Heart Failure Drugs

Front 1

Clinical manifestations of heart failure

Back 1

symps of intravascular and interstitial volume overload (eg, dyspnea, rales, edema) and/or inadequate tissue perfusion (eg, fatigue, poor exercise tolerance)

Front 2

Systolic heart failure defined by

Back 2

- bad pump which cannot empty efficiently i.e. heart with low ejection fraction
- or a heart with poor contractility-- i.e. has impaired wall motion, dilated ventricle, -- 2/3 b/c of coronary artery disease and 1/3 b/c of non ischemic cardiomayopathy--htn, valvular disease, alcohol, myocarditis

Front 3

Diastolic heart failure defined by

Back 3

- due to stiffness of left ventricle which results in impaired ventricular relaxation & filling. About 30-50% of heart failure. NORMAL EF (>40%). Also will have concentric hypertrophy-- b/c of htn. Slightly better mortality than systolic HF.

Front 4

What is current Tx for DIASTOLIC heart failure?

Back 4

Lack of objective data to guide therapy for pharm management of diastolic HF. 1. However Tx for systolic failure helps to reverse cardiac hypertrophy and improves LV stiffness (i.e. ace inhibi and beta blockers). 2.Control Htn which inhibs myocardial relaxation and promotes hypertrophy. 3. Tx the myocardial ischemia which impairs ventricular relaxation 4. more specifically you can decrease HR with VERAPAMIL and DILTAEZEM and beta blcokers so more time for heart to fill (DO NOT USE NONDIHYDROPYRIDINES with SYSTOLIC HF)

Front 5

Initial cardiac insult causes primary damage to cardiac function and leads to lower CO which causes body to respond by

Back 5

holding onto Na to maintain water and increases PVR so body shunts blood to most vital organs- b/c body thinks it s bleeding to death

Front 6

Name compensatory mechs employed by the heart that are initially help but will eventually lead to more hypertrophy of the heart and heart damage.

Back 6

- RAAS actvn
- increased symp tone
- frank starling phenomenon
- myocardial hypertrophy

Front 7

Reduced blood Q is sensed by kidneys and kidneys respond by activating the RAAS syst, which cells release renin? Renin leads to the actn of what protein?

Back 7

- JG cells of kidney
- Angiotensin 2

Front 8

AT 2 is powerful vasoconstrictor that has what effect on the force that the heart has to pump against? AT 2 also has what effect on myocardial cells and fibroblast proliferation?

Back 8

AT 2 increases AFTERLOAD by increasing PVR.
AT 2 DIRECTLY stimulates hypertrophy and cardiac remodeling leading to apoptosis, necrosis and arrhythmias.

Front 9

Aldosterone which is stimulated by AT 2 has what effect on the heart?

Back 9

Increases preload

Front 10

Stim of sympathetic nervous syst causes

Back 10

- more catecholamines in circulation, increase in HR, contractility, and vasoconstriction

Front 11

What is the relationship between EDV and force of contraction?

Back 11

- in any given ventricular state the force of contraction can only be increased to a limit due to increased filling pressure, after that the force of contraction will decrease--suspenders lost elasticity and force of recoil is lost

Front 12

Increased preload will eventually cause maladaptive changes via the Frank Starling mech- explain.

Back 12

- increased preload leads to increased wall tension which leads to LV dilation and then LV hypertrophy
- hypertrophy of myocytes occurs to stabilize wall tension-- which will cause fibrosis and dysrhythmias

Front 13

What is compensated heart failure and what is uncompensated heart failure?

Back 13

Compensated-- when compensatory response restores CO
Uncompensated- when bodies compensatory attempt to maintain blood Q to periphery fails to maintain CO

Front 14

What symps are seen with LHF?

Back 14

- lung symps-- cough, dyspnea, orthopnea, pulm edema, S3 GALLOP (heard in the middle of daistole after S2-- indicates blood reverberation as filling ventricles), pleural effusion

Front 15

What symps are seen with RHF?

Back 15

BI pedal edema, hepatomegaly, JVD, ascites, anorexia, abdominal bloating

Front 16

NYHA I?

Back 16

No symptoms with ordinary activity

Front 17

NYHA II?

Back 17

symptoms with ordinary activity

Front 18

NYHA III?

Back 18

marked lim with less than ordinary activity

Front 19

NYHA IV?

