ACE Inhibitors

Class Summary

Angiotensin converting enzyme (ACE) inhibitors are the treatment of choice in patients with
hypertension, chronic kidney disease, and proteinuria. ACE inhibitors reduce morbidity and mortality
rates in patients with heart failure, patients with recent myocardial infarctions, and patients with
proteinuric renal disease. ACE inhibitors appear to act primarily through suppression of the renin-
angiotensin-aldosterone system. ACE inhibitors prevent the conversion of angiotensin I to
angiotensin II and block the major pathway of bradykinin degradation by inhibiting ACE.
Accumulation of bradykinin has been proposed as an etiologic mechanism for the side effects of
cough and angioedema. ACE inhibitors can cause injury or even death to a developing fetus. In
pregnant patients, ACE inhibitors should be discontinued as soon as possible.

It is important to note that the blood-pressure-lowering effects of ACE inhibitors and thiazides are
approximately additive, and there is also the potential for hyperkalemia when ACE inhibitors are
coadministered with potassium supplements or potassium-sparing diuretics. In addition, a study by
Harel et al found an increased risk for hyperkalemia when aliskiren, a direct renin inhibitor, and ACE
inhibitors or angiotensin receptor blockers were used together. [125] Careful monitoring of serum
potassium levels is warranted when these agents are used in combination. [125] Furthermore, in
patients with hypertension plus type 2 diabetes and renal impairment who are at high risk of
cardiovascular and renal events, there is an increased risk of nonfatal stroke, renal complications,
hypokalemia, and hypotension when aliskiren is added to ACE inhibitor or ARB therapy.

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 recommended for patients with reduced left ventricular systolic function
(including those who are asymptomatic), usually combined with a beta-blocker (section 2.5.5).
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 may
be beneficial in severe heart failure (section 2.5.5) 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 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, see below. 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. In heart failure the dose of an ACE inhibitor should be
gradually titrated to the target dose or highest tolerated dose. See individual drug monographs and
also SafeRxGuide for initiation and up-titration of ACE inhibitors in patients with heart failure.

Hypertension

An ACE inhibitor may be the most appropriate initial drug for hypertension in younger patients;
those aged over 55 years, and those with primary aldosteronism respond less well (see section 2.5).
ACE inhibitors are particularly indicated for hypertension in patients with diabetes with nephropathy
(see also section 6.1.5). They may reduce blood pressure very rapidly in some patients particularly in
those receiving diuretic therapy (see Cautions, below); the first dose should preferably be given at
bedtime.

Diabetic nephropathy

For comment on the role of ACE inhibitors in the management of diabetic nephropathy,

Fosinopril

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Fosinopril may be used alone or in combination with other antihypertensive agents. Initial dose is 5
mg daily up to a maximum of 40 mg daily. May be divided into twice daily dosing. Unlike most ACE
inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated by both renal and
hepatic pathways, making it a safer choice in patients with renal failure and heart failure patients
with impaired kidney function.

Captopril
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Captopril is indicated for the treatment of hypertension. It can be used alone or in combination with
other antihypertensive drugs, such as diuretics or beta-adrenergic-blocking agents. The initial dose is
25 mg given 2 to 3 times daily. If reduction of blood pressure is not achieved after 1 or 2 weeks, the
dose can be titrated to 50 mg 2 or 3 times daily. If further blood reduction is required after addition
of a diuretic, the dose of captopril may be increased to 100 mg 2 or 3 times daily and then, if
necessary, to 150 mg 2 or 3 times daily (while continuing the diuretic).

captopril

Indications hypertension; heart failure (see section 2.5.5); following myocardial infarction in
clinically stable patients (see section 2.10.1); diabetic nephropathy in type 1 diabetes; diabetic
nephropathy in type 2 diabetes [unapproved]

Contra-indications hypersensitivity to ACE inhibitors (including angioedema); pregnancy

Anaphylactoid reactions

To prevent anaphylactoid reactions, ACE inhibitors should be avoided during dialysis with high-flux
polyacrylonitrile membranes and during low-density lipoprotein apheresis with dextran sulphate;
they should also be withheld before desensitisation with wasp or bee venom.

Cautions patients already taking diuretics (see Concomitant diuretics below); first doses can cause
hypotension (particularly if on high doses of diuretics, low-sodium diet, dialysis, dehydrated, or with
heart failure); peripheral vascular disease or generalised atherosclerosis owing to risk of clinically
silent renovascular disease; for use in pre-existing renovascular disease, see Renal effects; renal
function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose)
and monitored during treatment; collagen vascular disease (increased risk of agranulocytosisblood
counts recommended); severe or symptomatic aortic stenosis (risk of hypotension); hypertrophic
cardiomyopathy; concomitant medication or supplements that increase serum potassium
concentration; concomitant NSAIDs (increased risk of renal damage); idiopathic or hereditary
angioedema; discontinue if jaundice or marked elevation of hepatic enzymesrisk of hepatic
necrosis

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 failurerisk 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.

