BJA Education, 15 (6): 280–285 (2015)
doi: 10.1093/bjaceaccp/mku061
Matrix reference, 1A02
Antihypertensive drugs
RE Jackson BSc MB ChB FRCA1 and MC Bellamy MB BS MA FRCA FRCP (Edin)
FFICM2, *
1
Specialty Registrar in Anaesthesia, St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK, and
2
Professor, Intensive Care Unit, St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK
*To whom correspondence should be addressed. Tel: +44 113 206 5789; E-mail: m.c.bellamy@leeds.ac.uk
Key points
• Antihypertensive drugs are frequently used by pa-
tients and may influence conduct of anaesthesia.
• Relatively few drug classes are used to treat hyperten-
sion, the newest of which are direct renin inhibitors.
• The renin–angiotensin system is targeted at differ-
ent points by many of the commonly used antihy-
pertensive drugs.
• Antihypertensive drugs have diverse indications,
both cardiac and non-cardiac.
• Guidance on antihypertensive agents is provided by
the National Institute for Health and Care Excellence.
Antihypertensive drugs comprise several classes of compound
with the therapeutic intention of preventing, controlling, or
treating hypertension. The classes of antihypertensive drug
differ both structurally and functionally. They are important in
anaesthetic practice because they are commonly prescribed to
the general population, with the overall prevalence of hyperten-
sion being 31% in the UK [defined by the National Institute for
Health and Care Excellence (NICE) as a measurement of 140/90
mm Hg or higher in clinic, with subsequent ambulatory or
home measurement of 135/85 mm Hg or higher].1 Antihyperten-
sive drugs are used frequently in other unrelated conditions, for
example, β-blockers in thyrotoxicosis and anxiety, or angioten-
sin-converting enzyme inhibitors (ACEIs) in heart failure. Hence
both the drug and its indication are relevant to the conduct of
anaesthesia.
This article focuses on the applied pharmacology of agents
commonly encountered in UK clinical practice, their therapeutic
and side-effects, drug interactions, and implications for
© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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anaesthesia and surgery. The causes of hypertension are sum-
marized in Table 1.
Pharmacological management of hypertension
The majority of hypertensive patients have primary (or essential)
hypertension, that is, hypertension in which secondary causes
are not present. Management aims to control arterial pressure,
prevent end-organ damage (cerebrovascular, cardiovascular,
and renal), and reduce the risk of premature death.1
Arterial pressure may be lowered by reducing cardiac out-
put, systemic vascular resistance (SVR), or both (Fig. 1). Drugs
manipulating SVR may also bring about clinical improvement
through modification of vascular compliance and reactivity.
For example, the β-blockers carvedilol and atenolol reduce arter-
ial pressure similarly at rest, but carvedilol is associated with
improved vascular compliance.
Drugs may be classified by mechanism or site of action.2
Within each class, there are multiple drugs with structural and
pharmacological variations resulting in differing therapeutic
and side-effects (Table 2). Many agents do not have a ‘clean’
mechanism of action, but act on multiple pathways.
Antihypertensives may be divided into two broad groups,3 the
first group being those which directly or indirectly block the
renin–angiotensin system (RAS), for example, ACEIs, angiotensin
receptor antagonists (ARAs), direct renin inhibitors (DRIs), and to
a lesser extent β-blockers. While these drugs have multiple me-
chanisms of action, their predominant effect is to cause vasodila-
tation. The second group of drugs works by increasing water and
sodium excretion, thereby reducing intravascular volume, or by
causing vasodilatation through non-RAS pathways, for example,
diuretics and calcium channel blockers (CCBs). The actions of this
second group increase RAS activity through negative feedback, a
result of which is that they can potentiate the activity of drugs
which target and inhibit the RAS.