Back 19

symps at rest

Front 20

Stages A-D

Back 20

Stage A: High risk for HF (e.g., HTN, DM) but w/out structural heart disease or symptoms of HF
Stage B: Structural heart abnormalities of HF but w/out symptoms of HF
Stage C: Current or prior symptoms of HF w/ structural heart abnormalities
Stage D: Refractory HF requiring specialized interventions

Front 21

Diuretics generally have what type of relief? Loop diuretics act where and are most effective at what? Thiazide diuretics act as what?

Back 21

this is symptomatic relief only, have unproven benefit on mortality. diuretics should not be used as long term monotherapy, if needed for chronic therapy use LOWEST dose to maintain euvolemic state.
Loop diuretics-- act on loop of henle and are most effective at increasing sodium excretion. Thiazide diuretics -- and potassium diuretics act on distal tubules. Decrease venous pressure overload and decrease preload

Front 22

Thiazide diuretics are used for ___ fluid overload and acts synergistically with loop diuretics. Thiazides are considered useful for ___ mgmt and can prevent HF. Loop diuretics are used for ____ volume overload b.c they unload fluid faster and to a greater extent than thiazide diuretics. They also retain efficacy with reduced renal capacity.

Back 22

- thiazide useful for mild fluid and are helpful for htn mgmt.
- loop diuretics used for moderate to severe fluid overload

Front 23

Dose is whatever it takes for foresemide and can ___ the dose to a max of 400 mg

Back 23

Double--(not by increasing times per day but amt)

Front 24

Thiazide diuretics (i.e. HCTZ) should or should not be used with reduced renal fx?

Back 24

should not be used b/c are less effective if low creatinine clearance

Front 25

What to do with gut edema?

Back 25

1-2 doses of IV diuretic so subsequent oral diuretics may be better absorbed. May also give continuous IV infusion

Front 26

If there is resistance to diuretics what can be done?

Back 26

combine loop diuretic w/ other diuretic for synergy. Or increase renal blood flow via dopamine. Avoid NSAIDS and avoid xs salt intake

Front 27

Renal function is measured by ___ to assess renal perfusion.

Back 27

creatinine

Front 28

All pts with fluid overload on diuretics but ___ diuretics do not have benefit on mortality.

Back 28

Loop diuretics. Diuretics in general only provide SYMPTOMATIC relief.

Front 29

If diuretics are being used chronically what other drugs should be used?

Back 29

Add Ace Inhibitor and beta blocker (b.c there is actually increased mortality when diuretics are used as monotherapy).

Front 30

Diuretics should be taken once in morning and if it needs to be taken near night it should 4-6 hrs before bedtime to reduce night time urination

Back 30

- also should weigh daily

Front 31

Digoxin- MOA

Back 31

- slight increase in force of myocardial contraction due to increased intracell calcium and inhibition of NA/K atpase, decreases central symp outflow by sensitizing baroreceptors, and decreases renal absorption of sodium

Front 32

Digoxin- class, symptom help?, mortality?

Back 32

- positive inotropic agent
- improves symptom sof LV dysfunction-- improves exercise tolerance, and has NO effect on mortality

Front 33

Digoxin- tox

Back 33

- visual disturb, dec muscle strength, anorexia, confusion, arrhythmia, AV block, bradycardia= tox seen at greater than 2ng/ml usually. Toxicity will especially occur with HYPOKALEMIA and hypomagnesemia. Watch K+ in pts with large doses of digoxin-- maintain at 4.0 mEg/L

Front 34

Dig- has what effect on hospital admission? What effect on exercise capacity? What effect on overall survival?

Back 34

- reduces HF hospital admission
- improves exercise capacity
- no difference in overall survival

Front 35

Other inotropes besides digoxin

Back 35

Beta agonists-- dopamine, dobutamine
BNP- vasodilator, improves circulation, decreases diuretic need- expensive

Front 36

ACE INHIBITORS-- used for which classes of heart failure? MOA:

Back 36

- USED FOR ALL 4 CLASSES of SYSTOLIC dysfunction
MOA: deactivates RAAS-- dec preload, dec afterload, and dec neurohormonal stimulation

Front 37

Ace inhibition has what effect by limiting AT2 formation?

Back 37

Decreased vasoconstriction and decreases aldosterone secretion -- so decreased afterload and decreased preload

Front 38

ace innhibitors have what effect on myocardial hypertrophy?

