What does the RAAS regulate?

1.  BP

2.  Blood Volume

3. F&E Balance

Can promote cardiovascular pathology.

What are the 2 things produced by the RAAS system?

1.  Angiotensin II

2.  Aldosterone

What are the 2 enzymes that produce angiotensin II

1.  Renin

2.  angiotensin I

How does Aldosterone work?

Acts on kidneys to promote retention of H20 and Na.

Can also cause cardiovascular pathology.

How does RAAS increase BP?

1.  Vasoconstriction

2.  Increase in blood volume

ACE Inhibitors are beneficial in lowering BP how?

1.  Block conversion of angiotensin I to angiotensin II

2.  Blocks kinase II (name for ACE when substrate is bradykinin)

 3.  Suppress Aldosterone Release

Result is vasodilitation and decreased blood volume.

What problems do ACE's and ARB's treat?

What are they used to prevent?

1.  HTN

2.  Heart Failute

3. MI

4. Est. Diabetic Nephropathy

1.  MI

2.  Stroke

3.  Death from CV causes in pt's at high risk for CV event

4.  Reduce risk of Diabetic Retinopathy

What are ACE's and ARB's NOT effective for?

1.  Primary HTN of Diabetic Nephropathy

What is a common first-dose side effect when using ACE's?

Significant first-dose hypotension by causing a sharp decrease in circulating angiotensin II

What is the most common reason for dc'ing ACE Inhibitors?

Cough secondary to accumulation of bradykinin.

What is the common side effect of ACE's when they suppress Aldosterone release? 

Hyperkalemia

Are ACEI's safe during pregnancy?

Absolutely NOT!  Cause fetal malformations.

What do ARB's affect?

Block actions of:

1.  blood vessels

2.  adrenals

3.  all other tissues

How are ARB's similar to ACE's?

1.  Cause vasodilation

2.  Suppress Aldosterone release

3.  Promote excretion of Na & H20

4. Reduce Bp

5. Cause birth defects

6. Angioedema

How do ARB's differ from ACE's?

Do not cause cough or hyperkalemia

How do DRI's (direct renin inhibitor) work?

(Aliskiren)

Binds tightly with renin inhibiting cleavage of angiotensinogen into angiotensin I. 

Result?  Suppresses entire RAAS

How are the ACE's, ARB's, and DRI's alike?

1.  Vasodilitation

2.  Suppresses aldosterone release

3.  promotes excretion of h20 and na

4.  reduces bp

5.  causes birth defects

6.  angioedema

3. 

Given the similarities of ACE's, ARB's, and DRI's, are they interchangeable?

No.

What are two common aldosterone antagonists?

1.  Spironalactone

2.  Eplerenone

By blocking aldosterone receptors, aldosterone antagonists do what?

1.  Promote renal excretion of h20 and na - dec BP

2.  prevent or reverse pathologic effects of aldosterone on cv structure and function.

What are some advantagesa of using ACE's?

1.  Don't interfere with CV reflexes

2.  exercise ok

3.  no orthostatic BP

4.  no problems with asthma

5.  No hypokalemia

6.  No hyperuricemia

7.  No hyperglycemia

What is one of the most important benefits of ACE's?

Reduce risk of CV mortality secondary to HTN

What is the only ACE used for slowing progression of renal disease?

Captopril

Which ACE is used to prevent MI, Stroke, Death in pt's with high CV risk?

Ramipril (AltaCE)

Which ACE is used to treat Diabetic Retinopathy?

Enalopril

When are ACE's contraindicated with renal failure?

When pt has bilateral renal artery stenosis

What are the common drugs that ACE's interact with?

1.  Diuretics - intensify 1st dose effect

2.  Antihypertensives - additive dec BP effect

3.  Drugs that raise K+ - additive to inc K+

4  Lithium - toxicity

5.  NSAIDS - blunt antihypertensive effects

What is the one possible serious SE of ARB's?

Cancer

What is the first RAAS drug of choice?

ACE's over ARB's.

ARB's for those who can't tolerate ACE's

What is the one DRI drug available?

Aliskirin

What is Aliskirin approved to treat?

Only HTN

What are the SE's of DRI's?

Tolerated well

Maybe some diarrhea

What is the first selective aldosterone antagonist?

Eplerenone

CYP34A causes toxicity with which RAAS drug?

Eplerenone

Which two ACE's are NOT prodrugs?

Lisinopril and Fosinopril

What is the one blood dyscrasis you should watch for with ACE's

agranulocytosis - so watch for infection

Which group of RAAS drugs end in "pril"?

ACE's

Which group of RAAS drugs end in "sartan?"

ARB's

Can you prescribe ACE + ARB + DRI or any combination?

No, ONLY one at a time