Interactions Stockley's alerts: captopril; BNF summary: captopril

Renal impairment

see notes; reduce dose; maximum initial dose 50 mg if eGFR above 40 mL/minute/1.73m 2; maximum
initial dose 25 mg daily (do not exceed100 mg daily) if eGFR 2040 mL/minute/1.73 m2; maximum
initial dose 12.5 mg daily (do not exceed 75 mg daily) if eGFR 1020 mL/minute/1.73 m2; maximum
initial dose6.25 mg daily (do not exceed 37.5 mg daily) if eGFR less than 10 mL/minute/1.73 m2

Pregnancy D ; ACE inhibitors should be avoided at all stages of pregnancy. Fetal skull defects have
been reported following first trimester exposure to ACE inhibitors although evidence of
teratogenicity of is inconclusive. In the second and third trimesters ACE inhibitors can cause
abnormalities including fetal growth retardation, oligohydramnios and fetal/neonatal renal failure.
Fetal death in utero has also been reported. Pregnant women who are taking ACE inhibitors should
be changed to an alternative antihypertensive as soon as possible

Breast-feeding compatible eTG complete

Adverse effects

gastro-intestinal disturbance (including nausea, vomiting, dyspepsia, diarrhoea, constipation,

abdominal pain), dry mouth, hypotension, dyspnoea, persistent dry cough, sleep disorder, renal
impairment, hyperkalaemia, alopecia; less commonly elevated liver function tests (see Cautions),
angioedema (onset may be delayed, higher incidence in Afro-Caribbean patients), tachycardia,
palpitation, arrhythmia, angina, pallor, flushing, Raynauds syndrome, upper respiratory-tract
symptoms (including sinusitis, rhinitis, sore throat), rash (may be associated with pruritus and
urticaria); rarely stomatitis, anorexia; very rarely glossitis, peptic ulcer, hepatitis, cholestatic
jaundice, fulminant hepatic necrosis, hepatic failure, pancreatitis, syncope, cerebrovascular events,
cardiac arrest, cardiogenic shock, allergic alveolitis, eosinophilic pneumonia, confusion, depression,
impotence, gynaecomastia, hyponatraemia, hypoglycaemia, thrombocytopenia, leucopenia,
neutropenia, haemolytic anaemia, blurred vision, photosensitivity, Stevens-Johnson syndrome; also
reported headache, dizziness, fatigue, malaise, taste disturbance, paraesthesia, bronchospasm,
fever, serositis, vasculitis, myalgia, arthralgia, interstitial nephritis, positive antinuclear antibody,
raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, photosensitivity

Dose
Hypertension

Oral

Adult initially 12.525 mg twice daily; maximum 150 mg daily in 2 divided

doses; elderly initially 6.25 mg twice daily; in volume depletion (see Concomitant diuretics above),
cardiac decompensation, or renovascular hypertension, initially 6.2512.5 mg as a single dose
preferably under close medical supervision, then twice daily; increased if necessary at intervals of at
least 2 weeks up to maximum 150 mg daily in 2 divided doses (maximum 100 mg daily in 12 divided
doses in volume depletion, cardiac decompensation, or renovascular hypertension); once-daily
dosing may be appropriate if other concomitant antihypertensive drugs taken

Heart failure

Oral

Adult initially 6.2512.5 mg 23 times daily under close medical supervision (see notes), increased
gradually at intervals of at least 2 weeks up to a target dose of 50 mg 3 times daily, if tolerated:
maximum 150 mg daily

Note

Aim for the target dose or highest tolerated dose; the dose can be approximately doubled every 2
weeks if tolerated; check blood pressure, serum potassium and renal function prior to each dose
increase.

Following myocardial infarction in clinically stable patients

Oral

Adult initially 6.25 mg once daily, then 12.5 mg 3 times daily, increasing over several days as
tolerated; doses exceeding 75 mg daily to be increased more gradually; maximum 150 mg daily in 2
3 divided doses

Diabetic nephropathy in type 1 diabetes; diabetic nephropathy in type 2 diabetes [unapproved

indication]

Oral

Adult 2550 mg 23 times daily, monitor blood pressure closely, titrate to maximum tolerated dose;
usual maximum 150 mg daily in divided doses

Patient advice

Take 1 hour before meals.

