There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
solution
Oral suspension
CAUTIONARY AND ADVISORY LABELS 10
▶Warfarin sodium (Non-proprietary)
Warfarin sodium 1 mg per 1 ml Warfarin 1mg/ml oral suspension
sugar-free | 150 ml P £110.53 DT = £108.00
Tablet
CAUTIONARY AND ADVISORY LABELS 10
▶Warfarin sodium (Non-proprietary)
Warfarin sodium 500 microgram Warfarin 500microgram tablets |
28 tablet P £1.70 DT = £1.41
Warfarin sodium 1 mg Warfarin 1mg tablets | 28 tablet P £1.16
DT = £0.82 | 500 tablet P £9.46
Warfarin sodium 3 mg Warfarin 3mg tablets | 28 tablet P £1.20
DT = £0.86 | 500 tablet P £11.07
Warfarin sodium 5 mg Warfarin 5mg tablets | 28 tablet P £1.29
DT = £0.97 | 500 tablet P £26.79
Blood pressure conditions
4.1 Hypertension
Hypertension
Description of condition
Hypertension is defined as persistently raised arterial blood
pressure and is one of the most important treatable causes of
premature morbidity and mortality. It is a major risk factor
for stroke, myocardial infarction, heart failure, chronic
kidney disease, cognitive decline and premature death.
Hypertension is more common in advancing age, in women
aged between 65–74 years and in people of black African or
African-Caribbean origin. Other risk factors include social
deprivation, lifestyle factors, anxiety, and emotional stress.
Aims of treatment
Treatment aims to reduce the risk of cardiovascular
morbidity and mortality, including myocardial infarction and
stroke, by lowering blood pressure.
Non-drug treatment
g In patients with suspected or diagnosed hypertension,
offer lifestyle advice and support to enable patients to make
healthy lifestyle changes.
Give advice about the benefits of regular exercise, a
healthy diet, low dietary sodium intake, and reduced alcohol
intake (if excessive) as these changes can reduce blood
pressure.
Discourage excessive consumption of coffee and other
caffeine-rich products, and offer advice to help smokers to
stop smoking (see Smoking cessation p. 520). h
Hypertension thresholds for treatment
Recommendations on the management of hypertension and
blood pressure thresholds are from the National Institute for
Health and Care Excellence (NICE)—Hypertension in adults:
diagnosis and management guidelines (NG136, August 2019),
and Scottish Intercollegiate Guidelines Network (SIGN)—A
national clinical guideline: Risk estimation and the prevention
of cardiovascular disease (SIGN 149, June 2017). These
recommendations differ slightly. Recommendations are
based on NICE guidelines, and differences with SIGN (2017)
have been highlighted.
For blood pressure thresholds, targets, and the
management of hypertension in renal, diabetic or pregnant
hypertensive patients, see Hypertension in renal disease,
Hypertension in diabetes, and Hypertension in pregnancy.
g Patients presenting with a blood pressure of
140/90 mmHg or higher when measured in a clinic setting,
should be offered ambulatory blood pressure monitoring
(ABPM), or home blood pressure monitoring if ABPM is
Cardiovascular system
unsuitable, to confirm the diagnosis and stage of
hypertension. h
Stage 1 hypertension is a clinic blood pressure of
between 140/90 mmHg and 160/100 mmHg, and ambulatory
daytime average or home blood pressure average of
135/85 mmHg or higher.
g Discuss treatment options with patients aged under
80 years who have stage 1 hypertension if they have one or
more of the following: target-organ damage (for example left
ventricular hypertrophy, chronic kidney disease or
hypertensive retinopathy), established cardiovascular
disease, renal disease, diabetes, or a 10 year cardiovascular
risk 10%.
Consider antihypertensive drug treatment in addition to
lifestyle advice for adults aged under 60 with stage 1
hypertension and an estimated 10 year cardiovascular risk
10%.
Consider antihypertensive drug treatment in addition to
lifestyle advice for patients aged over 80 years with a clinic
blood pressure of over 150/90 mmHg.
For patients aged under 40 years with stage 1 hypertension
consider seeking specialist advice for evaluation of
secondary causes of hypertension.