Back 38

regression by decreasing LVH and dilatation by decreasing preload, decreases progression of adverse remodeling seen with HF

Front 39

Ace inhibitors can ___ the effects of AT 2 and NE

Back 39

- decreases cardiotoxic effects like fibrosis, apoptosis mediated by chronic AT 2 and NE

Front 40

ACE inhibitors greatly ____ mortality

Back 40

decrease

Front 41

Decrease in MI and reduced development of HF in pts given ACE inhibitors (-oprils). Should pts with Stage A HF be given ace inhibitors? Is the change in bp significant for Ace inhibitors?

Back 41

Yes
NO significant decreases in BP-- beneficial effects due to other stuff

Front 42

Ace inhibitor(-oprils)- tox

Back 42

- hypotension at initiation, dry persistent cough (due to bradykinin), check serum creatinine, BP, and K
- ace inhibitors cause renal insufficiency, hyperkalemia, angioedema

Front 43

Ace inhibitors(-oprils) -CI

Back 43

- hx of angioedema or severe rash to ace inhibitors
- pre renal azotemia
- bilateral renal stenosis
- PREGNANCY
- serum K+ > 5.5 mmol/L

Front 44

ACe inhibitors(-oprils) should be uses in all classes and provides symptomatic relief but its greatest benefit is for pts with ____ HF. There is significant underutilization of heart failure meds

Back 44

advanced

Front 45

Ace inhibitors are underused b/c of
- ___ rises in serum creatinine
- pts with____ BP
- cough

Back 45

1. small rises
2. normal BP---should aim for optimal target dose even if pts are normotensive
3. must differentiate between viral cough and ace inhibitor cough-- only stop giving if cough is intolerable-- warns pts of cough

Front 46

- symptomatic improvement via ace inhbitors may take ___

Back 46

1. wks to mos
2. ace inhibitors decreases disease progression and improve survival even if symtpoms do not respond favorably

Front 47

Arb(valsaratan) has what benefit over Ace inhibitors in terms of tox? Is arb good for pts with SE with ace inhibitors? Is valsartan good to add to beta blocker and ace inhibitor?

Back 47

- no accum of bradykinins so no cough
- yes
- no --triple therapy is not good -- increased death and hospitalization compared to when added to either med alone

Front 48

ARb- CI

Back 48

- bilateral renal stenosis
- andioedema
- preggers
- pts with K+> 5.5

Front 49

Which is better combo therapy ace inhibitor and beta blocker or ace inhib and arb?

Back 49

ace inhib and beta blocker

Front 50

Hydralazine- class, MOA (concurrent therapy?)

Back 50

- vasodilators
- directly vasodilates ARTERIAL smooth muscle-- decreases afterload, when used in combo with isosorbide dinatrate to decrease preload and afterload

Front 51

Isosorbide dinatrate- class, MOA (concurrent therapy?)

Back 51

- vasodilator
- Activation of Guanylate Cyclase-- ↑ cGMP in vascular smooth muscle
- Relaxes VENOUS smooth muscle-↓ preload
- used incombo with hydralazine which allows both preload and afterload to be reduced

Front 52

Isosorbide dinitrate and hydralazine- tox

Back 52

- more tox than ARb or ace inhibitor
- drug induced lupus (hydralazine)
- reflex tachycardia (hydralazine)
- severe hypotension if taken concurrently with phosphodiesterase inhibitor-- i.e. cialis etc

Front 53

isosorbide dintrate and hydralazine- efficacy compared to enalapril
- efficacy in AAs

Back 53

- reduction in mortality but less effective than enalapril
- increased exercise tolerance more than enalapril
- more efficacious when added to std therapy for AAs

Front 54

Isosorbide dintrate/hydralazine- use

Back 54

- side effects limit use but are alternative to arb of ace inhibitor in case of absolute CIs-- i.e. pregnany, hyperkalemia, angioedema, bilateral renal stenosis

Front 55

Beta blockers- MOA

Back 55

- blocks NE effects, decreases HR allowing more time for heart to fill and increase CO.
- also will increase heart function despite decreasing contractility-- by attenuating xs neurohormonal stim.
- helps decrease LVH and dec vent arrhythmia

Front 56

Beta blocker- effects/use

Back 56

- when used in combo- increase exercise tolerance, dec hospitilization, dec heart transplant need, and reduce heart size

Front 57

When are NON selective beta blockers used (i.e. beta blockers that will also block alpha one receptors)?

Back 57

When pt has high bp, must be careful b/c some non selective beta blockers have a much less decrease in mortality compared to selective counterparts- bucinidolol ineffective

Front 58

Beta blockers - selective, and nonselective

Back 58

- selective - metoprolol
- nonselective - carvedilol, propranolol