page134
alpha-adrenoceptor blocking drug may also be required.
Metirosine should not be used to treat essential hyper-
tension.
PHENOXYBENZAMINE
HYDROCHLORIDE
Indications
hypertensive episodes in phaeochromo-
cytoma
Cautions
elderly;
congestive heart failure;
severe
ischaemic heart disease (see also Contra-indications);
cerebrovascular disease (avoid if history of cerebro-
vascular accident); monitor blood pressure regularly
during infusion;
carcinogenic in
animals
;
avoid in
acute porphyria (section 9.8.2);
avoid extravasation
(irritant to tissues)
Contra-indications
history of cerebrovascular acci-
dent;
during recovery period after myocardial infarc-
tion (usually 3–4 weeks); avoid infusion in hypovol-
aemia
Renal impairment
use with caution
Pregnancy
hypotension may occur in newborn
Breast-feeding
may be present in milk
Side-effects
postural hypotension with dizziness and
marked compensatory tachycardia,
lassitude,
nasal
congestion,
miosis,
inhibition of ejaculation;
rarely
gastro-intestinal disturbances;
decreased sweating
and dry mouth after intravenous infusion;
idiosyn-
cratic profound hypotension within few minutes of
starting infusion;
convulsions following rapid intra-
venous infusion also reported
Dose
. See under preparations
Phenoxybenzamine
(Goldshield) A
Injection concentrate
,
phenoxybenzamine hydro-
chloride 50 mg/mL.
To be diluted before use, net
price 2-mL amp = £57.14 (hosp.
only)
Dose
by
intravenous infusion
(preferably through large vein),
adjunct in severe shock (but rarely used) and phaeochromo-
cytoma, 1 mg/kg daily over at least 2 hours; do not repeat within
24 hours (intensive care facilities needed)
Caution
Owing to risk of contact sensitisation healthcare profes-
sionals should avoid contamination of hands
Dibenyline
c
(Goldshield) A
Capsules
,
red/white,
phenoxybenzamine hydro-
chloride 10 mg,
net price 30-cap pack = £10.84
Dose
phaeochromocytoma,
10 mg daily,
increased by 10 mg
daily;
usual dose 1–2 mg/kg daily in 2 divided doses
PHENTOLAMINE MESILATE
Indications
hypertensive episodes due to phaeo-
chromocytoma e.g.
during surgery;
diagnosis of
phaeochromocytoma (but see notes above)
Cautions
monitor blood pressure (avoid in hypo-
tension),
heart rate;
gastritis,
peptic ulcer;
elderly;
interactions: Appendix 1 (alpha-blockers)
Contra-indications
hypotension; history of myo-
cardial infarction;
coronary insufficiency,
angina,
or
other evidence of coronary artery disease
Renal impairment
manufacturer advises caution—no
information available
Pregnancy
use with caution—may cause marked
decrease in maternal blood pressure with resulting
fetal anoxia
Breast-feeding
manufacturer advises avoid—no
information available
Side-effects
postural hypotension,
tachycardia, dizzi-
ness,
flushing; nausea and vomiting,
diarrhoea,
nasal
congestion;
also acute or prolonged hypotension,
angina,
chest pain, arrhythmias
Dose
. Hypertensive episodes,
by intravenous injection,
2–
5 mg repeated if necessary
. Diagnosis of phaeochromocytoma,
consult product
literature
Rogitine
c
(Alliance) A
Injection
,
phentolamine mesilate 10 mg/mL,
net
price 1-mL amp = £1.53
Excipients
include sulphites
2.5.5
Drugs affecting the renin-
angiotensin system
2.5.5.1
Angiotensin-converting enzyme
inhibitors
2.5.5.2
Angiotensin-II receptor antagonists
2.5.5.3
Renin inhibitors
Heart failure
Drug
treatment
of
heart
failure
associated with a
reduced left ventricular ejection fraction (left ventricular
systolic dysfunction) is covered below; optimal manage-
ment
of
heart
failure with a preserved left
ventricular
ejection fraction has not been established..
The treatment of
chronic heart
failure aims to relieve
symptoms, improve exercise tolerance, reduce the inci-
dence of acute exacerbations, and reduce mortality. An
ACE inhibitor,
titrated to a ‘target dose’
(or the max-
imum tolerated dose if
lower),
together with a beta-
blocker, form the basis of treatment for all patients with
heart failure due to left ventricular systolic dysfunction.
An ACE inhibitor (section 2.5.5.1) is generally advised
for patients with asymptomatic left ventricular systolic
dysfunction or
symptomatic heart
failure.
An angio-
tensin-II receptor antagonist (section 2.5.5.2) may be
a useful
alternative for patients who,
because of
side-
effects such as cough, cannot tolerate ACE inhibitors; a
relatively
high
dose
of
the
angiotensin-II
receptor
antagonist may be required to produce benefit.
Cande-
sartan,
an angiotensin-II receptor antagonist,
can also
be added to ACE inhibitor and beta-blocker therapy in
patients with mild to moderate heart failure who con-
tinue to remain symptomatic.
The beta-blockers bisoprolol and carvedilol (section 2.4)
are of value in any grade of stable heart failure due to left
ventricular systolic dysfunction;
nebivolol
(section 2.4)
is licensed for stable mild to moderate heart failure in
patients over 70 years.
Beta-blocker treatment should
be started by those experienced in the management of
heart failure, at a very low dose and titrated very slowly
over
a period of
weeks or
months.
Symptoms
may
deteriorate initially,
calling for adjustment of
concomi-
tant therapy.
The aldosterone antagonist
spironolactone (section
2.2.3) can be considered for patients with moderate to
severe heart
failure who are already taking an ACE
inhibitor
and a beta-blocker;
low doses
of
spirono-
lactone (usually 25 mg daily)
reduce symptoms
and
mortality in these patients.
If spironolactone cannot be
114
2.5.5 Drugs affecting the renin-angiotensin system
BNF 61
2
Cardiovascular system