SIGN (2017) recommend antihypertensive drug treatment
be offered to patients at high cardiovascular risk or with
evidence of cardiovascular disease, and a sustained clinic
systolic blood pressure over 140 mmHg and/or diastolic
blood pressure over 90 mmHg regardless of age. For
information about cardiovascular disease risk assessment,
see Cardiovascular disease risk assessment and prevention
p. 201. SIGN (2017) also recommend antihypertensive drug
treatment should be offered to patients who have had a
haemorrhagic or ischaemic stroke, or transient ischaemic
attack even when their baseline blood pressure is at a level
that would be considered conventionally normotensive. h
Stage 2 hypertension is a clinic blood pressure of
between 160/100 mmHg and 180/120 mmHg, and ambulatory
daytime average or home blood pressure average of
150/95 mmHg or higher.
g Treat all patients who have stage 2 hypertension,
regardless of age. h
Severe hypertension is a clinic systolic blood pressure of
180 mmHg or higher, or a clinic diastolic blood pressure of
120 mmHg or higher.
g Treat severe hypertension promptly (see Same-day
specialist referral). h
Same-day specialist referral
g If a patient has severe hypertension but no symptoms
or signs indicating same-day referral (see below), carry out
investigations for target organ damage as soon as possible. If
target organ damage is identified, consider starting
antihypertensive drug treatment immediately, without
waiting for the results of ambulatory or home blood pressure
monitoring. If no target organ damage is identified, repeat
clinic blood pressure measurement within 7 days.
Refer patients for specialist assessment, carried out on the
same day, if they have a clinic blood pressure of
180/120 mmHg and higher with signs of retinal haemorrhage
or papilloedema (accelerated hypertension), or life-
threatening symptoms for example new onset confusion,
chest pain, signs of heart failure, or acute kidney injury.
Refer patients for specialist assessment, carried out on the
same day, if they have suspected phaeochromocytoma (for
example labile or postural hypotension, headache,
palpitations, pallor, abdominal pain, or diaphoresis). h
Assessment of cardiovascular risk
g Cardiovascular risk should be estimated and assessed
for all patients with confirmed hypertension using clinic
blood pressure measurements. In these patients,glycated
Cardiovascular system
haemoglobin, electrolytes, creatinine, estimated glomular
filtration rate, total and HDL cholesterol should be
measured, tests for the presence of proteinuria, haematuria,
and hypertensive retinopathy undertaken, and a 12-lead
ECG performed.
Aspirin reduces the risk of cardiovascular events and
myocardial infarction, however high blood pressure must be
controlled before aspirin is given. Unless contra-indicated,
aspirin is recommended for all patients with established
cardiovascular disease. h
For full guidance on the risk assessment and prevention of
cardiovascular disease, see Cardiovascular disease risk
assessment and prevention p. 201.
Hypertension targets for treatment
For blood pressure thresholds, targets, and the management
of hypertension in renal, diabetic or pregnant hypertensive
patients, see Hypertension in renal disease, Hypertension in
diabetes, and Hypertension in pregnancy.
g A target clinic blood pressure below 140/90 mmHg is
suggested for patients aged under 80 years; whilst a target
clinic blood pressure below 150/90 mmHg is suggested for
patients aged over 80 years. For ambulatory or home blood
pressure monitoring (during the patient’s waking hours), a
target average of below 135/85 mmHg is suggested for
patients aged under 80 years; whilst a target average of
below 145/85 mmHg is suggested for patients aged over
80 years. SIGN (2017) instead recommend a target clinic
blood pressure below 140/90 mmHg regardless of age, whilst
patients with high cardiovascular risk and target organ
damage should aim for a clinic blood pressure below
135/85 mmHg. These figures are a general guide and may be
adapted depending on tolerability, especially in the frail or
elderly. h
Drugs for hypertension
A single antihypertensive drug is often inadequate in the
management of hypertension and additional
antihypertensive drugs are usually added in a step-wise
manner until control is achieved. g Clinicians should
ensure antihypertensive drugs are titrated to the optimum or
maximum tolerated dose at each step of treatment along
with support and discussions around adherence throughout
treatment. Response to drug treatment may be affected by
age and ethnicity.
Discuss treatment options, preferences for treatment and
individual cardiovascular disease risk with the patient.
Continue to offer lifestyle advice and support (see Non drug
treatment), whether or not they choose to start
antihypertensive drug treatment.