Ramipril (Altace)
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Ramipril is indicated for the treatment of hypertension alone or in combination with thiazide
diuretics. The initial dosing recommendation for ramipril is 2.5 mg daily for patients who are not
receiving a diuretic. Doses can range from 2.5-20 mg/day given once or twice a day.

Enalapril (Vasotec)

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Enalapril is effective alone or in combination with other antihypertensive agents, especially thiazide-
type diuretics. The initial dose of enalapril is 5 mg daily. Dosage can range from 10-40 mg/day
administered as a single dose or in 2 divided doses.

Lisinopril (Prinivil, Zestril)

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Lisinopril may be used as monotherapy or concomitantly with other classes of antihypertensive

agents. The initial dose of lisinopril is 10 mg daily. The dosage can range from 20-40 mg/day as a
single daily dose. Doses up to 80 mg/day have been used; however, they do not show a greater
effect.

Quinapril (Accupril)

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Quinapril may be used alone or in combination with thiazide diuretics. The initial dose is 10 to 20 mg
daily for patients not on diuretics. If blood pressure is not controlled with quinapril monotherapy,
adding a diuretic should be considered.

Calcium-channel blockers (CCBs) - blood pressure

medication
Calcium-channel blockers (CCBs for short) are medicines that are often used to treat high blood
pressure. There are a few different types of CCB and each works in a slightly different way. Most of
these medicines will have names that end in ipine.

Your body will sometimes use calcium to narrow your blood vessels and this can raise your blood
pressure. Calcium-channel blockers (CCBs) lower your blood pressure by blocking the effects of
calcium on your blood vessels. This helps your blood vessel walls relax and widen, making it easier
for blood to flow through.

Dihydropyridines Type:-

Amiodipine

Felodipine

Lercanidipine

Nifedipine

Non-dihydropyridines Type: -

Deltiazem
Verapamil

Calcium channel blockers (CCBs) can be divided into dihydropyridines and nondihydropyridines.
Dihydropyridines bind to L-type calcium channels in the vascular smooth muscle, which results in
vasodilatation and a decrease in blood pressure. They are effective as monotherapy in black patients
and elderly patients. Some examples of dihydropyridines include amlodipine, nifedipine, clevidipine,
and felodipine. Non-dihydropyridines such as verapamil and diltiazem bind to L-type calcium
channels in the sinoatrial and atrioventricular node, as well as exerting effects in the myocardium
and vasculature. These agents may constitute a more effective class of medication for black patients.

Beta-Adrenoceptor Antagonists (Beta-Blockers)

General Pharmacology

Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding
of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic effects that
act through these receptors. Therefore, beta-blockers are sympatholytic drugs. Some beta-blockers,
when they bind to the beta-adrenoceptor, partially activate the receptor while preventing
norepinephrine from binding to the receptor. These partial agonists therefore provide some
"background" of sympathetic activity while preventing normal and enhanced sympathetic activity.
These particular beta-blockers (partial agonists) are said to possess intrinsic sympathomimetic
activity (ISA). Some beta-blockers also possess what is referred to as membrane stabilizing activity
(MSA). This effect is similar to the membrane stabilizing activity of sodium-channels blockers that
represent Class I antiarrhythmics.

The first generation of beta-blockers were non-selective, meaning that they blocked both beta-1 (1)
and beta-1 (2) adrenoceptors. Second generation beta-blockers are more cardioselective in that
they are relatively selective for 1 adrenoceptors. Note that this relative selectivity can be lost at
higher drug doses. Finally, the third generation beta-blockers are drugs that also possess vasodilator
actions through blockade of vascular alpha-adrenoceptors.
Heart

Beta-blockers bind to beta-adrenoceptors located in cardiac nodal tissue, the conducting system,
and contracting myocytes. The heart has both 1 and 2adrenoceptors, although the predominant
receptor type in number and function is 1. These receptors primarily bind norepinephrine that is
released from sympathetic adrenergic nerves. Additionally, they bind norepinephrine and
epinephrine that circulate in the blood. Beta-blockers prevent the normal ligand (norepinephrine or
epinephrine) from binding to the beta-adrenoceptor by competing for the binding site.

Beta-adrenoceptors are coupled to a Gs-proteins, which activate adenylyl cyclase to

form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that
phosphorylates L-type calcium channels, which causes increased calcium entry into the cell.
Increased calcium entry during action potentials leads to enhanced release of calcium by the
sarcoplasmic reticulum in the heart; these actions increase inotropy (contractility). Gs-protein
activation also increases heart rate (chronotropy). PK-A also phosphorylates sites on the
sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine receptors
(ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic reticulum. This
provides more calcium for binding the troponin-C, which enhances inotropy. Finally, PK-A can
phosphorylate myosin light chains, which may contribute to the positive inotropic effect of beta-
adrenoceptor stimulation.

