DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

BIPHENYLMETHYL DERIVATIVES
R 2
THIENYLMETHYLACRYLIC ACID DERIVATIVE
EPROSARTAN
COOH
737
CANDESARTAN
CILEXETIL
H 3 C
O
N
N
R 1
CH
O
H 3 C
N
COOH
S
N
R 1 R 2
O
3 O
H
N
O O
N
IRBESARTAN
LOSARTAN
OLMESSARTAN
MEDOXOMIL
TELMISARTAN
H 3 C
H 3 C
N O
N
N
OH
N
Cl
O
N
O
N
HO
CH 3
CH 3
CH 3
O
O
O
N
N
N
N
H
N
N
H
N
N
H
N
N
N
N
CHAPTER 26
RENIN AND ANGIOTENSIN
N
CH 3
CH 3
CH 3
CH 3
CH 3
HOOC
N
N
N
H 3 C
VALSARTAN
O
HO
H 3 C
N
O
N
N
H
N
N
Figure 26–10. AngII receptor antagonists. Structures within red boxes are removed by esterases and replaced with a hydrogen
atom to form the active molecule in vivo. “~” indicates point of attachment to biphenyl core.
• ARBs reduce activation of AT 1
receptors more effectively than do
ACE inhibitors. ACE inhibitors reduce the biosynthesis of AngII
by the action of ACE, but do not inhibit alternative non- ACE
AngII- generating pathways. ARBs block the actions of AngII via
the AT 1
receptor regardless of the biochemical pathway leading
to AngII formation.
• In contrast to ACE inhibitors, ARBs permit activation of AT 2
receptors.
ACE inhibitors increase renin release, but block the conversion
of AngI to AngII. ARBs also stimulate renin release; however,
with ARBs, this translates into a several- fold increase in circulating
levels of AngII. Because ARBs block AT 1
receptors, this
increased level of AngII is available to activate AT 2
receptors.