280

The appropriate choice of antihypertensive drug depends on
which groups of drugs are most likely to be effective both in con-
trolling arterial pressure and in preventing complications such as
end-organ damage. Current NICE guidance recommends that pa-
tients under the age of 55 be initiated on drugs which target the
RAS as first-line therapy. Patients aged over 55 and black people
of African or Caribbean family origin are initially treated with
drugs which act through non-RAS mechanisms, as these latter
patient groups typically have low-renin hypertension. Addition-
ally, there may be compelling individual indications or contrain-
dications for the use of a particular drug class.1
Drugs which target the RAS
Three drug classes directly target points of the RAS pathway.
They act to reduce production of the peptide hormone
Table 1 Summary of causes of hypertension
Primary (essential hypertension)
Secondary
Renal Polycystic kidney disease; chronic kidney disease;
urinary tract obstruction; renin-secreting
tumour
Vascular Renovascular disease; vasculitis; coarctation of
the aorta; collagen disorders
Hormonal
Endogenous Hyperaldosteronism; phaeochromocytoma;
Cushing’s syndrome; congenital adrenal
hyperplasia; hyper/hypothyroidism;
hyperparathyroidism; excess growth hormone;
hypercalcaemia
Exogenous Steroids; oral contraceptive pill
Neurogenic Space-occupying lesion; intracranial
hypertension
Toxins Alcohol; non-steroidal anti-inflammatory drugs;
adrenoceptor agonists; liquorice
Others Obstructive sleep apnoea; pregnancy induced;
pre-eclampsia
Fig 1 Overview of the mechanisms of action of common classes of antihypertensive drugs. There may be considerable overlap between some of the groups, for instance,
thiazide and loop diuretics cause vasodilatation and diuresis.
Antihypertensive drugs
angiotensin II, or reduce its receptor binding (Fig. 2). Angiotensin
II has high affinity for AT1 G-protein-coupled receptors, activa-
tion of which causes increased arteriolar tone and SVR. It also
causes sympathetic nervous system activation, increased pituit-
ary secretion of antidiuretic and adrenocortocotrophic hor-
mones, and increased adrenocortical secretion of aldosterone.4
By antagonizing the RAS pathway, SVR and arterial pressure are
reduced. This effect is potentiated by a reduction in aldosterone
secretion with resultant reduction in renal sodium and water re-
tention. Negative feedback results in increased renin release by
the juxtaglomerular apparatus.
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ACEI drugs
The discovery that the venom of the Brazilian pit viper, which
causes a massive decrease in arterial pressure, works by inhib-
ition of angiotensin-converting enzyme (ACE) led to the develop-
ment of synthetic, orally administered ACEIs.
ACEIs are first-line treatment in patients under 55 yr old with
primary hypertension.1 They are also indicated in heart failure,
post-myocardial infarction, diabetic nephropathy, and chronic
kidney disease (although not acute kidney injury). The renal
and cardiac protective effects of ACEIs are greater than those ex-
pected by arterial pressure control alone.5
ACE is a metallopeptidase enzyme which occurs mainly with-
in the pulmonary vasculature. The inhibition of ACE reduces the
cleavage of the peptide hormone angiotensin I to angiotensin II
and reduces metabolism of the peptide bradykinin to inactive
substances. The reduction in angiotensin II is responsible for
most of the therapeutic effects. The accumulation of bradykinin
has some therapeutic advantage through vasodilatation, but is
also responsible for a dry cough in susceptible individuals.
ACEIs can also precipitate renal dysfunction by decreasing renal
efferent arteriolar tone, thereby decreasing effective renal perfu-
sion pressure, a particular risk in renal artery stenosis. Other
side-effects include hyperkalaemia due to reduced aldosterone
secretion, agranulocytosis, skin rashes, and taste disturbance.
A rare idiosyncratic reaction to ACEIs can cause angiooedema
BJA Education | Volume 15, Number 6, 2015 281
Antihypertensive drugs

with potential upper airway obstruction; this can occur several
years after initiation of ACEI therapy. ACEIs are contraindicated
in pregnancy as they are associated with birth defects.
