Flashcards in Adrenergic & Angiotensinogen Block in CHF Deck (28)
What effect do ACE inhibitors have on angiotensin II and bradykin?
Block angiotensin II activation by ACE (decrease)
Prevent bradykinin degradation by kinase II (increase)
What does angiotensin II do?
Angiotensin II = one of most powerful vasoconstrictors
-stimulates aldosterone/ ADH secretion
-stimulate epinephrine/ NE
(Everything to increase CO/ preload)
What does bradykinin do?
Bradykinin = one of most powerful vasodilators
-helps prevent remodeling of heart
Where are renin and angiotensinogen (precursor) secreted?
1) angiotensinogen = made in liver
2) renin = made kidney
Name the three important ACE inhibitors (hint: -pril) and rank by their general dosing
Lisinopril: once a day
Enalapril: twice a day
Captopril: 3 times a day
If you want to know if a patient can tolerate ACE inhibitors, which one should you give them?
-not as long acting so you can see if they get too hypotensive
What are the side effects of ACE inhibitors?
-cough (switch to ARB)
-hyperkalemia (lose fluid or dehydrated)
-angioedema (immune mediated)
-renal dysfunction (not absolute contraindication)
T/F: patient should take NSAIDS to help with heart failure
-affect prostaglandins and could affect kidneys
What other drugs should be avoided with ACE inhibitors?
Salt related things:
-K sparing diuretics
Which patients should not be prescribed ACE inhibitors?
-bilateral renal artery stenosis
-maybe not kidney dysfunction
What are the clinical results from using beta inhibitors? (what outcome does it reduce)
Reduce hospitalization/ death
Reduce all cause mortality
*more severe- the greater the benefit
Do we see a greater benefit from "pushing the dose" of ACE inhibitors?
No significant benefit- can use lower dose
(contrasted to beta blockers)
What are three ARBs you could prescribe? Which ones are only taken once/ day?
* once a day
What's the rational for ARB's to block the angiotensin II RECEPTOR? which specific receptor do they block?
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)
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?
increased excretion of uric acid
Why would you use a Beta blocker with someone with heart failure?
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
What are the different sympathetic receptors and where are they?
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
What are the different classes of Beta blockers and what do they do?
Generation 1: non-selective for B1/ B2- no ancillary
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"
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?
Which are the only beta blockers proven to help with heart failure
What patient is an appropriate candidate for beta blockers?
-mild to moderate symptoms of heart failure (NYHA II-IV)
-Systolic dysfxn of LV
What are the positive clinical outcomes of beta blockers?
Improve ejection fraction
reduce mortality/ morbidity (push the dose!)
keep you out of hospital
LCZ696 is a combination of two drugs. Which ones?
ARB (valsartan) + neprolysin inhibitor
What is the function of LCZ696 (sacubitril/valsartan)?
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)
What are the indications/ contraindications of LCZ696?
-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
-angioedema risk with history (African Americans)
What medication has the only effect of pure heart rate reduction?
What are the contraindications of ivabradine?
-low blood pressure
-Sick sinus syndrome, AV blocks
**Monitor for A. fib/ bradycardia
**interacts with CYP450