Angiotensin converting enzyme inhibitors

Question 1

What are two mechanisms of blocking the RAAS?

Answer 1

ACE inhibitors

Angiotensin II antagonists

Question 2

Where is renin released from

Answer 2

The juxtaglomerular cells in the kidney

Question 3

What causes the JG cells to release renin (3 mechanisms)

Answer 3

1) Low extracellular volumes detected by baroreceptors in the afferent arteriole of the kidney
2) Low extracellular volumes detected by cardiac and arterial baroreceptors which result in sympathetic activation and increase in circulating catecholamines–> activation of beta-1 receptors in kidneys–> renin release
3) Macula densa cells in the early distal tubule that sense reduction in Cl- concentration

Question 4

What does angiotensin II bind to

Answer 4

Angiotensin type I and type II receptors. Type I receptor activation results in aldosterone release from the adrenal glands and other classical effects (vasoconstriction, sympathetic activation). Type II receptor more sparse, upregulated in injury causes counter effects –> vasodilation and natiuresis.

Question 5

What does aldosterone bind to and what is its main effect

Answer 5

Mineralcorticoid receptors located in many tissues. Main effect is via MR receptor in kidneys whereby on activatioin there is upregulation of Na+ channels increasing Na+ reabsorption and K+ loss.

Question 6

What are the effects of aldosterone not related to Na+ reabsorption

Answer 6

-Vasoconstriction, endothelial dysfunction, decreased
compliance and hypertrophy of peripheral arteries.
-Hyperplasia and fibrosis from fibroblasts.
-Hypertrophy and norepinephrine release from cardiac myocytes.

Question 7

Describe how ACEi work

Answer 7

Initially by blocking conversion of angiotensin I to II. This effect causes reduced Angitensin II and aldosterone levels in the first few weeks. Then Chymase takes over the conversion. Secondary effects is via the increase in bradykinins. ACE breaks down bradykinins so inhibition of this increases levels- bradykinins are vasodilators via release of NO and prostacyclin.

Question 8

Name two ACEi

Answer 8

Cilazapril

Captopril

Question 9

What are six effects of ACEi and AIIA

Answer 9

V asodilation
Decrease arterial and venous pressure
Decrease ventricular preload and afterload
Decrease blood volume through natiuresis and dieuresis
Decrease sympathetic activity
Decrease cardiac and vascular hypertrophy

Question 10

ACEi indications

Answer 10

HTN (monotherapy or with a diuretic)

CHF (multiple therapy with diueretic, beta blocker, and aldosterone antagonist)

Question 11

AIIA indications

Answer 11

When ACE inhibitor not tolerated (more evidence that ACEi improve outcomes)

Question 12

Common treatment regime for CHF

Answer 12

Diuretic, beta blocker, ACEi, sprironolactone (aldosterone antagonist)

Question 13

Side effects of ACEi

Answer 13

Dry cough (due to bradykinin increase)
Hyperkalemia
Renal function deterioration (due to decreased perfusion)
Hypotension
Angiodema (bradykinins)

Question 14

Absolute contraindications for ACEi and AIIA

Answer 14

Pregnancy (AII invovled in fetal renal development)

Bilateral renal artery stenosis

Question 15

What is the relationship between ACEi and diabetes

Answer 15

Reduction in diabetes risk as Angiotensin II causes pro-inflammation, increased sympathetic activity, impaired insulin signalling, impari pancreatic functioning and reduced insulin sensitivity.

Question 16

Name two AIIA

Answer 16

Losartan

Valsartan