Clinical judgement should be used for all patients with
frailty or multimorbidity when starting antihypertensive
drug treatment.
For women with diagnosed hypertension who are
considering pregnancy or who are pregnant or breastfeeding,
manage hypertension in line with the recommendations in
the Hypertension in pregnancy section.
If an angiotensin-converting enzyme (ACE) inhibitor is not
tolerated, for example because of cough, offer an
angiotensin II receptor blocker (ARB) to treat hypertension.
The use of an ACE inhibitor with an ARB is not
recommended in the treatment of hypertension.
When choosing antihypertensive drug treatment for adults
of black African or African–Caribbean family origin, consider
an ARB, in preference to an ACE inhibitor.
If a calcium channel blocker is not tolerated, for example
because of oedema, offer a thiazide-like diuretic to treat
hypertension.
If starting or changing diuretic treatment for
hypertension, offer a thiazide-like diuretic such as
indapamide p. 178 in preference to conventional thiazide
diuretics, for example bendroflumethiazide p. 177 or
hydrochlorothiazide p. 178. Continue current treatment in
patients with hypertension who already have stable, well-
controlled blood pressure whilst on bendroflumethiazide or
hydrochlorothiazide. h
For blood pressure thresholds, targets, and the
management of hypertension in renal and diabetic patients,
see Hypertension in renal disease and Hypertension in diabetes.
Isolated systolic hypertension
g Offer patients with isolated systolic hypertension
(systolic blood pressure of160 mmHg or more) the same
treatment as patients with both raised systolic and diastolic
blood pressure. h
Hypertension with type 2 diabetes in all patients (any age or
origin), or hypertension without type 2 diabetes in those aged
55 years or below and not of black African or African-
Caribbean origin
g Step 1: Offer an ACE inhibitor or ARB.
Step 2: In addition to an ACE inhibitor or ARB, add in a
calcium channel blocker or thiazide-like diuretic. Offer a
thiazide-like diuretic if there is evidence of heart failure. h
For full guidance on the management of chronic heart
failure, see Chronic heart failure p. 204.
g Step 3: Offer an ACE inhibitor or ARB, a calcium
channel blocker and a thiazide-like diuretic.
Step 4: Before considering further treatment for a person
with resistant hypertension, confirm elevated clinic blood
pressure measurements using ambulatory or home blood
pressure recordings, assess for postural hypotension and
discuss adherence. If further treatment is required, consider
seeking specialist advice, or the addition of low dose
spironolactone [unlicensed indication] if potassium is
4.5 mmol/litre or less; or an alpha blocker or a beta blocker if
potassium is greater than 4.5 mmol/litre.
When using further diuretic therapy for step 4 treatment
of resistant hypertension, monitor blood sodium, potassium
and renal function within 1 month of starting treatment and
repeat as needed thereafter.
Seek specialist advice if blood pressure remains
uncontrolled despite taking optimal tolerated doses of 4
drugs. h
Hypertension without type 2 diabetes in patients aged 55 and
over, or all ages of black African or African-Caribbean origin
patients without type 2 diabetes
g Step 1: Offer a calcium channel blocker.
Step 2: In addition to a calcium channel blocker offer an
ACE inhibitor, ARB or a thiazide-like diuretic.
Step 3: Offer an ACE inhibitor or ARB, a calcium channel
blocker and a thiazide-like diuretic.
Step 4: Before considering further treatment for a person
with resistant hypertension, confirm elevated clinic blood
pressure measurements using ambulatory or home blood
pressure recordings, assess for postural hypotension and
discuss adherence. If further treatment is required, consider
seeking specialist advice, or consider low dose
spironolactone [unlicensed indication] if potassium is
4.5 mmol/litre or less; or an alpha blocker or a beta blocker if
potassium is greater than 4.5 mmol/litre.
When using further diuretic therapy for step 4 treatment
of resistant hypertension, monitor blood sodium, potassium,
and renal function within 1 month of starting treatment and
repeat as needed thereafter.
Seek specialist advice if blood pressure remains
uncontrolled despite taking optimal tolerated doses of 4
drugs. h
Hypertension in diabetes
g Hypertension in diabetic patients should be treated
aggressively with lifestyle modification and drug treatment.