ACEIs are administered orally with the exception of i.v.
enalaprilat (the active form of enalapril). Enalapril, ramipril,
and perindopril are prodrugs requiring hepatic esterification
for activation. Captopril is an active drug converted to active
metabolites by the liver. Lisinopril is an active drug, excreted
unchanged. Most ACEIs are excreted predominantly by the
kidney.
ACEIs may interact with drugs used perioperatively. For ex-
ample, non-steroidal anti-inflammatory drugs can precipitate
renal dysfunction in combination with ACEIs. They can also re-
duce the efficacy of ACEIs by decreasing prostaglandin synthesis.
Interactions with diuretics may cause hypovolaemia and hypo-
natraemia, while concurrent use of potassium supplements or
potassium-sparing diuretics may result in hyperkalaemia.
Drugs which are renally excreted (e.g. digoxin and lithium) may
accumulate in patients taking ACEIs.
There is increased risk of hypotension on induction of anaes-
thesia in patients who have recently taken an ACEI, which may
necessitate the use of vasopressor drugs in order to restore arter-
ial pressure.6 7 To date, there is no high level evidence of worse
clinical outcomes in patients who have taken ACEIs on the day

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of surgery.

Table 2 Classes and subclasses of antihypertensive medications with

common examples ARA drugs
ARAs are commonly used in patients who are intolerant of ACEIs
Class Examples
as they are less likely to cause a dry cough. The therapeutic and
Targeting renin–angiotensin system side-effects are broadly similar to those of ACEIs, with evidence
Angiotensin-converting Captopril, lisinopril, ramipril of reduced risk of new onset diabetes, stroke, progression of car-
enzyme inhibitors diac failure, and all-cause mortality in patients with chronic kid-
Angiotensin receptor Candesartan, losartan, valsartan ney disease.
antagonists ARAs are orally administered drugs which target AT1 G-pro-
Direct renin antagonists Aliskiren tein-coupled receptors to antagonize the effect of the peptide
Adrenoceptor antagonists hormone angiotensin II. Some drugs (candesartan and telmisar-
β-Blockers Atenolol, metoprolol, propranolol tan) bind irreversibly, while others (losartan and valsartan) are
α-Blockers Doxazosin, labetalol (also a β-blocker), competitive antagonists.
phentolamine, phenoxybenzamine Direct targeting of angiotensin II receptors has theoretical ad-
Calcium channel blockers vantages over ACE inhibition. Angiotensin II may be produced
Phenylalkamines Verapamil through non-ACE pathways, for example, by the enzyme chy-
Dihydropyridines Amlodipine, nifedipine, nimodipine mase in kidney tissue, which is not affected by ACEIs. ARAs do
Benzothiazepines Diltiazem not inhibit bradykinin metabolism, and therefore, the incidence
Diuretics
of cough is much less than with ACEIs. The risk of angiooedema is
Thiazides Bendroflumethiazide,
greatly reduced with ARAs compared with ACEIs.
hydrochlorothiazide
As with ACEIs, patients taking ARAs are at increased risk of
Loop Furosemide, bumetanide
episodes of hypotension after induction of anaesthesia, particu-
Potassium sparing/ Amiloride, spironolactone
larly when taken in combination with diuretics.7
aldosterone antagonist
Vasodilators Hydralazine, minoxidil
Centrally acting agents Clonidine, methyldopa
Ganglion block Trimetaphan

Fig 2 Sites of action of drugs affecting the renin–angiotensin system. ACEI, angiotensin-converting enzyme inhibitor. ARB, angiotensin receptor blocker.

282 BJA Education | Volume 15, Number 6, 2015


Direct renin inhibitors
Aliskiren, a piperidine derivative, is the only available drug in this
class and is used by specialists in patients who are unresponsive
to, or intolerant of, other antihypertensives. Aliskiren directly
inhibits the enzyme renin, which is secreted by granular cells
of the juxtaglomerular apparatus. Renin inhibition reduces the
conversion of the hepatically secreted polypeptide angiotensino-
gen to angiotensin I. Its effect on the RAS is therefore ‘upstream’
of ACEIs and ARAs and it does not cause bradykinin accumula-
tion. DRIs have the same potential to cause renal dysfunction
and electrolyte disturbances as ACEIs and ARAs. Diarrhoea is a
specific side-effect to higher doses of DRIs.
