Lecture 3 - Heart Failure Drugs 1 Flashcards
Define Heart Failure
an abnormality of cardiac structure or function leading to the failure of the heart to deliver oxygen at a rate that fulfills the requirements of the tissues in the body
Most patients with heart failure have what other condition?
high blood pressure
Most patients with heart failure have what characteristics about their heart?
enlarged heart muscle and chamber
look at slide 6
kay
Heart failure is defined as having an Ejection Fraction (EF) as less than ?%
less than 50%
What is the formula for EF?
EF % = amount of blood pumped out of the ventricle / total amount of blood in the ventricle
Systole = ventricles ______
contracting
Diastole = ventricles _____
relaxing
Cardiomycocytes respond to action potential by ______ of the membrane
depolarization
Starts by shortening of _____ proteins and ends with relaxation and return to resting state
contractile
Cardiomyocytes are ______ in intercalated discs that respond to stimuli as a unit
interconnected
What is an echocardiography?
- send sound waves into the body which are reflected at the interfaces between tissue
- return time tells us the depth of the reflecting surface
Force of muscle contraction is related to the amount of cytosolic ____
Ca2+
Initially, heart failure is not perceived by the patient due to ______
compensation
As failure increases, _____ mechanisms keep increasing
compensatory
*But at some point, no longer able to improve condition - decompensated HF
List some risk factors and co-morbidities that contribute to the development of HF
- age
- smoking
- obesity
- hypertension
- coronary artery
- disease
- diabetes
- dyslipidemia
What are some heart failure symptoms?
- dyspnea
- edema
- fatigue
- cough
List 3 ways that the body corrects slight decreases in blood pressure
*note this happens in early heart failure and the patient may not even be aware that they are experiencing heart failure due to the compensatory mechanisms
1) increased sodium retention (slow benefit)
- with water retention this increases blood volume
2) activation of RAAS
- angiotensin - constricts arteries/veins (fast benefit)
- aldosterone - sodium retention (slow benefit)
3) sympathetic nerve activation
- increased HR (fast benefit)
- increased contractility (fast benefit)
*pic on slide 16 explains this well :)
____ in heart failure (decompensated) these things worsen the condition
Late
How does “overly increased plasma volume and constriction of veins” worsen the condition in late heart failure?
- increased venous return stretches already overstretched ventricles
- heart no longer able to increase force of contraction
- heart size enlarges (dilates) and muscle thickens (hypertrophy)
- venous pressure increases - edema - peripheral and pulmonary
How does “overly increased constriction of arteries” worsen the condition late in heart failure?
- greatly increased peripheral resistance hard for heart to empty against
- increased resistance to outflow more than heart can now overcome
How does “cardiac overstimulation” worsen the condition late in heart failure?
- now little response - heart has failed
- overstimulation of B-adrenergic receptors
- down regulation of these receptors
- increased fibrosis
- increased apoptosis (cell death)
How do the compensatory mechanisms of early heart failure worsen the condition in late heart failure?
- Patient no longer able to compensate and overt signs of heart failure appear
- But now heart must deal with large increases in RAAS, SNS and blood volume
Describe Left Side Failure
- blood backs up into lungs and periphery
- pulmonary (edema)
- life threatening
- sitting up helps (more blood in lower veins)
*may prevent right side pumping and blood backs up into veins
Describe Right Side Failure
-blood backs up into periphery
peripheral edema
Main Symptoms of Heart Failure
- Shortness of breath
- Shortness of breath at night
- Need to sit or stand to breath easily
- Reduced exercise tolerance
- Fatigue
- Ankle swelling
- Peripheral edema
- pulmonary Edema
Main Signs of Heart Failure
- Sweating
- Increased HR
- Elevated jugular venous pressure
- Hepato-jugular reflux
- Rapid breathing
- Cardiac murmur
Clear relationship between ??
severity of symptoms and survival
Poor relationship between ??
severity of symptoms and ventricular function
*patients with mild symptoms may still have a relatively high absolute risk of hospitalization and death
Stage A heart failure vs. Stage D heart failure:
which is worse
Stage D
*slide 23
Most common cause of HF is ?
coronary artery disease
HF has a complex pathophys involving activation of 2 key neurohormonal systems: ?
- RAAS
- SNS
What are the 5 drug classes for treating HF?
1) Inhibitors of RAAS
- ACEi (enalapril)
- ARB (losartan)
2) B-adrenergic receptor blockers
- metoprolol
- carvedilol
3) Ionotropes
- digoxin
- dobutamine
4) Diuretics
- furosemide, metolazone
- aldosterone antagonist (spironolactone)
5) Others
- vasodilators (not covered in this course)
ACE inhibitors decrease formation of ??
angiotensin 2
Why would you want to decrease angiotensin 2 (by using an ACEi in HF?)
*want to decrease the compensatory mechanisms
- compensation to heart failure involves the RAAS
- in the long term, vasoconstriction and blood volume retention become a problem
Give an example of an ACE inhibitor
enalapril
What effects will ACE inhibitors cause?
1-decreased constriction in arteries and veins
-decreased preload and after load (heart works less)
2-decreased aldosterone by decreased angiotensin 2
-decreased blood volume (and decreased venous return)
3-decreased remodeling
-decreased thickening of heart tissue
___ are considered first line for HF
ACE inhibitors
When are ACEi started?
-soon after diagnosis of HF
Describe the benefits ACEi provide to patients with HF
- excellent single therapy
- improve clinical signs and symptoms
- significantly decrease morbidity and mortality
- reduces death caused by:
- progressive heart failure
- cardiac arrhythmia
- myocardial infarction
- stroke
Enalapril has many benefits including: ?
- survivial
- symptoms/QOL/exercise tolerance
- hospitalizations/ER visits
- ejection fraction and hemodynamics
*Effective in slowing the course of heart failure
____ should be the first line drug in heart failure after edema has been taken care of if present
Enalapril (ACEi)
Enalapril generally used in combo with ??
furosemide *to treat edema
Can ACEi be used in pregnancy?
NOOO
-causes birth defects (and some parents just don’t want this for their children)
ACEi can cause ____ due to aldosterone decrease (can cause abnormal heart rate and cardiac arrest)
hyperkalemia
ACEi can cause a dry ____
cough
ACEi are metabolically neutral so there will be no effect on _____ or ____ ______
lipids or blood glucose
What intervention is required when ACEi are given with spironolactone?
dose adjustments are necessary to avoid hyperkalemia
What other drugs can cause increased potassium levels (hyperkalemia) when given with enalapril?
- Ibuprofen/Indomethacin: chronic use of NSAIDs
- Losartan (ARBs)
- Alka-Seltzer (antacid)
- Trimethoprim (antibiotic)
Give an example of an ARB
Losartan
Ultimate action of ARBs is similar to ____ but without the effects of increasing _____
ACEi
bradykinin
With ARBs there will be no ____ like there is with ACEi
cough
ARBs have similar complications and drug-drug interactions to those seen with ____
ACEi
an ARB (losartan) combined with enalapril or spironolactone increases the risk of _____
hyperkalemia
Efficacy of losartan is reduced by ???
grapefruit juice
