Pharmacology of Angiotensin II Receptor Blockers (ARBs)

Question 1

What drug is a Direct Renin Inhibitor (DRI)?

Answer 1

Aliskiren

Question 2

What is the MOA of Angiotensin Receptor Blockers (ARBs)

Answer 2

competitive inhibitors of AT1 receptors (may have some AT2 receptor blocking). by blocking the AT1 receptor there is an increase of Angiotensin II to activate AT2 receptor and Mas receptors

Question 3

What are the effects of AT1 receptor activation?

Answer 3

hypertensive effects
-vasoconstriction
-fibrosis
-inflammation
-oxidative stress
-cardiac hypertrophy

Question 4

What are the effects of AT1 and Mas receptor activation?

Answer 4

antihypertensive effects
-vasodilation
-antifibrotic
-anti-inflammation
-decreased oxidative stress
-antiproliferation

Question 5

What may occur with chronic ACE Inhibitor use?

Answer 5

“ACE Escape” where there is a reduced efficacy of ACEI

Question 6

What are the different effects of ARBs compared to ACEI?

Answer 6

-ARBs reduce activation of AT1 receptors more than ACEIs
-ARBs allow activation of AT2 receptors (due to blocking specifically AT1 receptors)
-ARBs increase angiotensin (1-7), but ACEIs increase it even more

Question 7

What is the Black Box Warning of ARBs?

Answer 7

fetal toxicity= do NOT use during pregnancy

Question 8

What are the adverse effects of ARBs?

Answer 8

HYPERkalemia
note ARB may be good choice for pt with history of cough or angioedema with ACEI

Question 9

Describe the chemistry of Losartan

Answer 9

-~14% of oral dose is converted to an active metabolite
-nonpeptide, selective and competitive AT1R antagonist

Question 10

What are the indications of Losartan?

Answer 10

-HTN
-HTN with left ventricular hypertrophy
-nephropathy in T2DM
only ARB in class proven to lower chance of stroke

Question 11

Describe the chemistry of Valsartan

Answer 11

-nonpeptide
-best ARB for potency and selectivity
-noncompetitive antagonist (binds allosteric site)

Question 12

What are the indications of Valsartan?

Answer 12

HTN

Question 13

Describe the chemistry of Candesartan

Answer 13

-nonpeptide selective
-inactive prodrug: candersartan cilexetil

Question 14

What are the indications of Candesartan?

Answer 14

HTN (stronger BP lower effects then losartan)

Question 15

Describe the chemistry of Telmisartan

Answer 15

-nonpeptide
-high specificity and affinity
-long t1/2 = 24 hours
-crosses BBB (alzheimer’s disease?)

Question 16

What are the indications of Telmisartan?

Answer 16

-HTN
-CV risk reduction

Question 17

Describe the chemistry of Eprosartan

Answer 17

-nonpeptide
-modified more closely resemble Angiotensin II (“decoy”)
-competitive AT1 receptor antagonist

Question 18

What are the indication of Eprosartan?

Answer 18

HTN

Question 19

Describe the chemistry of Azilsartan medoxomil

Answer 19

-selective
-prodrug= azilsartan is active form
-sustained BP control over 24 h

Question 20

State ARBs affinity for AT1 receptor from least to most affinity:

Answer 20

lowest: losartan, eprosartan
-telmisartan
-irbesartan
-azilsartan, candesartan
-olmesartan
highest: valsartan