Lowering blood pressure in patients with diabetes reduces
the risk of macrovascular and microvascular complications.
h
Hypertension in type 1 diabetes
g In type 1 diabetes, aim for a clinic blood pressure of
135/85 mmHg or less unless the adult with type 1 diabetes
has albuminuria or 2 or more features of metabolic
syndrome, in which case it should be 130/80 mmHg or less.
If drug treatment is required start a trial of a renin–
angiotensin system blocking drug as first-line treatment for
hypertension in adults with type 1 diabetes. Potential side
effects should not prevent the use of a particular class of
drug in order to control blood pressure, unless the side
effects become symptomatic or otherwise clinically
significant. In particular:
. selective beta-blockers should not be avoided where
indicated for adults on insulin;
. low-dose thiazides may be used in combination with beta-
blockers;
. calcium channel blockers (use only long-acting
preparations). h
Hypertension in type 2 diabetes
Recommendations on the management of hypertension and
blood pressure thresholds are from the National Institute for
Health and Care Excellence (NICE)—Hypertension in adults:
diagnosis and management guidelines (NG136, August 2019),
Scottish Intercollegiate Guidelines Network (SIGN)—A national
clinical guideline: Risk estimation and the prevention of
cardiovascular disease (SIGN 149, June 2017), and Scottish
Intercollegiate Guidelines Network (SIGN)—A national clinical
guideline: the management of diabetes (SIGN 116, updated
November 2017). These recommendations differ slightly.
Recommendations are based on NICE guidelines, and
differences with SIGN (2017) have been highlighted.
g SIGN (June 2017) recommend that regardless of age,
patients with high cardiovascular disease risk should be
offered antihypertensive drug treatment if clinic systolic
blood pressure is above 140 mmHg. Antihypertensive drug
treatment should also be considered even if clinic systolic
blood pressure is below 140 mmHg, with treatment targeted
at individuals thought to be at greatest risk of complications.
In type 2 diabetic patients with hypertension, NICE
recommend a clinic blood pressure below 140/90 mmHg in
those aged under 80 years, and below 150/90 mmHg in those
aged 80 years and over. SIGN (November 2017) recommend a
clinic blood pressure of 130/80 mmHg. SIGN (June 2017)
recommend a clinic blood pressure below 135/85 mmHg
regardless of age if the patient has established cardiovascular
disease. h
For the management of hypertension in patients with type
2 diabetes, see Hypertension with type 2 diabetes in all
patients (any age or origin), or hypertension without
type 2 diabetes in those aged 55 years or below and not
of black African or African-Caribbean origin in Drugs for
hypertension.
Hypertension in renal disease
Recommendations on the management of hypertension and
blood pressure thresholds are from the National Institute for
Health and Care Excellence (NICE)—Hypertension in adults:
diagnosis and management guidelines (NG136, August 2019),
and Scottish Intercollegiate Guidelines Network (SIGN)—A
national clinical guideline: Risk estimation and the prevention
of cardiovascular disease (SIGN 149 June 2017). These
recommendations differ slightly. Recommendations are
based on NICE guidelines, and differences with SIGN (2017)
have been highlighted.
g SIGN (2017) recommend that all people with stage 3
or higher chronic kidney disease, or micro- or
macroalbuminuria, or who are on dialysis should be offered
blood pressure-lowering treatment.
Cardiovascular system
A target clinic blood pressure below 140/90 mmHg is
suggested in patients with renal disease (chronic kidney
disease). A blood pressure below 130/80 mmHg is advised in
patients with chronic kidney disease and diabetes, or if urine
albumin to creatinine ratio (ACR) exceeds 70 mg/mmol).
SIGN (2017) recommend a blood pressure below
135/85 mmHg should be considered in patients with
established cardiovascular disease and chronic kidney
disease.
If possible, offer treatment with drugs taken only once a
day. h For guidance on the choice of antihypertensive
agent in patients with chronic kidney disease, see NICE
clinical guideline: Chronic kidney disease in adults (see
Useful resources).