Aliskiren is orally administered, although it is poorly absorbed
and its bioavailability is low (2.7%); therefore, therapeutic plasma
concentration is only achieved by repeat dosing. It is minimally
metabolized and its main route of elimination is biliary. There-
fore, it has a long elimination half-life (24–40 h).3
Aliskiren may have a larger role in the management of
hypertension in future, possibly in combination with other
drugs. Evidence relating to the implications of aliskiren therapy
on anaesthetic conduct is limited, although there are case reports
of patients having prolonged and refractory hypotension after
induction of general anaesthesia.
Should drugs which target the RAS be used
perioperatively?
There are currently no universal guidelines on whether RAS-
blocking drugs should be withheld before surgery. However, in
many departments, local guidelines recommend that ACEIs
and ARAs be withheld on the day of surgery in order to reduce
the risk of hypotension and organ hypoperfusion under anaes-
thesia. This approach should be balanced against the potential
beneficial effects of continuing these drugs perioperatively.
Some authors recommend that patients with heart failure or
resistant hypertension continue to take ACEIs perioperatively.
The potential benefits of this approach may outweigh the risks,
provided care is taken to maintain euvolaemia and episodes of
hypotension are managed with volume expansion and vasopres-
sors. Other described benefits of continuing RAS antagonists in
the perioperative period include renal protection, reduced rates
of perioperative atrial fibrillation, and neuroprotection in cere-
brovascular surgery.8
Adrenoceptor antagonists
β-Blockers
β-Blockers are not used as first-line antihypertensives unless
there are other indications, for example, after myocardial infarc-
tion, or in tachyarrhythmias such as atrial fibrillation. Their
diverse indications include stable heart failure, thyrotoxicosis,
oesophageal varices, anxiety, and glaucoma.
β-Blockers antagonize catecholamines at β-adrenoceptors.
These Gs type G-protein-coupled receptors are classified as β1,
present mainly within the heart and kidneys; and β2, present
throughout the body in lungs, blood vessels, and muscle. The re-
duction in arterial pressure achieved by β-blockers is attributable
to their effects upon multiple pathways. Block of β1 receptors in
the sinoatrial node reduces heart rate and block of myocardial re-
ceptors reduces contractility (reduced chronotropy and inotropy,
respectively). They also reduce sympathetic nervous system
activity, while block of receptors in the juxtaglomerular appar-
atus reduces renin secretion.
Antihypertensive drugs
β-Blockers are categorized according to cardioselectivity.
Metoprolol, esmolol, and atenolol have greater affinity for β1
receptors than β2 at therapeutic doses (selectivity is reduced at
higher doses). This contrasts with non-cardioselective drugs
such as propranolol and sotalol. Most β-blockers are pure antago-
nists; however, some drugs are partial antagonists at β receptors
and exhibit some agonist/sympathetomimetic activity ( pindolol,
timolol). The clinical relevance of this is uncertain. Some β-
blockers ( propranolol, metoprolol) block sodium channels and
have membrane stabilizing activity, that is, may be classed as
Vaughan-Williams class 1 antiarrhythmics. Labetalol is a
β-blocker which also has α-blocking activity. In addition to their
antihypertensive effects, β-blockers improve the myocardial oxy-
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gen supply:demand ratio and help reduce myocardial ischaemia
by prolonging the period of diastole. While β-blockers are used in
stable heart failure, they have the potential to worsen symptoms
in some patients by reducing cardiac output. Poor peripheral
circulation and Raynaud’s phenomenon may be precipitated
both by reduced cardiac output and block of peripheral β2 recep-
tors. Bronchospasm caused by β2 block may be a significant
respiratory side-effect in susceptible individuals, for example,
asthmatics. Central nervous system effects include malaise,
tiredness, and vivid dreams, particularly with lipid-soluble
drugs. In insulin-dependent diabetic patients, the symptoms of
hypoglycaemia may be suppressed by sympathetic block.
