Adrenergic & Angiotensinogen Block in CHF

Question 1

What effect do ACE inhibitors have on angiotensin II and bradykin?

Answer 1

Block angiotensin II activation by ACE (decrease)

Prevent bradykinin degradation by kinase II (increase)

Question 2

What does angiotensin II do?

Answer 2

Angiotensin II = one of most powerful vasoconstrictors

  - stimulates aldosterone/ ADH secretion
  - stimulate epinephrine/ NE
  - increase thirst

(Everything to increase CO/ preload)

Question 3

What does bradykinin do?

Answer 3

Bradykinin = one of most powerful vasodilators
-helps prevent remodeling of heart
(decrease afterload)

Question 4

Where are renin and angiotensinogen (precursor) secreted?

Answer 4

1) angiotensinogen = made in liver

2) renin = made kidney

Question 5

Name the three important ACE inhibitors (hint: -pril) and rank by their general dosing

Answer 5

Lisinopril: once a day
Enalapril: twice a day
Captopril: 3 times a day

Question 6

If you want to know if a patient can tolerate ACE inhibitors, which one should you give them?

Answer 6

Captopril

-not as long acting so you can see if they get too hypotensive

Question 7

What are the side effects of ACE inhibitors?

Answer 7

• cough (switch to ARB)
• hyperkalemia (lose fluid or dehydrated)
• angioedema (immune mediated)
• renal dysfunction (not absolute contraindication)
• hypotensive

Question 8

T/F: patient should take NSAIDS to help with heart failure

Answer 8

False!

-affect prostaglandins and could affect kidneys

Question 9

What other drugs should be avoided with ACE inhibitors?

Answer 9

Salt related things:

• Lithium
• Salt substitute
• Loop diuretics
• K sparing diuretics

Question 10

Which patients should not be prescribed ACE inhibitors?

Answer 10

• pregnant
• bilateral renal artery stenosis
• maybe not kidney dysfunction
• angioedema
• hyperkalemia

Question 11

What are the clinical results from using beta inhibitors? (what outcome does it reduce)

Answer 11

Reduce hospitalization/ death
Reduce all cause mortality

*more severe- the greater the benefit

Question 12

Do we see a greater benefit from “pushing the dose” of ACE inhibitors?

Answer 12

No significant benefit- can use lower dose

contrasted to beta blockers

Question 13

What are three ARBs you could prescribe? Which ones are only taken once/ day?

Answer 13

Candesartan*
Losartan*
Valsartan

• once a day

Question 14

What’s the rational for ARB’s to block the angiotensin II RECEPTOR? which specific receptor do they block?

Answer 14

Avoid “angiotensin escape” = increasing doses can lead to increased angiotensin II (opposite of what you want)

Block angiotensin II receptor AT1 (in lungs, smooth muscle, liver, brain kidney)

Question 15

Most of the actions/ side effects are the same between ARBs and ACEIs and both are used with HFrEF. But what side effects is different with ARBs?

Answer 15

No cough
less angioedema
increased excretion of uric acid

Question 16

Why would you use a Beta blocker with someone with heart failure?

Answer 16

To compensate to the low flow, the adrenergic system is stimulated which overworks heart
-leads to remodeling & toxic effects

Beta blockers prevent this - shield against NE

Question 17

What are the different sympathetic receptors and where are they?

Answer 17

Beta 1 = on myocte, stimulate G proteins
-only one to do myocyte apoptosis, some toxic effects
Beta 2 = on myocyte, stimulate G proteins
-some toxic effects
Alpha = on nerve

Question 18

What are the different classes of Beta blockers and what do they do?

Answer 18

Generation 1: non-selective for B1/ B2- no ancillary
properties
Generation 2: non-selective for B1/ B2- no ancillary
properties. ie: atenolol
Generation 3: selective or non-selective for B1/ B2- ancillary
properties. ie: carvedilol
Generation 4: haven’t made them yet- “designer drugs”

Question 19

In someone with respiratory disease, you want to use a BB more selective for beta 1 (beta 2 is more in lungs). Which medications are more selective for beta 1?

Answer 19

Nebivolol

Bisoprolol

Question 20

Which are the only beta blockers proven to help with heart failure

Answer 20

Bisoprolol
Carvedilol
Metoprolol succinate

Question 21

What patient is an appropriate candidate for beta blockers?

Answer 21

• mild to moderate symptoms of heart failure (NYHA II-IV)

- Systolic dysfxn of LV

Question 22

What are the positive clinical outcomes of beta blockers?

Answer 22

Improve ejection fraction
reduce mortality/ morbidity (push the dose!)
keep you out of hospital

Question 23

LCZ696 is a combination of two drugs. Which ones?

Answer 23

ARB (valsartan) + neprolysin inhibitor

Question 24

What is the function of LCZ696 (sacubitril/valsartan)?

Answer 24

ARB = block AT1 receptor (decrease vasoconstriction, BP, sympathetic system, fibrosis/ hypertrophy, etc.)

Neprolysin inhibitor (sacubitril) = prevent inactivation of BNP (which has the positive effects of vasodilation; decrease BP, symp. tone, fibrosis/ hypertrophy, and does diuresis)

Question 25

What are the indications/ contraindications of LCZ696?

Answer 25

Indications:

• Reduce risk of CV death and HF hospitalization in patients with chronic HF and reduced EF
• used with other HF therapies in place of ACEI or ARB

Contraindications:
-angioedema risk with history (African Americans)

Question 26

What medication has the only effect of pure heart rate reduction?

Answer 26

Ivabradine

Question 27

What are the contraindications of ivabradine?

Answer 27

• Pregnancy
• low blood pressure
• Sick sinus syndrome, AV blocks
• *Monitor for A. fib/ bradycardia
• *interacts with CYP450

Question 28

Back to beta blockers. T/F: you should start therapy by using small doses of beta blocker.

Answer 28

True.
You need to give small amounts and gradually increase dose to get your heart used to not having NE (without withdrawal-like symptoms)