7/29/2019 Angiotensin II Receptor Antagonist
1/22
Angiotensin II receptorantagonist
The renin-angiotensin system (RAS) orthe renin-angiotensin-aldosterone
system(RAAS) is a hormone system thatregulates blood pressure and water (fluid)
balance.
7/29/2019 Angiotensin II Receptor Antagonist
2/22
Angiotensin II receptorantagonist
7/29/2019 Angiotensin II Receptor Antagonist
3/22
Angiotensin II receptorantagonist
When blood volume is low, the kidneys
secrete renin.
7/29/2019 Angiotensin II Receptor Antagonist
4/22
Angiotensin II receptorantagonist
Renin stimulates the production
of angiotensin.
7/29/2019 Angiotensin II Receptor Antagonist
5/22
Angiotensin II receptorantagonist
Angiotensin causes blood vessels to
constrict, resulting in increased blood
pressure.
7/29/2019 Angiotensin II Receptor Antagonist
6/22
Angiotensin II receptorantagonist
Angiotensin also stimulates the secretion
of the hormone aldosteronefrom
the adrenal cortex.
7/29/2019 Angiotensin II Receptor Antagonist
7/22
Angiotensin II receptorantagonist
Aldosterone causes the tubules of the
kidneys to increase the re-absorption of
sodium and water into the blood.
7/29/2019 Angiotensin II Receptor Antagonist
8/22
Angiotensin II receptorantagonist
This increases the volume of fluid in the
body, which also increases blood
pressure.
7/29/2019 Angiotensin II Receptor Antagonist
9/22
Angiotensin II receptorantagonist
If the renin-angiotensin-aldosterone
system is too active, blood pressure will
be too high.
7/29/2019 Angiotensin II Receptor Antagonist
10/22
Angiotensin II receptorantagonist
If the renin-angiotensin-aldosterone
system is too active, blood pressure will
be too high.
7/29/2019 Angiotensin II Receptor Antagonist
11/22
Angiotensin II receptorantagonist
Activation
The system can be activated when there is aloss of blood volume or a drop in blood
pressure (such as in hemorrhage).
7/29/2019 Angiotensin II Receptor Antagonist
12/22
Angiotensin II receptor
antagonist
7/29/2019 Angiotensin II Receptor Antagonist
13/22
Angiotensin II receptorantagonist
If the perfusion of the juxtaglomerularapparatus in the kidney's macula
densa decreases, then the juxtaglomerular cells
release the enzyme renin.
7/29/2019 Angiotensin II Receptor Antagonist
14/22
Angiotensin II receptorantagonist
Renin cleaves a zymogen, an inactive peptide,called angiotensinogen, converting it into angiotensin I.
Angiotensin I is then converted to angiotensinII by angiotensin-converting enzyme (ACE) which is found
mainly in lung capillaries.
7/29/2019 Angiotensin II Receptor Antagonist
15/22
Angiotensin II receptorantagonist
Angiotensin II is the major bioactive product of therenin-angiotensin system, causing these cells to
contract along with the blood vessels surrounding
them and causing the release of aldosterone from
the adrenal cortex.
7/29/2019 Angiotensin II Receptor Antagonist
16/22
Angiotensin II receptorantagonist
Angiotensin II acts asan endocrine, autocrine/paracrine,
and intracrine hormone.
7/29/2019 Angiotensin II Receptor Antagonist
17/22
Angiotensin II receptorantagonist
Their main use is in hypertension (high bloodpressure), diabetic nephropathy (kidney damage
due to diabetes) and congestive heart failure.
7/29/2019 Angiotensin II Receptor Antagonist
18/22
Angiotensin II receptor
antagonistThese substances are AT1-receptor antagonists
that is, they block the activation of angiotensin II
AT1 receptors.
7/29/2019 Angiotensin II Receptor Antagonist
19/22
Angiotensin II receptor
antagonistBlockade of AT1 receptors directly
causes vasodilatation, reduces secretion
of vasopressin, reduces production and secretionof aldosterone, amongst other actions the
combined effect of which is reduction of blood
pressure.
7/29/2019 Angiotensin II Receptor Antagonist
20/22
Angiotensin II receptor
antagonistPressor Inhibition
Valsartan 80 mg 30%
Telmisartan 80 mg 40%Losartan 100 mg 2540%
Irbesartan 150 mg 40%
Irbesartan 300 mg 60%
Olmesartan 20 mg 61%
Olmesartan 40 mg 74%
7/29/2019 Angiotensin II Receptor Antagonist
21/22
Angiotensin II receptor
antagonistAT1 affinity
Losartan 1000 fold
Telmisartan 3000 foldIrbesartan 8500 fold
Olmesartan 12500 fold
Valsartan 20000 fold
7/29/2019 Angiotensin II Receptor Antagonist
22/22
Angiotensin II receptor
antagonist