Pharmacology of

Antihypertensive ACEIs & ARBs

DR KAYATRI GOVINDARAJU
 Hypertension
▪ Pre-hypertension is when systolic blood pressure is between 120 and 129
mmHg and less than 80 mmHg on the diastolic side.

▪ Stage 1 hypertension is between 130 and 139 mmHg on the systolic side,
and between 80 and 89 mmHg on the diastolic side.

▪ Stage 2 hypertension is defined as anything that is 140 mmHg or higher on

the systolic side and 90 mmHg or higher on the diastolic side.

▪ First step for an office blood pressure, is to make sure that the patient has
rested for at least five minutes and is positioned properly - sitting with their
arms and back supported, and their feet flat on the floor. And the
measurement should be repeated at least twice. Most of the time, blood
pressure is taken in the brachial artery in the upper arm, because if the
pressure is high there, it’s probably high throughout the arteries. The diagnosis
of hypertension should be done by looking at both office and out-of-office
blood pressure measurements.

There are two main types of hypertension - primary or essential hypertension has no clearly identifiable underlying reason,
and secondary hypertension, which does have a specific, identifiable underlying condition
 Types of hypertension

Primary hypertension is way more common, and

it generally isn’t accompanied by symptoms. It’s Risk factors for primary hypertension include: old age, obesity,
sometimes called a “silent killer”, because over family history, a salt-heavy diet, a sedentary lifestyle, heavy
alcohol consumption, smoking, and race - for example, people
time, pressure in the arteries silently creeps up, of African descent are more likely to develop hypertension. And
and causes blood vessel damage which is a risk some of these risk factors can be improved with lifestyle changes
factor for serious problems, like myocardial that can help reduce hypertension.
infarctions, aneurysms, and strokes.

Anything that limits the renal blood flow can cause

Secondary hypertension often is accompanied by a hypertension, e.g fibromuscular dysplasia, which generally
affects young women, but also atherosclerosis in older patients.
variety of symptoms associated with the underlying Other examples include obstructive sleep apnea,
cause. In general, the younger the patient, the more atherosclerosis, vasculitis, or aortic dissection, as well as
likely it’s secondary hypertension. pheochromocytoma, Cushing’s syndrome, and other
endocrine disorders.
It’s also important to identify signs of end-organ damage, and whether the patient takes any
medications or exogenous substances that can worsen hypertension, sympathomimetic
agents like decongestants or even cocaine, cyclosporine or tacrolimus, sodium-containing
antacids, stimulants like amphetamines, atypical antipsychotics like clozapine,
antidepressants, oral contraceptives, erythropoietin, and even NSAIDS and liquorice
Pathology
Pathology
Pathology
What happens to the heart
What happens to the brain and kidney
 Mechanisms for controlling blood
pressure

▪ Arterial blood pressure is directly proportional to cardiac output

and peripheral vascular resistance

▪ Cardiac output and peripheral resistance, in turn, are controlled

mainly by two overlapping control mechanisms: the baroreflexes
and the renin-angiotensin–aldosterone system

▪ Baroreflexes act by changing the activity of the sympathetic nervous

system. A fall in blood pressure causes pressure-sensitive neurons
(baroreceptors in the aortic arch and carotid sinuses) to send fewer
impulses to cardiovascular centres in the spinal cord.

▪ RAAS: The kidney provides long-term control of blood pressure by

altering the blood volume. Baroreceptors in the kidney respond to
reduced arterial pressure (and to sympathetic stimulation of β1 -
adrenoceptors) by releasing the enzyme renin. Low sodium intake and
greater sodium loss also increase renin release. Renin converts
angiotensinogen to angiotensin I, which is converted in turn to
angiotensin II, in the presence of angiotensin-converting enzyme (ACE).
▪ Lifestyle changes are crucial for all patients, especially in the long term,
and include things like quitting smoking, drinking alcohol in
moderation, maintaining a healthy weight, reducing dietary sodium,
So how do we manage it?
and staying physically active.

