ARB, ACE-I & Renin-I Pharmacology

Question 1

Angiotensinogen is converted to what substance by what enzyme?

Answer 1

It is converted to Angiotensin 1 by Renin

Question 2

Where is Renin produced?

Answer 2

Kidneys

Question 3

Agiontensin 1 is converted to Angiotensin 2 by what enzyme?

Answer 3

Angiotensin Converting Enzyme

Question 4

Angiotensin 2 has what effects?

Answer 4

Vasoconstriction, Aldosterone secretion, Sympathetic activation

Question 5

What cells in the kidney contain Renin?

Answer 5

Juxtaglomerular Apparatus

Question 6

Where does Renin cleave Angiotensin?

Answer 6

Between Leucines on C end of peptide

Question 7

Where does ACE cleave Angiotensin 1 to make Angiotensin 2?

Answer 7

Between the Phe and His on the C side of the peptide

Question 8

What does the macula densa sense as plasma passes?

Answer 8

NaCl concentration of plasma

Question 9

Renin is activated in what larger physiologic condition?

This is sensed by what portion of the kidney?

Answer 9

Low sodium conditions

Macula Densa

Question 10

What other portions of the Kidney can cause Renin release?

Answer 10

Intrarenal Baroreceptor in Pre-glomerular vessels

Question 11

Activation of what adrenergic receptors cause increased Renin release?

Answer 11

B1 Adrenergic receptors on Juxtaglomerular cells

Question 12

What is the mechanism to recognize enough Renin has been released?

Answer 12

AT1 receptor on Juxtaglomerular cell activated by Angiotensin 2

Question 13

What receptor mediates the majority of response from Angiotensin 2?

Answer 13

AT1

Question 14

What effects does activation of AT1 receptor have? (5 items)

Answer 14

Vasoconstriction
Vascular proliferation
Aldosterone secretion
Cardiac myocyte proliferation
Increased sympathetic tone

Question 15

What effects does activation of AT2 receptor have? (3 items)

Answer 15

Vasodilation
Antiproliferation
Apoptosis

Question 16

What is the second messenger process of the AT1 receptor?

Answer 16

AT1 activation (G-protein coupled) –> PIP2 –> IP3 + DAG –> IP3 activates Ca2+ & DAG activates PKC

Question 17

Where is the AT1 receptor located in the Adrenergic synapse? What effect does it have?

Answer 17

The AT1 receptor is pre-synaptic & post-synaptic. Its activation by ANG2 results in increased release of NE which activates postsynaptic alpha1 receptors. ANG2 also activates post-synaptic AT1 receptors which have a director vasoconstrictor effect.

Question 18

What is Aldosterone’s effect on the kidney?

Answer 18

Reabsorption of Na and Water in intercalated cells of collecting duct

Question 19

What are the broad effects of RAAS Inhibitors? (4 items)

Answer 19

Blood pressure lowering related to plasma renin activity
Decrease blood pressure with no change in heart rate
Can cause hypotension
Can cause fetal wasting in pregnancy

Question 20

RAAS inhibition can occur in three locations in the RAAS pathway. What are they?

Answer 20

Direct inhibition of Renin release
Inhibition of ACE conversion from Ang1 to Ang2
Blockade of Angiotensin receptor

Question 21

What is the hallmark AT1 receptor blocker medication?

Answer 21

Losartan

Question 22

What type of inhibition does Losartan produce on AT1 receptors? What ramifications does this have?

Answer 22

Competitive inhibition

Increased Angiotensin 2 production can overcome the Losartan inhibition of AT1

Question 23

What is the mechanism of action of Losartan?

What effects does this produce? (3 items)

Answer 23

Angiotensin 2 receptor (AT1) competitive inhibition

1. Decreased aldosterone secretion
2. Decreased vasoconstriction
3. Decreased sympathetic activation

Question 24

Does Losartan and other ARBs work immediately? If not, how long do they take to create maximal effect?

Answer 24

No, 4 weeks

Question 25

What adjunct medication is frequently used to increase BP lowering effect?

Answer 25

Diuretics

Question 26

What are the hallmark ACE inhibitors for this course? (3 items)

Answer 26

Captopril Enalapril Lisinopril

Question 27

ACE inhibitors prevent production of what substance from what substance?

Answer 27

They prevent production of Ang2 from Ang1

Question 28

What diagnostic would you check to decide if and ARB or ACE-inhibitor is indicated instead of another HTN medication?

Answer 28

Draw plasma Angiotensin 2 levels to check for inappropriate elevation.

Question 29

How do black individuals' response to ACE-I and HCTZ compared to non-black individuals?

Answer 29

The percentage of blacks who are responders to ACE-I is significantly less while the percentage who respond to an HCTZ type diuretic was slightly increased. Percentage for combination was about the same.

Question 30

What is the effect of ACE-I on CHF mortality?

Answer 30

40% reduction after 6 months

Question 31

What effect did ACE-I (Captopril) have after acute MI? (2 items)

Answer 31

Reduction in mortality AND Reduction in LV dysfunction

Question 32

How do ACE-I compare with other vasodilator therapy in CHF therapy?

Answer 32

Overall reduction in mortality

Question 33

What is the most common adverse effect of ACE-I?

Answer 33

Cough

Question 34

What are the #2-5 common adverse effects of ACE-I? (4 items)

Answer 34

2. Rash 3. Taste Disturbance 4. Angioedema 5. Proteinuria

Question 35

Why would an ACE-I exacerbate renal dysfunction/failure?

Answer 35

If the failure is a result of poor perfusion from the Renal artery, ACE-I will prevent compensation to improve perfusion.

Question 36

What is the hallmark Renin inhibitor for this course?

Answer 36

Aliskiren

Question 37

What is the mechanism of action of Aliskiren?

Answer 37

Aliskiren occupies the binding site for Angiotensinogen on Renin preventing conversion/production of Angiotensin 1.

Question 38

Does Aliskiren increase/decrease/not change systolic, diastolic and HR?

Answer 38

Decreases both systolic and diastolic | Doesn't change HR

Question 39

On what cells in the kidney are Spironolactone and Eplerenone active?

Answer 39

Principal cells and Intercalated cells

Question 40

What effect does Spironolactone and Eplerenone have?

Answer 40

Inhibition of the renal and extra renal actions of aldosterone (including Na and Water retention)