Hypertension in pregnancy
Hypertensive disorders during pregnancy affect
approximately 8% to 10% of all pregnant women and the
complications can be associated with significant morbidity
and mortality to the mother and baby. Hypertension can
exist before pregnancy or it can be diagnosed in the first
20 weeks of gestation (known as chronic hypertension), it
can occur as new-onset of hypertension after 20 weeks
gestation (gestational hypertension) or it can occur after
20 weeks gestation with features of multi-organ involvement
(pre-eclampsia). g Pregnant women with chronic
hypertension, gestational hypertension or pre-eclampsia
should be referred to a specialist. h Symptoms of pre-
eclampsia include severe headache, problems with vision,
severe pain below ribs, vomiting and sudden swelling of
hands, feet or face accompanied with significant proteinuria
and blood pressure greater than 140/90 mmHg.
g Pregnant women are at high risk of developing pre-
eclampsia if they have chronic kidney disease, diabetes
mellitus, autoimmune disease, chronic hypertension, or if
they have had hypertension during a previous pregnancy;
these women are advised to take aspirin p. 130 [unlicensed
indication] from week 12 of pregnancy until the baby is born.
Women with more than one moderate risk factor for
developing pre-eclampsia (first pregnancy, greater than
40 years of age, pregnancy interval of greater than 10 years,
BMI above 35 kg/m2 at first visit, multiple pregnancy, or
family history of pre-eclampsia) are also advised to take
aspirin [unlicensed indication] from week 12 of pregnancy
until the baby is born.
Pregnant women with chronic hypertension who are
already receiving antihypertensive treatment should be
referred to a specialist and have their drug therapy reviewed.
Stop ACE inhibitors, ARBs, thiazide or thiazide-like diuretics
due to an increased risk of congenital abnormalities.
Women with pre-eclampsia, gestational or chronic
hypertension who present with a sustained blood pressure of
140/90 mmHg or higher should be offered antihypertensive
treatment. First-line treatment is with oral labetalol
hydrochloride p. 160 to achieve a target blood pressure of
less than 135/85 mmHg. If labetalol is unsuitable, consider
nifedipine modified-release [unlicensed] p. 174 and if
nifedipine and labetalol are both unsuitable consider
methyldopa p. 157 [unlicensed].
Women with a blood pressure of greater than
160/110 mmHg who require critical care during pregnancy or
after birth should receive immediate treatment with either
oral or intravenous labetalol hydrochloride, intravenous
hydralazine hydrochloride p. 192, or oral nifedipine
modified-release to achieve a target blood pressure of
135/85 mmHg or less.
Give intravenous magnesium sulfate p. 1112 to women in a
critical care setting with severe hypertension or severe pre-
eclampsia or if they have or have previously had an
eclamptic fit. Consider intravenous magnesium sulfate in
severe pre-eclampsia if birth is planned within 24 hours.
In women with pre-eclampsia where early birth is
Cardiovascular system
considered likely within 7 days, consider a course of
antenatal corticosteroids for fetal lung maturation.
Appropriate antihypertensive treatment should be
continued if required after birth (with dose adjustment
according to blood pressure).
Women who have been managed with methyldopa during
pregnancy should discontinue treatment within 2 days of the
birth and switch to an alternative antihypertensive.
Post-birth, advise women with hypertension that the need
to take antihypertensives does not prevent them from
breastfeeding should they wish to do so, although very low
levels of antihypertensive medicines can pass into breast
milk and most medicines are not tested in pregnant or
breastfeeding women. For women who decide to breastfeed,
offer enalapril maleate p. 180 first-line to treat hypertension
during the post-natal period, and monitor maternal renal
function and serum potassium. In women of black African or
African-Caribbean family origin consider nifedipine or
amlodipine p. 168 first line. If blood pressure is not
controlled with a single drug consider a combination of
nifedipine (or amlodipine) and enalapril. If this combination
is not tolerated or ineffective consider either adding
labetalol hydrochloride or atenolol p. 164 to the combination
treatment or swapping one of the medicines being used for
atenolol or labetalol. Blood pressure monitoring should be
considered in babies born to mothers taking
antihypertensives who are breastfeeding, and women should
be advised to monitor their babies for any adverse reactions
for example: drowsiness, lethargy, pallor, cold peripheries or
poor feeding).
Women with hypertension in the postnatal period who are
not and do not plan to breastfeed should be treated the same
way as patients in the section Drugs for hypertension.
Following birth, women remaining on antihypertensives
should have their treatment reviewed 2 weeks after the birth.