▪ These dietary guidelines promote the consumption of fruits, vegetables, ▪ Management for hypertension is mainly based on the
grains, dairy products, and food rich in K+, Mg+2, Ca+2, and phosphorus. hypertension stage, risk of developing cardiovascular
Restriction of Na+ intake has the greatest role in lowering the blood events and organ damage, as well as taking into account
pressure (Consume less than 2.4 g of sodium per day) any concomitant diseases, such as diabetes or chronic
kidney disease.

▪ Maintain a normal body weight (i.e., body mass index less than
25 kg per m2). ▪ Not all patients with hypertension need antihypertensive drug
therapy.

▪ Get 30 minutes of aerobic activity at least four days per week.

▪ Proper management of hypertension may require both
pharmacological and non-pharmacological interventions.
▪ Smoking cessation should be part of any comprehensive
lifestyle modification plan to reduce the risk of high blood
pressure and cardiovascular disease.
▪ There are four main classes of medications that are used to treat
hypertension, ACE inhibitors, Angiotensin Receptor Blockers or
ARBs, thiazide diuretics, and long-acting calcium channel
blockers. There is a lot of variability in terms of how individuals
respond to different medications, so it’s important to follow up to
see how the medications are working.
 Antihypertensive therapy

▪ Antihypertensive drug treatment is mainly offered to the following:

➢ people aged under 80 years with stage 1

hypertension who have one or more of the
conditions like target organ damage,
established CVD, renal disease, diabetes, and a
10-year cardiovascular risk equivalent to 20% or
greater.

➢ people of any age with stage 2 hypertension

➢ people under 40 years with stage 1

hypertension and no evidence of target
organ damage, cardiovascular disease,
renal disease or diabetes
Antihypertensive therapy guideline
RAAS
 Direct renin inhibitors: Aliskiren

▪ It was developed by Speedel and Novartis and initially approved by the

FDA in early 2007.

▪ MOA: Aliskiren is a renin inhibitor. Renin is secreted by the kidneys

when blood volume and renal perfusion decrease. Aliskiren works via
binding to renin at its active site, stopping the cleavage of angiotensin, in
turn inhibiting the formation of angiotensin I. This ends the cascade of
angiotensin II-mediated mechanisms that normally increase blood
pressure.

▪ Combination therapy with two drugs affecting the renin-angiotensin system

(ACE inhibitors, angiotensin-II receptor antagonists, and aliskiren) is NOT
recommended due to an increased risk of hyperkalaemia, hypotension, and renal
impairment, compared to use of a single drug.
 ACEIs

▪ ACE inhibitors used as a first-line therapy for uncomplicated hypertension and are included in all first-line regimens for patients with
compelling indications

▪ ACE inhibitor may be the most appropriate initial drug for hypertension in younger Caucasian patients; those aged over 55 years and those with
primary aldosteronism respond less well.

▪ These medications most commonly end with the suffix '-pril.' Examples include lisinopril, ramipril, and captopril, perindopril.

▪ MOA: ACE inhibitors are competitive inhibitors of ACE, which prevent the conversion of angiotensin I to angiotensin II. Angiotensin II
acts as a potent vasoconstrictor that, when inhibited, can reduce blood pressure by dilating vessels and decreasing aldosterone
secretion.

▪ ACE inhibitors are most commonly administered as oral agents, but intravenous forms are available.

▪ 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.
 ACEIs

▪ For hypertension the first dose should preferably be given at bedtime.