Because there is generally some level of sympathetic tone on the heart, beta-blockers are able to
reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy
(contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-
blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate. These
drugs have an even greater effect when there is elevated sympathetic activity.

Blood vessels

Vascular smooth muscle has 2-adrenoceptors that are normally activated by norepinephrine
released by sympathetic adrenergic nerves or by circulating epinephrine. These receptors, like those
in the heart, are coupled to a Gs-protein, which stimulates the formation of cAMP. Although
increased cAMP enhances cardiac myocyte contraction (see above), in vascular smooth muscle an
increase in cAMP leads to smooth muscle relaxation. The reason for this is that cAMP inhibits myosin
light chain kinase that is responsible for phosphorylating smooth muscle myosin. Therefore,
increases in intracellular cAMP caused by 2-agonists inhibits myosin light chain kinase thereby
producing less contractile force (i.e., promoting relaxation).

Compared to their effects in the heart, beta-blockers have relatively little vascular effect because 2-
adrenoceptors have only a small modulatory role on basal vascular tone. Nevertheless, blockade of
2-adrenoceptors is associated with a small degree of vasoconstriction in many vascular beds. This
occurs because beta-blockers remove a small 2-adrenoceptor vasodilator influence that is normally
opposing the more dominant alpha-adrenoceptor mediated vasoconstrictor influence.

Therapeutic Indications

Beta-Blockers

Cardiac Effects

Decrease contractility
(negative intropy)

Decrease relaxation rate

(negative lusitropy)

Decrease heart rate

(negative chronotropy)

Decrease conduction velocity

(negative dromotropy)

Vascular Effects

Smooth muscle contraction

(mild vasoconstriction)

Beta-blockers are used for treating hypertension, angina, myocardial infarction, arrhythmias and
heart failure.

Hypertension

Clinical Uses

Class/Drug HTN Angina Arrhy MI CHF Comments

Non-selective
1/2

carteolol X ISA; long acting; also used for glaucoma

carvedilol X X -blocking activity

labetalol X X ISA; -blocking activity

nadolol X X X X long acting

 penbutolol X X ISA

pindolol X X ISA; MSA

propranolol X X X X MSA; prototypical beta-blocker

sotalol X several other significant mechanisms

timolol X X X X primarily used for glaucoma

1-selective

acebutolol X X X ISA

atenolol X X X X

betaxolol X X X MSA

bisoprolol X X X X

esmolol X X ultra short acting; intra or postoperative HTN

metoprolol X X X X X MSA

relatively selective in most patients;

nebivolol X
vasodilating (NO release)

Diuretics
Mechanism of action. Loop diuretics act on the Na+-K+-2Cl symporter (cotransporter) in the thick
ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption. ... Loop
diuretics cause a decrease in the renal blood flow by this mechanism.

Thiazides and related diuretics

Loop diuretics

Potassium-sparing diuretics and aldosterone antagonists :Amiloride is a weak diuretic. It causes

retention of potassium and is therefore given with thiazide or loop diuretics as a more effective
alternative to potassium supplements

Loop diuretics are used in pulmonary oedema due to left ventricular failure; intravenous
administration produces relief of breathlessness and reduces pre-load sooner than would be
expected from the time of onset of diuresis. Loop diuretics are also used in patients with chronic
heart failure. Diuretic-resistant oedema (except lymphoedema and oedema due to peripheral
venous stasis or calcium-channel blockers) can be treated with a loop diuretic combined with a
thiazide or related diuretic (e.g. bendroflumethiazide 510 mg daily or metolazone 2.520 mg daily
[section 29, unapproved medicine].

If necessary, a loop diuretic can be added to antihypertensive treatment to achieve better control of
blood pressure in those with resistant hypertension, or in patients with impaired renal function or
heart failure.

Loop diuretics inhibit reabsorption from the ascending limb of the loop of Henl in the renal tubule
and are powerful diuretics.

Furosemide and bumetanide have similar activity; both act within 1 hour of oral administration and
diuresis is complete within 6 hours so that, if necessary, they can be given twice in one day without
interfering with sleep. Following intravenous administration furosemide has a peak effect within 30
minutes. The diuresis associated with loop diuretics is dose related.