Women treated for hypertension during pregnancy should
have a medical review 6-8 weeks after birth with their GP or
specialist. h
Advanced Pharmacy Services
Patients with hypertension may be eligible for the New
Medicines Service / Medicines Use Review service provided
by a community pharmacist. For further information, see
Advanced Pharmacy Services in Medicines optimisation p. 18.
Useful Resources
Hypertension in pregnancy: diagnosis and management.
National Institute for Health and Care Excellence guideline
NG133. June 2019. www.nice.org.uk/guidance/ng133
Hypertension in adults: diagnosis and management.
National Institute for Health and Care Excellence guideline
NG136. August 2019. www.nice.org.uk/guidance/ng136
Chronic kidney disease in adults: assessment and
management. National Institute for Health and Care
Excellence guideline CG182. July 2014 (updated January
2015). www.nice.org.uk/guidance/cg182
Risk estimation and the prevention of cardiovascular
disease. Scottish Intercollegiate Guidelines Network. Clinical
guideline 149. June 2017.
www.sign.ac.uk/sign-149-risk-estimation-and-the-prevention-of-
cardiovascular-disease.html
Management of diabetes. Scottish Intercollegiate
Guidelines Network. Clinical guideline 116. March 2010
(updated November 2017).
www.sign.ac.uk/sign-116-and-154-diabetes.html
Antihypertensive drugs
Vasodilator antihypertensive drugs
Vasodilators have a potent hypotensive effect, especially
when used in combination with a beta-blocker and a
thiazide. Important: see Hypertension (hypertensive crises)
for a warning on the hazards of a very rapid fall in blood
pressure.
Hydralazine hydrochloride p. 192 is given by mouth as an
adjunct to other antihypertensives for the treatment of
resistant hypertension but is rarely used; when used alone it
causes tachycardia and fluid retention.
Sodium nitroprusside p. 193 [unlicensed] is given by
intravenous infusion to control severe hypertensive
emergencies when parenteral treatment is necessary.
Minoxidil p. 192 should be reserved for the treatment of
severe hypertension resistant to other drugs. Vasodilatation
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
p. 241, in high dosage) are mandatory. Hypertrichosis is
troublesome and renders this drug unsuitable for females.
Prazosin p. 827, doxazosin p. 826, and terazosin p. 829
have alpha-blocking and vasodilator properties.
Ambrisentan p. 195, bosentan p. 195, iloprost p. 197,
macitentan p. 196, sildenafil p. 859, and tadalafil p. 860 are
licensed for the treatment of pulmonary arterial
hypertension and should be used under specialist
supervision. Epoprostenol p. 123 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. Riociguat p. 196 is licensed for
the treatment of pulmonary arterial hypertension and
chronic thromboembolic pulmonary hypertension; it should
be used under specialist supervision.
Sitaxentan has been withdrawn from the market because
the benefit of treatment does not outweigh the risk of severe
hepatotoxicity.
Centrally acting antihypertensive drugs
Methyldopa p. 157 is a centrally acting antihypertensive; it
may be used for the management of hypertension in
pregnancy.
Clonidine hydrochloride p. 156 has the disadvantage that
sudden withdrawal of treatment may cause severe rebound
hypertension.
Moxonidine p. 157, a centrally acting drug, is licensed for
mild to moderate essential hypertension. It may have a role
when thiazides, calcium-channel blockers, ACE inhibitors,
and beta-blockers are not appropriate or have failed to
control blood pressure.
Adrenergic neurone blocking drugs
Adrenergic neurone blocking drugs prevent the release of
noradrenaline from postganglionic adrenergic neurones.
These drugs do not control supine blood pressure and may
cause postural hypotension. For this reason they have
largely fallen from use, but may be necessary with other
therapy in resistant hypertension.
Guanethidine monosulfate, which also depletes the nerve
endings of noradrenaline, is licensed for rapid control of
blood pressure, however alternative treatments are
preferred.
Alpha-adrenoceptor blocking drugs
Prazosin has post-synaptic alpha-blocking and vasodilator
properties and rarely causes tachycardia. It may, however,
reduce blood pressure rapidly after the first dose and should
be introduced with caution. Doxazosin, indoramin p. 827,
and terazosin have properties similar to those of prazosin.
Alpha-blockers can be used with other antihypertensive
drugs in the treatment of resistant hypertension.
