Flashcards in Cardiovascular Pharm II Deck (70):
What is heart failure associated with?
What does the decreased contractility in heart failure ultimately do
Tissues cant get enough O2 bc blood not pumping enough, this causing a sympathetic compensation
What things does the sympathetic system do to compensate for heart failure?
Increase arteriolar constriction (afterload)
Increase blood volume (preload)
Increase heart rate
Sympathetic compensation of heart failure: arteriolar constriction
Increases TPR-vascular resistance-increased afterload
-now heart has to constrict even harder against arterioles
-TX: want to decrease afterload so heart wont have to work as hard
Sympathetic compensation of heart failure: increased blood volume
-increased blood pressure
-this is a problem because the heart is already failing and now has to pump extra fluid around
-problem at the level of the veins
-preload increased (increased, end diastolic and increased venous return, all mean the same things)
-TX: want to decrease preload with diuretics or venodilate
Sympathetic compensation for Heart failure: increased HR
-leads to arrhythmia
-control this by decreasing HR
-do this with B1 blocker in low dose, because B1 blockers reduce HR AND contractility, and you do not want to decrease contractility in an already failing heart
Why do we use low does beta blocker in heart failure
Because it will Lower the heart rate without affecting contractility. If you give a higher does of B blocker, it could lower contractility, and we dont want that in an already failing heart
How does the heart compensate during failure?
-increased SANS activity
What do all of the compensatory actions of the heart during heart failure lead to
What is the main target when trying to combat cardiac remodeling in cardiac failure
-epi and NE are potential targets too, but aldosterone main one
If you something decreases remodeling, what else does it do
If something increases survival, what else does it do
What is the main goal when treating someone with heart failure
Why is there an increase in heart failure today
Because more people are surviving heart attacks and are left with failing hearts instead of dying right away
A Note Card- by Champ
What are the drugs used to treat CHF
1. RAAS inhibitors
2. B blockers
4. Inotripic drugs
5. Other vasodilators
6. If channel blocker
1-3 are the first line drugs, the others are back up
What are the type 3 drugs we use to treat CHF
1. RAAS inhibitor (ACEI or ARB, ACEI first)
2. B blocker (metoprolol)
3. Diuretics (loops and thiazides)
What is the very first drug usually given in CHF
What is the second drug usuallygiven for CHF
Why do we not give inotropic drug first for CHF?
Digoxin is very dangerous, and it’s the best option of them all. Don’t want to risk this with patients
What do diuretics do in CHF
What do ionotropic drugs do for CHF
What is the only inotropic drug that is ok for chronic use
What are the two inotropic drugs that are for acute only when treating CHF?
Phosphodiesterase inhibitors (inamrinone)
What are some other vasodilator that can be used for CHF treatment but are not first choice
-Neprilysin inhibitor (sacubitril)
What is considered first line therapy for CHF?
ACEI (and ARB but mostly ACEI)
Mechanism of ACEI in treating CHF
-inhibit the vasoconstriction effects of ANGII
-inhibit the retention of sodium and water by inhibiting aldosterone
-prevent aldosterone-mediated cardiac remodeling
Cardiovascular actions of ACEI in CHF
Preload is reduced
Afterload is reduced
Reduce the long term remodeling and therefore INCREASES SURVIVAL
What is the B blocker that is most commonly used for CHF
Clinical use of metoprolol for CHF
-In combination with ACEI (+/- diuretics, +/- digoxin)
-decreasing mortality (INCREASED SURVIVIAL)
Dosage of B blockers for CHF
Dosing is critical
-start with low dose and titration upwards
-high doses could be lethal
-if low does is not enough, you must supplement with another drug as opposed to increasing the dose
Other than decreasing HR, what other way can a low does B blocker be beneficial to a patient with CHF?
Blocks B1 on the kidneys, reducing renin
MOA of diuretics in CHF
Good at lowering fluid
What diuretics are good at decreasing fluid for CHF?
What do furosemide and HCTZ do for cardiac remodeling in CHF?
These only work to decrease fluid
What diuretics are good at reducing adolsterone in CHF?
