ACE inhibitors

Question 1

What does renin-angiotensin system do?

Where is renin produced

Answer 1

regulates blood pressure, intravascular volume (Na/K)
Renin is produced in JG cells, also locally produced in myocardium, vascular endothelium and adrenal cortex

RAAS system on - will increase blood pressure ( by vasoconstriction and increased fluid absorption)

Question 2

What can go wrong? and when do we need to control this?

Answer 2

In patient with increase CCF and hypertension
-also if they have cardiac hypertrophy, atherosclerosis

Need to have inhibitors to stop effects as can make some of these things worse

Question 3

How does RAAS pathway work

Answer 3

Renin breaks down angiotensin –> angiotensin 1
ACE enzyme converts A1- A2
A2 acts on AT-1 receptor and AT-2 receptor
AT-1 receptor - aldosterone secretion, vasoconstriction
AT-2 receptor - more of a inhibitor of effects above

Question 4

What things will change when use an ACE inhibitor

Answer 4

• get increased bradykinin (because it is not being broken down)
• also increased angiotensin (1-7) proteins which have antihypertensive effects and anti proliferative effects

Question 5

What do ace inhibitors do?

Answer 5

-they inhibit angiotensin converting enzyme so cannot get angiotensin 1 to angiotensin 2

Question 6

How can aldoesterone do negative feedback?

Answer 6

Aldoesterone - can inhibit further renin secretion

Question 7

Agiotensin 2 antagonits

Answer 7

-will inhibit angiotensin 2 type 1 receptors (cause vasoconstrciton, aldeosterone secretion, and other actions)

Question 8

Angiotensin 2 effects

Answer 8

• Increase SNS activity
• increase tubular na, cl resportion and k secretion, and h2o retenion
• causes aldosterone secretion (increase na/k atpase pump)
• arteriolar vasoconstriction, increase in blood pressure - resistance vessels
• adh secetion - more water absrobedin collectign duct

Question 9

Pathophysiological effects of angiotensin 2

Answer 9

cardiac myocyte remodelling - hypertropy, apoptosis
increases fibrosis, collagen
-vasoconstriction of artereis and coronary arteries

Question 10

Angiotensin 2 activity - what is anotehr psotivie effect

Answer 10

• blocks receptor 1

- howver can increase receptor 2 , and these are beneficial effects - tissue repair, antirpolireraiton, vasodilation

Question 11

Aldoesterone effects

Answer 11

-similar to angiotensin 2 - adverese

Question 12

How it works - ace inhibitor

Answer 12

• starts to decrease A2 and aldosteorne btu after time tehse increase back to normal levels
• bradykinin - increases, due to shutnign to AT (1-9) to be made
• maybe decreases in tissue level

Question 13

Cilazapril

Answer 13

ace inhibitor

Question 14

Cilazapril

Answer 14

ace inhibitor

-pro drug

Question 15

effects of these

Answer 15

• decrease blood pressure (vasodilation)
• decrease blood volume
• decrease SNS
• decrease cardiac and vascular hypertrophy

Question 16

When do we use ACE inhibitor

Answer 16

-Hypertension - first line therapy with diuretic

Question 17

When do we use ACE inhibitor

Answer 17

• Hypertension - first line therapy with diuretic
• also used for CCF - normally on an ace inhibitor, diuretic, beta blocker and aldosterone antagonist (for impaired systolic function)

Question 18

When do we use AG2 inhibitor

Answer 18

• when patient cannot tollerate an ace inhibitor
• for hypertension
• for heart failrue

Question 19

Side effects of Ace inhibitors

Answer 19

• dry cough (due to increase bradykinin)
• hyperkalaemia
• renal deterioation
• hypotension
• swap to angiotensin 2

Question 20

Contradiciton for ACEi and A2A - renal stneosis

Answer 20

• angiotensin 2 causes vasoconstriction of the efferent arteriol - sets up presure gradient - help filter blood
• renal artery stenosis - can get afferent arteriol getting reduced perfusion
• that reduction will result in an increase in angiotensin 2 to maintian GFR pressure
• if anatgonise this - will get no constriction of efferent arterol - getting drop in renal gradeient and deterioration in renal funciton
• So do not give ace inhibitrs - measure cratinein and potaisum to see renal fucniton