Prostatic hyperplasia
Alfuzosin hydrochloride p. 825, doxazosin, indoramin,
prazosin, tamsulosin hydrochloride p. 828, and terazosin are
indicated for benign prostatic hyperplasia.
Drugs affecting the
renin-angiotensin system
Angiotensin-converting enzyme inhibitors
Angiotensin-converting enzyme inhibitors (ACE inhibitors)
inhibit the conversion of angiotensin I to angiotensin II.
They have many uses and are generally well tolerated. The
main indications of ACE inhibitors are shown below.
Heart failure
ACE inhibitors are used in all grades of heart failure, usually
combined with a beta-blocker. Potassium supplements and
potassium-sparing diuretics should be discontinued before
introducing an ACE inhibitor because of the risk of
hyperkalaemia. However, a low dose of spironolactone p. 206
may be beneficial in severe heart failure and can be used with
an ACE inhibitor provided serum potassium is monitored
carefully. Profound first-dose hypotension may occur when
ACE inhibitors are introduced to patients with heart failure
who are already taking a high dose of a loop diuretic (e.g.
furosemide p. 241 80 mg daily or more). Temporary
withdrawal of the loop diuretic reduces the risk, but may
cause severe rebound pulmonary oedema. Therefore, for
patients on high doses of loop diuretics, the ACE inhibitor
may need to be initiated under specialist supervision. An
ACE inhibitor can be initiated in the community in patients
who are receiving a low dose of a diuretic or who are not
otherwise at risk of serious hypotension; nevertheless, care
is required and a very low dose of the ACE inhibitor is given
initially.
Hypertension
An ACE inhibitor may be the most appropriate initial drug
for hypertension in younger Caucasian patients; Afro-
Caribbean patients, those aged over 55 years, and those with
primary aldosteronism respond less well. ACE inhibitors are
particularly indicated for hypertension in patients with type
1 diabetes with nephropathy. They may reduce blood
pressure very rapidly in some patients particularly in those
receiving diuretic therapy.
Diabetic nephropathy
ACE inhibitors have a role in the management of diabetic
nephropathy.
Prophylaxis of cardiovascular events
ACE inhibitors are used in the early and long-term
management of patients who have had a myocardial
infarction. ACE inhibitors may also have a role in preventing
cardiovascular events.
Initiation under specialist supervision
ACE inhibitors should be initiated under specialist
supervision and with careful clinical monitoring in those
with severe heart failure or in those:
. receiving multiple or high-dose diuretic therapy (e.g. more
than 80 mg of furosemide daily or its equivalent);
. receiving concomitant angiotensin-II receptor antagonist
or aliskiren;
. with hypovolaemia;
. with hyponatraemia (plasma-sodium concentration below
130 mmol/litre);
. with hypotension (systolic blood pressure below
90 mmHg);
. with unstable heart failure;
. receiving high-dose vasodilator therapy;
. known renovascular disease.
Renal effects
Renal function and electrolytes should be checked before
Cardiovascular system
starting ACE inhibitors (or increasing the dose) and
monitored during treatment (more frequently if features
mentioned below present); hyperkalaemia and other side-
effects of ACE inhibitors are more common in those with
impaired renal function and the dose may need to be
reduced. Although ACE inhibitors now have a specialised
role in some forms of renal disease, including chronic kidney
disease, they also occasionally cause impairment of renal
function which may progress and become severe in other
circumstances (at particular risk are the elderly). A specialist
should be involved if renal function is significantly reduced
as a result of treatment with an ACE inhibitor.
Concomitant treatment with NSAIDs increases the risk of
renal damage, and potassium-sparing diuretics (or
potassium-containing salt substitutes) increase the risk of
hyperkalaemia.
In patients with severe bilateral renal artery stenosis (or
severe stenosis of the artery supplying a single functioning
kidney), ACE inhibitors reduce or abolish glomerular
filtration and are likely to cause severe and progressive renal
failure. They are therefore not recommended in patients
known to have these forms of critical renovascular disease.
ACE inhibitor treatment is unlikely to have an adverse
effect on overall renal function in patients with severe
unilateral renal artery stenosis and a normal contralateral
kidney, but glomerular filtration is likely to be reduced (or
even abolished) in the affected kidney and the long-term
consequences are unknown.