Cautions

Hypovolaemia and hypotension should be corrected before initiation of treatment with loop
diuretics; electrolytes should be monitored during treatment (see also Potassium Loss, section 2.2).
Loop diuretics can exacerbate diabetes (but hyperglycaemia is less likely than with thiazides) and
gout. If there is an enlarged prostate, urinary retention can occur, although this is less likely if small
doses and less potent diuretics are used initially; an adequate urinary output should be established
before initiating treatment; BNF summary: Loop diuretics.

Contra-indications

Loop diuretics should be avoided in severe hypokalaemia, severe hyponatraemia, anuria, comatose
and precomatose states associated with liver cirrhosis, and in renal failure due to nephrotoxic or
hepatotoxic drugs.

Hepatic impairment

Hypokalaemia induced by loop diuretics may precipitate hepatic encephalopathy and coma
potassium-sparing diuretics can be used to prevent this.

Renal impairment

High doses of loop diuretics may occasionally be needed; high doses or rapid intravenous
administration can cause tinnitus and deafness; high doses of bumetanide can also cause
musculoskeletal pain.

Pregnancy

Furosemide and bumetanide should not be used to treat gestational hypertension because of the
maternal hypovolaemia associated with this condition.

Adverse effects

Adverse effects of loop diuretics include mild gastro-intestinal disturbances, pancreatitis, hepatic
encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride
concentration, hyperglycaemia (less common than with thiazides), acute urinary retention,
electrolyte disturbances (including hyponatraemia, hypokalaemia (see section 2.2), hypocalcaemia,
hypochloraemia, and hypomagnesaemia), metabolic alkalosis, blood disorders (including bone-
marrow depression, thrombocytopenia, and leucopenia), hyperuricaemia, visual disturbances,
tinnitus and deafness (usually with high parenteral doses and rapid administration, and in renal
impairment), and hypersensitivity reactions (including rash, photosensitivity, and pruritus).

bumetanide

furosemide

thiazides and related compounds are moderately potent diuretics; they inhibit sodium reabsorption
at the beginning of the distal convoluted tubule. They act within 1 to 2 hours of oral administration
and most have a duration of action of 12 to 24 hours; they are usually administered early in the day
so that the diuresis does not interfere with sleep.

In the management of hypertension, as a cardiovascular risk factor, a low dose of a thiazide produces
a maximal or near-maximal blood pressure lowering effect, with very little biochemical disturbance.
Higher doses cause more marked changes in plasma potassium, sodium, uric acid, glucose, and
lipids, with little advantage in blood pressure control. For reference to the use of thiazides in chronic
heart failure

Bendroflumethiazide (bendrofluazide)

Chlortalidone,

Metolazone

Hydrochlorothiazide

http://blausen.com/en/video/alpha-adrenergic-blockers/

Alpha 1 -Adrenergic Blocker

Definition

Alpha1-adrenergic blockers are drugs that work by blocking the alpha1-

receptors of vascular smoothmuscle, thus preventing the uptake of catecholamines by the smooth m
uscle cells. This causesvasodilation and allows blood to flow more easily.

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 and terazosin have properties similar to those of prazosin.

Alpha-blockers can be used with other antihypertensive drugs in the treatment of resistant
hypertension

http://blausen.com/en/video/alpha-adrenergic-blockers/

Angiotensin-II receptor antagonists

Angiotensin II receptor blockers (ARBs) are medications that block the action ofangiotensin II by
preventing angiotensin II from binding to angiotensin II receptors on the muscles surrounding blood vessels.
As a result, blood vessels enlarge (dilate) and blood pressure is reduced

Candesartan and losartan, 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 (section 2.5.5) or diabetic nephropathy (section 6.1.5).

Cautions

Angiotensin-II receptor antagonists should be initiated with care in patients who are volume or
sodium depleted e.g. from diuretics (especially with higher doses of a loop diuretic), dietary salt
restriction, vomiting or diarrhoea. Where possible correct volume and sodium depletion before
starting an angiotensin-II receptor antagonist or consider initiating treatment at a lower dose, and
monitor blood pressure.

Angiotensin-II receptor antagonists should be used with caution in renal artery stenosis (see also
Renal Effects under ACE Inhibitors, section 2.5.5.1). Monitoring of plasma-potassium concentration
is advised, particularly in the elderly and in patients with renal impairment; lower initial doses may
be appropriate in these patients. Angiotensin-II receptor antagonists should be used with caution in
aortic or mitral valve stenosis and in hypertrophic cardiomyopathy. Those with primary
aldosteronism, (particularly those with left ventricular hypertrophy), may not benefit from an
angiotensin-II receptor antagonist