More than 30 β-blockers are currently available. Oral adminis-
tration is common as most have good absorption and bioavail-
ability. I.V. preparations are available for some, including
atenolol, metoprolol, and esmolol. Lipid-soluble drugs, for
example, metoprolol and propranolol, are generally metabolized
by the liver and have shorter half-lives than water-soluble drugs,
for example, atenolol, which are excreted largely unchanged in
the urine. An exception is esmolol, which is metabolized by
ester hydrolysis accounting for its rapid offset of action.
There is evidence that β-blockers have cardioprotective bene-
fits when used perioperatively. Patients taking β-blockers who
suffer myocardial infarction in the perioperative period are
more likely to survive than those who are not. Patients on estab-
lished β-blocker therapy are therefore recommended to continue
treatment through the perioperative period.9 Initiation of therapy
before operation is more controversial, particularly in patients
with low cardiovascular risk. The POISE study evaluated the
effect of commencing metoprolol at a fixed dose on the day of
surgery in patients with the risk of atherosclerotic disease under-
going non-cardiac surgery. While fewer patients in the metopro-
lol group suffered a myocardial infarction, their risks of stroke
and all-cause mortality were greater than the placebo group.10
There may, however, be a role for carefully titrated preoperative
β-blockers in planned procedures.
α-Blockers
α-Blockers are used to treat hypertension in patients resistant
to, or intolerant of, other treatments. Specific indications for
their use in secondary hypertension include labetalol for pre-
eclampsia and phentolamine in the perioperative management
of phaeochromocytoma. α-Blockers are also commonly used
to improve urinary flow in benign prostatic hyperplasia, for
example, tamsulosin.
Most α-blockers selectively target post-ganglionic α1 Gq
protein-coupled receptors leading to peripheral vasodilatation
and reduced SVR. Non-selective α-blockers, for example, phen-
tolamine and phenoxybenzamine, act at α1 and α2 receptors.
Blockade of presynaptic α2 Gi-protein-coupled receptors leads
BJA Education | Volume 15, Number 6, 2015 283
Antihypertensive drugs
to norepinephrine release with resultant tachycardia and in-
creased cardiac output.
Labetalol is a non-selective β-blocker which also acts as an α1
adrenoceptor blocker. Therefore, it manipulates arterial pressure
by acting upon multiple pathways. Adverse effects of α-block
include orthostatic hypotension with a reflex tachycardic re-
sponse, especially after a first dose. In patients unable to mount
a tachycardic response, for instance, those taking rate-limiting
drugs, this can lead to profound hypotension and syncope.
Other side-effects include oedema, headache, incontinence,
and drowsiness.
Calcium channel blockers
CCBs are first-line treatment for primary hypertension in
patients over the age of 55 and black patients of African or
Caribbean family origin. Rate-controlling CCBs (diltiazem, verap-
amil) are also used to manage tachyarrhythmias and angina,
where their negative inotropic and chronotropic effects improve
the myocardial oxygen supply:demand ratio. Some CCBs have
specific non-cardiac indications, for example, nimodipine in
neurosurgery to reduce cerebral vasospasm in patients after
spontaneous subarachnoid haemorrhage, and verapamil in
neurology to treat cluster headache.
CCBs act on -type calcium channels present in vascular
smooth muscle and in myocardial and nodal tissues. The vari-
able affinity of the different CCBs to these different tissues deter-
mines their effects. Those with higher affinity to cardiac tissue
(diltiazem, verapamil) cause negative chronotropy and inotropy.
Those with higher affinity to vascular smooth muscle cause
peripheral vasodilatation and reduced SVR, which may result in
reflex cardiac stimulation.
