CLINICAL PHARMACOLOGY OF HYPERTENSION

ROLE OF DRUGS THAT AFFECT

RENIN ANGIOTENSIN SYSTEM

NUR FADZLINA BINTI ZABRI

08201310006

Drugs affecting renin angiotensin system

ACE inhibitor
Angiotensin II
receptor antagonist
Direct renin inhibitor

Angiotensin converting enzyme inhibitors

Used as first line antihypertensive
drugs
Captopril
Perindopri
l

Enalapril
Ramipril

Lisinopril
Benazepril

 Mechanism of action
I. Inhibit generation of angiotensin ll
II. Inhibit degradation of bradykinin
III. Stimulate synthesis of vasodilating
prostaglandin through bradykinin

Pharmacokinetic
Administration : Given orally
IV in emergency
Food reduces absorption
Poorly cross blood-brain barrier (BBB)
Metabolized in liver
Excreted in urine

Features of ACE inhibitors

Drug

Captopri
l

Enalapril Lisinopri Perindop Ramipril

l
ril

Active/
prodrug

Active

Prodrug

Active

Absorption

Wellabsorbed,
decrease
with food

Rapidly
absorbed.
Undergoes
extensive
first pass
metabolis
m. Food
does not
reduce
absorption

Slowly and Poorly

incomplete absorbed.
ly
absorbed.
Food does
not affect
Food does absorption
not affect
absorption

Rapidly
absorped

24 hours

>24 hours

> 24 hours

Duration of 8-12 hours

action

Prodrug

>24 hours

Prodrug

Adverse effect

Cough
Angioedema
Proteinuria
Teratogenic effect
Severe hypotension
Neutropenia
Rashes
Itching
Loss of taste sensation

Contraindication
Bilateral renal
artery stenosis
Patient with
single kidney with
renal stenosis

Drug interaction
Potassium-sparing diuretics
Simultaneous administration leads to
hyperkalemia

Lithium
ACE inhibitor retards renal elimination of lithium
and potentiate its toxicity

NSAIDs
NSAIDs inhibit PG synthesis, promote Na+ and
water retention
Decrease antihypertensive effect on ACE
inhibitors

Therapeutic use

Hypertension
Congestive cardiac failure
Acute myocardial infarction
Diabetic nephropathy
Scleroderma renal crisis

Angiotensin receptor blocker (ARBs)

Losartan

Candesart
an
Irbesartan

Valsartan

Telmisarta
n

 Angiotensin receptor antagonist

AT1 and AT2
Vasoconstrictor, aldosterone
secretion and release of adrenaline
from sympathetic nerve ending
Angiotensi
n ll
(agonist)

Angiotensin
receptor
(AT1)
(competitiv
e
antagonism

ARBs
(antagoni
st)

Adverse effect

Headache
Hypotension
Weakness
Rashes
Teratogenic effect
Less likely to produce cough/
angioedema

Therapeutic use
Hypertension
Congestive cardiac failure
Myocardial infarction

Indications
Patients who develop cough with ACE
inhibitors
Patients with diabetes
Patients intolerant to ACE inhibitors

Direct renin inhibitor

Aliskire
n
Angiotensinogen

angiotensin I

Renin
Inhibit renin, hence :
Decrease level of angiotensin l and angiotensin ll

Uses :
Hypertension as monotherapy
Combination with diuretics

References
Principle of Pharmacology 2nd Edition
by HL Sharma and KK Sharma