Antihypertensive Drugs Acting On Raa

Front 1

Step-wise, where do RAA acting drugs fall under Antihypertensive Therapy?

Back 1

Step I

Front 2

Why is the Renin-Angiotensin-Aldosterone (RAA) System important?

Back 2

Regulates:
BP
Blood volume
Electrolyte Balance

It also mediates pathophysiological changes associated with:
HTN
Heart Failure
MI

Front 3

How does the RAA regulate BP?

Back 3

1. Renin is released from kidney when BP drops
2. Renin catalyzes the formation of angiotensin I from angiotensinogen. (Note this is the rate limiting step for angiotensin II)
3. Angiotensin I is converted to angiotensin II (a potent vasoconstrictor, increases BP)
4. Angiotension II stimulates the adrenal cortex, which produce aldosterone.
5. Aldosterone acts on the kidney.
6. Kidneys retain Na and water.
7. BP is raised.

Front 4

How do the baroreceptos (carotids and aorta) react to BP being increased?

Back 4

React to low BP by increasing sympathetic activity

(Beta = cardiac stimulation, alpha = peripheral vasoconstriction)

Front 5

Which drugs act on the RAA?

Back 5

-Angiotensin Conversting Enzyme (ACE) inhibitors
-Angiotensin II Receptor Blockers (ARBs)
-Direct Renin Inhibitors (DRIs)

Front 6

How do Angiotension Converting Enzyme (ACE) Inhibitors work?

Back 6

1. Completely block the angiotensin I converting enzyme
2. Prevents the production of angiotensin II which is a powerful vasoconstrictor

Front 7

ACE inhibitor Prototype

Back 7

Lisinopril

Front 8

Lisinopril Indications

Back 8

-Essential HTN with normal renal function
-HF: used with digoxin and diuretics
-Diabetes (renal protection)

Front 9

What electrolyte can elevate with ACE Inhibitor use?

Back 9

Potassium

Front 10

What other drug is used with Lisinopril to counteract K retention?

Back 10

A Thiazide or loop diuretic

Front 11

ACE inhibitors SE

Back 11

- Hyperkalemia
- Dry cough (occurs in about 1/3 of patients)
- Angioedema (from accumulation of bradykinin secondary to inhibition of kinase II)

Front 12

How do Angiotensin II Receptor Blockers (ARBs) work?

Back 12

They produce vasodilation via smooth muscle relaxation

Front 13

How are ACEs & ARBs different?

Back 13

ACE inhibit production of angiotensin II from Angiotensin I

ARBs block the actions of angiotensin II

Unlike ACEs, ARBs are specific and WORK ON THE RECEPTORS!

Front 14

What is the suffix for ARBs?

Back 14

"-Sartan"

Front 15

ARBs Prototype

Back 15

Iosartan (Cozaar)

Front 16

Who are good candidates for ARBs?

Back 16

Patients who are allergic to ACEs and develop angioedemas and coughs.

* ARBs still produce angioedemas, but the incidence is lower

Front 17

ARBs Indications

Back 17

-HTN
-Heart Failure
-Diabetic nephropathy
-MI
-Stroke prevention

Front 18

ARBs Pros

Back 18

– Reduce salt and water volume
– Less SE than ACE
– Does not retain K as much as ACE
– Same Diabetes Mellitus renal protection as ACE

Front 19

How do Direct Renin Inhibitors (DRIs) work?

Back 19

Binds with renin, inhibiting change from angiotensinogen to angiotensin I

Front 20

Are DRIs and ACEs similar?

Back 20

Yes! DRIs also stop the whole RAAS cascade from the top. So, same as ACE-I, just work in a different place and more expensive.

Front 21

DRI Prototype

Back 21

Aliskiren (Tekturna)

Very new & expensive!

Front 22

Aliskiren Indications

Back 22

HTN

Front 23

Aliskiren SE

Back 23

- Cough
- Hyperkalemia
- Angioedema
- Dose dependent diarrhea

(Same SEs as ACE)

Front 24

Why is angioedema a prevalent SE in drugs that act on the RAA system?

Back 24

Bradykin, a peptide and potent vasodilator increases vascular permeability, leading to rapid accumulation of fluid in the interstitium. This leads to angioedemas!

Drugs like ACE inhibitors, for example, block ACE, the enzyme that among other actions, DEGRADES bradykinin