ACE inhibitors are therefore best avoided in patients with
known or suspected renovascular disease, unless the blood
pressure cannot be controlled by other drugs. If ACE
inhibitors are used, they should be initiated only under
specialist supervision and renal function should be
monitored regularly.
ACE inhibitors should also be used with particular caution
in patients who may have undiagnosed and clinically silent
renovascular disease. This includes patients with peripheral
vascular disease or those with severe generalised
atherosclerosis.
ACE inhibitors in combination with other drugs
See also, Concomitant use of drugs affecting the renin-
angiotensin system, below.
Concomitant diuretics
ACE inhibitors can cause a very rapid fall in blood pressure in
volume-depleted patients; treatment should therefore be
initiated with very low doses. If the dose of diuretic is greater
than 80 mg furosemide or equivalent, the ACE inhibitor
should be initiated under close supervision and in some
patients the diuretic dose may need to be reduced or the
diuretic discontinued at least 24 hours beforehand (may not
be possible in heart failure—risk of pulmonary oedema). If
high-dose diuretic therapy cannot be stopped, close
observation is recommended after administration of the first
dose of ACE inhibitor, for at least 2 hours or until the blood
pressure has stabilised.
Combination products
Products incorporating an ACE inhibitor with a thiazide
diuretic or a calcium-channel blocker are available for the
management of hypertension. Use of these combination
products should be reserved for patients whose blood
pressure has not responded adequately to a single
antihypertensive drug and who have been stabilised on the
individual components of the combination in the same
proportions.
Angiotensin-II receptor antagonists
Azilsartan medoxomil p. 186, candesartan cilexetil p. 186,
eprosartan p. 187, irbesartan p. 187, losartan potassium
p. 187, olmesartan medoxomil p. 188, telmisartan p. 189, and
Cardiovascular system
valsartan p. 190 are angiotensin-II receptor antagonists with
many properties similar to those of the ACE inhibitors.
However, unlike ACE inhibitors, they do not inhibit the
breakdown of bradykinin and other kinins, and thus are less
likely to cause the persistent dry cough which can complicate
ACE inhibitor therapy. They are therefore a useful
alternative for patients who have to discontinue an ACE
inhibitor because of persistent cough.
An angiotensin-II receptor antagonist may be used as an
alternative to an ACE inhibitor in the management of heart
failure or diabetic nephropathy. Candesartan cilexetil and
valsartan are also licensed as adjuncts to ACE inhibitors
under specialist supervision, in the management of heart
failure when other treatments are unsuitable.
Renal effects
Angiotensin-II receptor antagonists should be used with
caution in renal artery stenosis (see also Renal effects under
Angiotensin-converting enzyme inhibitors, above).
Renin inhibitor
Aliskiren is a renin inhibitor that is licensed for the
treatment of hypertension.
Concomitant use of drugs affecting the renin-
angiotensin system
Combination therapy with two drugs affecting the renin-
angiotensin system (ACE inhibitors, angiotensin-II receptor
antagonists, and aliskiren p. 191 is not recommended due to
an increased risk of hyperkalaemia, hypotension, and renal
impairment, compared to use of a single drug. Patients with
diabetic nephropathy are particularly susceptible to
developing hyperkalaemia and should not be given an ACE
inhibitor with an angiotensin-II receptor antagonist. There
is some evidence that the benefits of combination use of an
ACE inhibitor with candesartan or valsartan may outweigh
the risks in selected patients with heart failure for whom
other treatments are unsuitable, however, the concomitant
use of this combination, together with an aldosterone
antagonist or a potassium-sparing diuretic is not
recommended.
For patients currently taking combination therapy, the
need for continued combined therapy should be reviewed. If
combination therapy is considered essential, it should be
carried out under specialist supervision, with close
monitoring of blood pressure, renal function, and
electrolytes (particularly potassium); monitoring should be
considered at the start of treatment, then monthly, and also
after any change in dose or during intercurrent illness.
Other drugs used for Hypertension Amiloride
hydrochloride, p. 243. Chlortalidone, p. 244. Co-
triamterzide, p. 245. Metolazone, p. 245. Torasemide, p. 242
. Triamterene with chlortalidone, p. 244. Xipamide, p. 245
ANTIHYPERTENSIVES, CENTRALLY ACTING
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