Spironolactone and eplerenone
What is the primary use of spironolactone and eplerenone?
Decrease aldosterone to decrease remodeling to increase survival
They are not very good diuretics when it comes to decreasing fluid and decreasing preload
What is the difference in the diuretics: furosemide and HCTZ vs spironolactone and eplerenone?
Furosemide and HCTZ are good diuretics at decreasing fluid and therefore decreasing preload
spironolactone and eplerenone are good at decreasing aldosterone to decrease remodeling to increase survival! They are not good diuretics when it comes to decreased fluid
What is the neprilysin inhibitor used for CHF
An enzyme that degrades atrial and brain natriuretic peptide, two blood pressure-lowering peptides that worl mainly by reducing blood volume
What does sacubitril (a neprilysin inhibitor) do
-Inhibits neprilysin (increase ANP and BNP levels)
-increases levels of bradykinin
What is an ARNI
Sacubitril + Valsartan
Angiotensin II receptor blocker neprilysin inhibitor
How do you take sacubitril?
You take it in combination with valsartan, called ARNI together
Adverse effects of sacubitrol
Cough and angioedema, due to the increased bradykinin
What is ivabradine
If (funny) sodium channel blocker
What is the If channel responsible for
The automaticity of the SA node; these channels are unregulated in heart failure patients
How does ivabradine (If channel blocker) work
-Decreasing the diastolic depolarization slope in the SA node, decreasing heart rate without direct effects on contractility
-used for patients in sinus rhythm with resting HR >70bpm and also taking B blockers at their highest tolerable dose
Ivabradine is used with what other drug
If sodium channel blockers on HR and contractility
Decreases HR and does nothing to contractility
Does ivabradine replace B blockers?
Use WITH B blockers
CCB for heart failure
Pretty much don’t use them much but it is a last resort option
-provide no mortality benefit
-Derived from the plant digitalis (foxglove)
-increase contractility of heart (positive inotropic effect)
Therapeutic index of digoxin
MOA of digoxin (inotropic drug)
Reversible binds to the Na+-K+ ATPase of cardiac cells
How does digoxin cause increased contractiltiy ?
-Digoxin binds and inhibits Na+-K+ ATPase
-increases intracellular Na+
-increased intracellular Na leads to a greater Ca++ incflux
-Ca++ stored in SR
-more Ca++ now released when heart contracts, causing stronger contractility
When is digoxin contraindicated?
In patients with hypokalemia
Why is digoxin contraindicated in patients with hypokalemia?
Digoxin binds to the same site as the K+ on the Na+-K+ ATPase, competing.
-hypokalemia leads to more digoxin being able to bind
-huge problem leading to digoxin toxicity
When do you use digoxin?
When you cant control heart failure with the first three choice drugs
What are the adverse effects of digoxin?
Nausea, vomiting, confusion, and blurred vision (CNS EFFECTS!)
What drug is someone proanbably on if they complain of yellowish halos and blurred vision?
Factors predisposing to digitalis toxicity
What drugs should be avoided when taking digoxin
Diuretics, they can be potassium wasting and cause digoxin toxicity
What drugs are only used for acute settings of heart failure, such as in the hospital
B agonists and congestive heart failure
Positive inotropic effects, but used only short term due to tachypylaxis (rapid tolerance)
What is the B agonist we use for acutely for heart failure
-actions on B1 receptors and enhances cardiac contractiltiy
Phosphodiesterase inhibitors and heart failure
-Only in hospital (acute)
-mortality with long term use
How does phosphodiesterase inhibitor work?
B receptors stimulation causes production of cAMP, which causes protein kinase A increase, which phosphorylation the Ca2+ channel to open it
Phosphodiesterase inhibitors stop the PDEIII from breaking down cAMP, so that it can open more Ca2+ channels
Only want to do this short term
Opposite of a B blocker
How does a B agonist increase contractility?
Increase of Ca++ into the cell, goes to SR, more Ca++ released for contraction
What is the phosphodiesterase inhibitor we use for heart failure