Cardiovascular side-effects include reflex tachycardia which
may potentiate myocardial ischaemia, disturbance of the periph-
eral microcirculation leading to swelling of the hands and feet,
flushing, and headache. Rate-limiting agents prolong atrio-
ventricular conduction and cause bradycardia; the negative
inotropic and chronotropic effects may worsen heart failure.
CCBs are a chemically diverse group of drugs, which comprise
phenylalkylamines, for example, verapamil; dihydropyridines,
for example, amlodipine and nifedipine; and benzothiazepines,
for example, diltiazem. CCBs have varying pharmacokinetic
properties. Most are orally administered, although their bioavail-
ability is generally low due to extensive first-pass metabolism. I.V.
preparations are available for some drugs (verapamil, nimodipine,
nicardipine), while nifedipine may be administered sublingually.
Most have half-lives of <12 h, although there are exceptions,
including amlodipine, which has a significantly longer half-life.
There is little evidence that commencing or continuing the
use of CCBs perioperatively reduces the risk of myocardial infarc-
tion or death. While there is evidence that continued use of CCBs
in the presence of β-blockers may lead to increased incidence of
hypotension under anaesthesia, it is not generally recommended
that CCBs be withheld before surgery.7
Diuretics
Thiazide (bendroflumethiazide, hydrochlorothiazide) and thia-
zide-like (chlortalidone, indapamide) diuretics are the most com-
monly prescribed diuretic agents used to treat hypertension.
They are used in patients intolerant of CCBs and in patients
with heart failure, or at risk of heart failure. They are also used
as ‘add on’ drugs in patients who have not responded to first-
and second-line antihypertensive treatments.1
284 BJA Education | Volume 15, Number 6, 2015
Thiazide diuretics act on the proximal part of the distal tubule
to inhibit sodium and chloride reabsorption, with resultant
reduction in water reabsorption leading to diuresis. The diuretic
effect is dependent upon their excretion into the renal tubule and
is therefore reduced in renal impairment.
Some of the antihypertensive effect of thiazides can be
attributed to their diuretic effect leading to a reduction in blood
volume. However, thiazides also cause vasodilatation and reduce
the responsiveness of vascular smooth muscle to vasoactive sub-
stances resulting in a reduction in SVR. One direct mechanism by
which thiazides cause these effects is through opening of cal-
cium-activated potassium channels.
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Thiazide diuretics have many clinically relevant biochemical
side-effects including hypokalaemia, hypercalcaemia, hypona-
traemia, hypomagnesaemia, hyperglycaemia, hyperuricaemia,
hypercholesterolaemia, and hypochloraemic alkalosis. Plasma
volume loss may precipitate dehydration and acute kidney injury.
Less common side-effects include skin rashes, photosensitivity
reactions, and blood dyscrasias including thrombocytopaenia.
Aldosterone antagonists, for example, spironolactone, are re-
commended as fourth-line treatment of primary hypertension.
The use of these drugs carries a risk of hyperkalaemia, particular-
ly in patients with impaired renal function or who are taking
other potassium-sparing agents. Loop diuretics are indicated
for resistant hypertension in patients with heart failure, chronic
kidney disease, and in those at risk of hyperkalaemia.
While diuretic therapy may be continued during the peri-
operative period, attention should be paid to the patient’s fluid
status and the potential for precipitating an acute kidney injury
and metabolic or electrolyte abnormalities.
Other antihypertensives
Vasodilators
Directly acting vasodilators, for example, hydralazine and
minoxidil, are seldom used due to their side-effect profiles.
Hydralazine is used in hypertension secondary to pre-eclampsia.
In addition to its antihypertensive effects, minoxidil is used top-
ically as a treatment for male pattern baldness.
Vasodilators cause relaxation of vascular smooth muscle in
resistance (arteriolar) vessels. Minoxidil achieves this via adeno-
sine triphosphate-dependent potassium channels on smooth
muscle cell membranes. Hydralazine acts through activation of
adenylate cyclase, increasing intracellular cyclic guanosine
monophosphate. Vasodilatation provokes reflex cardiac stimula-
tion (which may precipitate cardiac ischaemia) and RAS activa-
tion. These compensatory responses may be offset by β-blockers
or diuretics.
