Lecture 8: ACE inhibitors Flashcards
What are the pathophysiological effects of RAAS?
- Increased activity in Congestive cardiac failure and hypertension
- Adverse CV effects
i.e Cardiac hypertrophy
i.e Atherosclerosis development and plaque rupture
i.e Proinflam/pro-oxidant - Close relationship with SNS
What does ACE do in addition to ANG conversion?
ACE -> Breakdown substance P.
Substance P and Bradykinin augment NO release.
What does ANG2 do on the AT-1?
- Aldosterone
- Vasoconstriction
- Inc. salt retention
- Inc. SNS tone
- Inc. endothelin
- Inc. VSM hypertrophy
What is the MoA of ACEi?
ACE inhibitors
- Inhibit ACE
= Dec ANG2 activity and conc. of other vasoactive peptides
- Increase bradykinin levels (can be beneficial for the heart)
How do ANG2 antagonists work?
Block AT1
Where are AT1 receptors found?
- Kidney
- Heart
- Vascular SM
- Adrenal glands
What are the pathophysiological effects of ANG 2?
Cardiomyocyte
- Hypertrophy
- Increased O2 consumption
- Impaired relaxation.
Fibroblast
- Fibrosis
Peripheral artery
- Vasocon
- VSM hypertrophy
Coronary art
- Vasocon
- Atherosclerosis
What type of drug blocks AT1?
“sartan’
What are the pathophysiological effects of aldosterone?
CM
- Hypertrophy
Fibroblast
- Fibrosis
Peripheral art.
- Vasocon
- Endothelial dysf.
Kidney
- K loss
- Na retention
What happens with long term ACE use?
First few weeks plasma benefits:
- Dec ANG 2
- Dec aldo
but later
- ANG2 and aldo increase BECAUSE of chymase activity (A1-A2)
- BUT bradykinin levels increase = vasorelaxation and endothelial function inc.
Compare and contrast ACE vs AT1 blockers:
ACE
- Acutely lowers ANG2 and ALDO but chronically this is normalised
- However increased bradykinin is good.
AT1
- Non-competitive block
- Prevents ANG2 function
What are the effects of ACEi and AIIA?
Vasodilation
- Dec. art and venous pressure
- Dec. ventricular preload and afterload
Dec. blood volume
- natriuresis (lose Na)
- Diuresis
Dec. SNS activity
Dec. cardiac and vascular hypertrophy
What are some ACE inhibitors?
Main one: Cilazapril
others:
Captopril
Enalapril
etc etc
What are some AIIA?
Main one: Candesartan
- Losartan
- Valsartan
What are the considerations of ACE and AIIA?
Be careful with patients that have chronic kidney disease
What are the ACE indications?
- Hypertension (AB) + (CD)
- Congestive heart failure
Write some notes on ACE use in hypertension:
- Monotherapy then combination
- Diuretic + ACEi (Synergistic combination)
Write some notes on ACE use in HFrEF:
AS part of multiple treatments
- ACEi
- Diuretic
- Beta blocker
- Aldosterone antagonist
What are the AIIA indications?
In ACEi intolerant patients
- Hypertension
- HF
-> Candesartan licensed
-> Dont use ACEi and AIIA, C/I
What are common treatment regimes for hypertension?
Diuretic + ACEi + Vasodilator
What are some common treatment regimes for heart failure?
Diuretic + ACEi (OR AIIA) + B-blocker + Spironolactone
What are the SE of ACE?
- Dry cough (Bradykinin/Sub P stimulate C-fibres in lungs)
- Hyperkalemia
- Renal Fx deterioration
- Hypotension
- Angiooedema
What are the SE of AIIA?
- Dry cough
- Hyperkalemia
- Renal Fx deterioration
- Hypotension
- Angiooedema
What are the real cautions when using ACE and AIIA?
- Hyperkalemia
- Renal impairment
- Volume depletion / diuresed patients
Absolute contradindications
- Bilateral renal stenosis
- Pregnancy
What is bilateral renal art stenosis a C/I?
ANG2 required in these patients to constrict the efferent arteriole to maintain pressure across glomerulus. Otherwise AKI.
Why is ACE / AIIA C/I in pregenacy?
Cross placental and cause renal defects and hypotension
What are the non-BP lowering effects of ACE?
Cardio-protective
- Beneficial effects independent of lowering BP
- Reduced incidence of developing new db
Whats the role of ANG2 and db?
ANG2:
- Inc. SNS
- Pro inflam and oxidant
- Impairs insulin signalling
- Impairs pancreas function
- Reduced insulin sensitivity
Is there any added benefits of blocking renin directy?
No
