
The
Scottish Medicines Consortium
(p.
4) has advised
(November 2005) that iloprost (
Ventavis
c
) is accepted
for
restricted use within NHS Scotland in patients in
whom bosentan is
ineffective or
not
tolerated,
and
should only be prescribed by specialists in the Scottish
Pulmonary Vascular Unit.
The
Scottish Medicines Consortium
(p.
4) has advised
(October 2008) that ambrisentan (
Volibris
c
) should be
prescribed only by specialists in the Scottish Pulmonary
Vascular Unit or other similar specialists.
The
Scottish Medicines Consortium
(p.
4) has advised
(January 2010)
that
sildenafil
(
Revatio
c
)
should be
prescribed only by specialists in the Scottish Pulmonary
Vascular Unit or other similar specialists.
Sitaxentan
Sitaxentan
(
Thelin
c
)
is
to
be
withdrawn
from
worldwide markets due to severe,
sometimes fatal,
hepatotoxicity;
the
benefits
of
treatment
with
sitaxentan no longer
outweigh the risks.
Patients
currently taking sitaxentan are advised not to stop
until
their
treatment
has
been reviewed by their
prescriber; patients should be switched to a suitable
alternative
as
soon
as
possible.
Patients
with
abnormal
liver
function
tests
at
the
time
of
sitaxentan
discontinuation
should
be
monitored
regularly until
liver
enzymes return to within the
normal range.
AMBRISENTAN
Indications
pulmonary arterial hypertension
Cautions
not to be initiated in significant anaemia;
monitor haemoglobin concentration or haematocrit
after 1 month and 3 months of starting treatment, and
periodically thereafter (reduce dose or discontinue
treatment if significant decrease in haemoglobin
concentration or haematocrit observed); monitor liver
function before treatment,
and monthly thereafter—
discontinue if liver enzymes raised significantly or if
symptoms of liver impairment develop
Hepatic impairment
avoid in severe impairment
Renal impairment
use with caution if eGFR less than
30 mL/minute/1.73 m
2
Pregnancy
avoid (teratogenic in
animal
studies);
exclude pregnancy before treatment and ensure
effective contraception during treatment; monthly
pregnancy tests advised
Breast-feeding
manufacturer advises avoid—no
information available
Side-effects
abdominal pain,
constipation; palpita-
tion,
flushing,
peripheral oedema;
upper respiratory-
tract disorders;
headache;
anaemia;
less commonly
hypersensitivity reactions (including angioedema and
rash)
Dose
.
ADULT
over 18 years, 5 mg once daily,
increased if
necessary to 10 mg once daily
Volibris
c
(GSK) T A
Tablets
,
f/c,
ambrisentan 5 mg (pale pink),
net price
30-tab pack = £1618.08;
10 mg (dark pink), 30-tab
pack = £1618.08
BOSENTAN
Indications
pulmonary arterial hypertension;
sys-
temic sclerosis with ongoing digital ulcer disease (to
reduce number of new digital ulcers)
Cautions
not to be initiated if systemic systolic blood
pressure is below 85 mmHg;
monitor haemoglobin
before and during treatment (monthly for first 4
months,
then 3-monthly); avoid abrupt withdrawal;
monitor liver function before treatment, at monthly
intervals during treatment,
and 2 weeks after dose
increase (reduce dose or suspend treatment if liver
enzymes raised significantly)—discontinue if symp-
toms of liver impairment;
interactions: Appendix 1
(bosentan)
Contra-indications
acute porphyria (section 9.8.2)
Hepatic impairment
avoid in moderate and severe
impairment
BNF 61
2.5.1 Vasodilator antihypertensive drugs
107
2
Cardiovascular system