Vasodilator drugs are poorly tolerated. Side-effects include
headache, fluid retention, and oedema. Other specific side-
effects include left ventricular hypertrophy, pericardial and
pleural effusions, hypertrichosis and coarsening of features
with minoxidil, while peripheral neuropathy, blood dyscrasias,
and a lupus-like reaction can occur with hydralazine.
Centrally acting agents
Centrally acting agents include clonidine (α2 adrenoceptor agon-
ist), methyldopa ( precursor of an α2 adrenoceptor agonist), and
moxonidine (agonist at imidazoline binding sites). Their use in
primary hypertension is limited to difficult to treat cases, while
methyldopa is used to treat hypertension in pregnancy. The

evidence base for the use of centrally acting drugs in hyperten-
sion is limited and adverse effects are common.
Clonidine is an analgesic and sedative drug which reduces the
minimum alveolar concentration of inhalation anaesthetic
agents. Both of these drugs cause side-effects including dry
mouth and sedation. Methyldopa has immunological side-
effects, including pyrexia, haemolytic anaemia, and hepatitis.
Cessation of treatment with clonidine can cause rebound
hypertension.
Ganglion blockers
Ganglion blockers, such as trimetaphan, antagonize acetylcho-
line at nicotinic receptors, including those at the adrenal cortex.
Trimetaphan causes vasodilatation with a consequent rapid re-
duction in arterial pressure. Although ganglion blockers may be
used to manage hypertensive crises or to provide hypotensive
anaesthesia, their use is increasingly rare.
Declaration of interest
None declared.
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References
1. NICE Guideline 127. Hypertension: Clinical Management of
Hypertension in Adults. Manchester: National Institute for
Health and Clinical Excellence, 2011
Antihypertensive drugs
2. Therapeutics. British Hypertension Society. Available from
http://www.bhsoc.org/resources/therapeutics/ (accessed 1
September 2014)
3. Brown MJ. Aliskiren. Circulation 2008; 118: 773–84
4. Peck TE, Hill SA, Williams M. Antihypertensives. Pharmacology
for Anaesthesia and Intensive Care, 3rd Edn. Cambridge:
Cambridge University Press, 2008; 259–69
5. van Vark LC, Bertrand M, Akkerhuis KM et al. Angiotensin-
converting enzyme inhibitors reduce mortality in hyper-
tension: a meta-analysis of randomized clinical trials of
renin–angiotensin–aldosterone system inhibitors involving
158,998 patients. Eur Heart J 2012; 33: 2088–97
Downloaded from https://academic.oup.com/bjaed/article-abstract/15/6/280/356246 by guest on 27 September 2019
6. Rosenman DJ, McDonald FS, Ebbert JO et al. Clinical
consequences of withholding versus administering renin–
angiotensin–aldosterone system antagonists in the pre-
operative period. J Hosp Med 2008; 3: 319–25
7. Smith I, Jackson I. Beta-blockers, calcium channel blockers,
angiotensin converting enzyme inhibitors and angiotensin
receptor blockers: should they be stopped or not before
ambulatory anaesthesia? Curr Opin Anaesthesiol 2010; 23:
687–90
8. Auron M, Harte B, Kumar A et al. Renin–angiotensin system
antagonists in the perioperative setting: clinical conse-
quences and recommendations for practice. Postgrad Med J
2011; 87: 472–81
9. Fleisher LA, Beckman JA, Brown KA et al. 2009 ACCF/AHA
focused update on perioperative beta blockade incorporated
into the ACC/AHA 2007 guidelines on perioperative cardio-
vascular evaluation and care for noncardiac surgery. J Am
Coll Cardiol 2009; 54: e13–118
10. Devereaux PJ, Yang H, Yusuf S et al. Effects of extended-
release metoprolol succinate in patients undergoing non-
cardiac surgery (POISE trial): a randomised controlled trial.
Lancet 2008; 371: 1839–47
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