▪ Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during
treatment

▪ 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

▪ Common or very common side effects: cough, alopecia, angina pectoris, angioedema (may be delayed; more common in
Afro-Caribbean patients), arrhythmias, asthenia, chest pain, diarrhoea, dizziness, drowsiness, dry mouth

ACE inhibitors should be avoided in pregnancy unless essential. They

may adversely affect fetal and neonatal blood pressure control and renal
function
 ACEIs

Most common side effect of ACE inhibitors is dry cough... Other side effects include
hypotension, but it only
happens when the person
starts taking the medication,
when a person takes then eventually disappears.
ACE inhibitor,
bradykinins accumulate,
ACE breaks down and they’re thought to
bradykinin induce the cough reflex.

people using ACE

inhibitors should avoid a high
potassium diet because there’s
Bradykinin accumulation decreased aldosterone
also cause angioedema production, which means there’s
(painful swelling in the less potassium excretion in the
airways that is life- urine, and this could lead
threatening). to hyperkalemia.
 Angiotensin II receptor blockers (ARBs)

▪ ARBs are first-line options for treatment of uncomplicated hypertension and are a reasonable alternative to ACE
inhibitor

▪ MOA: The ARBs blunt the effects of angiotensin II via direct blockade of the angiotensin II type 1 receptor;
they have no effect on the generation of angiotensin II or breakdown of bradykinin or substance P. They are
therefore a useful alternative for patients who have to discontinue an ACE inhibitor because of persistent
cough

▪ Most ARBs are indicated for once-daily dosing, but at low doses, they may lose efficacy at the end of a dose
interval, thereby necessitating twice-daily dosing.

▪ ARBs is their drug names usually end with the suffix “sartan”.

▪ Example: Azilsartan, candesartan, irbesartan, olmesartan, losartan, valsartan, telmisartan, eprosartan

▪ The combination of an angiotensin-II receptor antagonist with aliskiren is contra-indictated in patients with
diabetes mellitus and renal impairment
Angiotensin II receptor blockers (ARBs)
Angiotensin II receptor blockers (ARBs)

ARBs should be avoided in pregnancy unless

essential. They may adversely affect fetal and
neonatal blood pressure control and renal function

Advise patients taking

NSAIDs that while they are
taking an ARB can reduce the
antihypertensive effect of
their medication.
1. ACE inhibitors have clinically significant interactions with:

A. Diclofenac
B. Digoxin
C. Lithium
D. Erythromycin
E. Carbimazole

2. Kelly is now 2 weeks’ pregnant. Which of the following antihypertensive drug classes is absolutely contraindicated in this woman?

A. Potassium channel openers

B. Angiotensin-converting enzyme (ACE) inhibitors
C. Ca2+ channel blockers
D. Alpha-1 blockers
E. Central sympatholytics

3. Mr Jones complained to his physician of a dry, disturbing cough. In addition, he noted that food seems to have lost its flavour. He was
recently diagnosed with stage 2 essential hypertension and had started a multidrug treatment 1 week earlier. Which of the following drugs
most likely caused the patient’s signs and symptoms?

A. Nifedipine
B. Clonidine
C. Propranolol
D. Minoxidil
E. Captopril
4. You’re teaching a patient about how angiotensin II receptor blockers (ARBs) work. Which statement below BEST describes how these
medications work on the body?*

A. “They prevent Angiotensin II Type I Receptors from binding with Angiotensin II.”
B. “These medications prevent the activation of Angiotensin II Type II Receptors from binding with Angiotensin II.”
C. “They inhibit angiotensin-converting-enzyme (ACE) from converting an Angiotensin I to Angiotensin II.”
D. “These medications prevent Angiotensin II Type I Receptors from binding with angiotensin-converting-enzyme (ACE).”

5. A patient who developed a dry, persistent cough while taking an ACE Inhibitor is switched to an angiotensin II receptor blocker (ARB). The
patient reports the cough is now gone but asks you to explain how this medication helped alleviate the cough. What is the correct response?

A. “ARBs prevent ACE (angiotensin-converting-enzyme) from breaking down bradykinin so a dry, persistent cough is less likely.”
B. “ARBs increase ACE (angiotensin-converting-enzyme) which helps decrease bradykinin levels and helps alleviate the cough.”
C. “ARBs do not inhibit ACE (angiotensin-converting-enzyme), which is a substance that inactivates bradykinin by breaking it down; therefore, a
cough is not likely with this medication.”
D. “ARBs prevent Angiotensin II Type I receptor sites from activating bradykinin in the lungs.”
Thank you!