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Flashcards in ACE inhibitors Deck (31):
1

RAAs system regulates?

Blood pressure
Intravascular volume/NA+/K+
Fetal development

Junta-glomerular cells
- reduce circulating renin
Locally produced - RAA
- myocardium, vascular endothelium, adrenal

2

Pathophysiological effects of RAAS

increased activation in CCF (congestive heart failure) and in hypertension
Adverse cardiovascular effects
- cardiac hypertrophy
- atherosclerosis development and plaque rupture
- pro inflammatory / pro-oxidant
Close relationship with sympathetic nervous system

3

The AT1 vs AT2 receptor

angiotensin II acts on the AT1 receptor to mediate adverse properties e.g. aldosterone secretion, vasoconstriction and classic angiotensin actions (increase synthetic tone, oxygen stress, hypertrophy)
Whereas binding to the AT2 receptor seems to have antagonistic effects to the AT1 receptor = anti proliferation, tissue repair, apoptosis, vasodilation, kidney development

4

ACE inhibitors

stop conversion of AT1-2 but they also prevent breakdown of bradykinin and substance P and therefore ACE inhibitors will increase their plasma levels, also by blocking ACE you shunt angiotensin down another synthetic pathway mediated by a different enzyme which can also have beneficial effects e.g. lowering BP, anticoagulants

5

Angiotensin II antagonists inhibit?

angiotensin II antagonists type I receptors

6

Why do renin levels increase when you take ACE inhibitors?

Because with lack of negative feedback from ACE inhibitors you get pressure to keep synthesising angiotensin I

7

Angiotensin II effects on cardiac myocytes

Hypertrophy
apoptosis
cell sliding
increased wall stress
Increased O2 consumption
Impaired relaxation

8

angiotensin II effects on fibroblasts

hyperplasia
collagen synthesis
fibrosis

9

angiotensin II effects on peripheral artery

vasoconstriction
endothelial dysfunction
hypertrophy
decreased compliance

10

angiotensin II effects on coronary artery

Vasoconstriction
Endothelial dysfunction
Atherosclerosis
Restenosis
Thrombosis

11

Where are type I angiotensin receptors found

kindly, heart, vascular smooth muscle, brain, adrenal glands, adipocytes, placenta

12

where are type II angiotensin receptors found?

heart, adrenal, CNS, kidney

13

Effects of aldosterone on cardiac myocytes

hypertrophy, NE release

14

Effects of aldosterone on fibroblasts

hyperplasia, collagen synthesis, fibrosis

15

Effects of aldosterone on peripheral artery

vasoconstriction
endothelial dysfunction
hypertrophy
decreased compliance

16

Effects of aldosterone on the kidney

potassium loss
sodium retention

17

ACEi benefits short and long term

plasma effects in the first few weeks
- dec AII conc
- dec Aldosterone conc
But later
- return to normal AII and aldosterone
- due to chemise activity
- what about local tissue levels
But bradykinin levels increase (vasorelaxation, endothelial function increase)

18

ACE drug types NZ

Cilazapril 0.5-5mg od

19

AIIA drug types NZ

candesartan 4-32mg od

20

candesertan and losartan excretion

renal 60%
Bile 40%

21

ACE indications

hypertension
congestive heart failure

22

AIIA indications

ACEi intolerant patients
hypertension
heart failure

23

why should you never combine ACEi and AIIA

so significant improvement and you argument adverse side effects
esp. hyperkalemia

24

ACEi side effects

side effects can take a while to manifest so you have to keep monitoring patients
If they develop cough (probably due to inc Brady kinin and substance P) on ACE inhibitor then swap them to angiotensin II antagonist where chance of cough is much lower
- hyperkalemia
- Renal Fx deterioration
- Hypotesion
- Angio-edema
- Contra indicated pregnancy

25

common treatment regime for hypertension

Diuretic + ACE inhibitor + vasodilator

26

Common treatment regime for heart failure?

Diuretic + ACE inhibitor + beta-blocker + spironolactone +/- AII antagonist

27

AII antagonists

Dry cough
Hyperkalemia
Renal Fx deterioration
Hypotension
Angio-edema
contra-indicated pregnancy

28

Absolute contraindications to use of ACEi or AIIA

- pregnancy: 2nd and 3rd trimester, renal defects, oligohydroaminos, fatal death.
- Bilateral renal artery stenosis: this you cant test for so have to monitor patient really closely when you start them on the drug. Efferent arteriole tone is very high so to maintain glomerular filtration pressure when renal artery narrow. but giving said drugs will cause relaxation of efferent arteriole = rapid deterioration in renal function

29

ACEi and AIIA possible non-BP lowering effects?

Reduce incidence of developing new diabetes

30

How can angiotensin II lead to the development of diabetes?

Oxidant stress
Pro-inflammation
Increase sympathetic activity
Impaired insulin signalling
Impair pancreatic function
Reduced insulin sensitivity

31

A renin inhibitor?

Aliskiren available in US + EU is a renin inhibitor