CHF drugs

Question 1

In the simplest terms what is heart failure?

Answer 1

Cardiac output is inadequate to provide the oxygen needed in the body
–decrease in cardiac output results from a decline in stroke volume that is due to systolic failure, diastolic failure or a combo of both

Question 2

What is systolic HF?

Answer 2

Both the mechanical pumping action (Contractility) and ejection fraction of the heart are reduced
–typical of acute failure, esp following an MI

Question 3

What is diastolic HF?

Answer 3

Stiffening of the heart muscles and loss adequate relaxation leads to abnormal ventricular filling
–stiffening due to ventricular hypertrophy

Question 4

According to the American Heart Association, what stage do you get symptomatic heart failure?

Answer 4

Stage C

• -structural heart disease, dyspnea, and fatigue, impaired exercise tolerance
• -stage D is end stage heart failure

Question 5

Each card will go through cardiac performance, which is based on 4 primary factors. The first is preload, what is preload and how is it changed in HF?

Answer 5

Force stretching the ventricles
–increased in HF bc of increased blood volume and venous tone.
–increased ventricle stretching — increases the preload —increases force of contraction
Preload can be too high and result in pulmonary congestion due to volume overload, therefore stroke volume decreases

Question 6

The second primary factor of cardiac performance is afterload, what is this and how is it changed by HF?

Answer 6

Force which ventricles must act against
–dependent on vascular resistance
As cardiac output falls in HF, an increase in vascular peripheral resistance occurs

Question 7

The third primary factor of cardiac performance is contractility, what is this and how is it changed by HF?

Answer 7

positive inotropic agents are capable of producing some increase in contractility

Question 8

The fourth primary factor of cardiac performance is Heart Rate, what is this and how is it changed by HF?

Answer 8

As the heart fails and stroke volume diminished

–increase in heart rate occurs due to activation of B1

Question 9

Explain cardiac remodeling

Answer 9

Response of the heart to sustained decrease in cardiac output — myocardial hypertrophy occurs
—this increase in muscle mass helps maintain cardiac performance
–overtime hypertrophy leads to ischemic changes, impairment of diastolic filling, and alterations in ventricular geometry.
Remolding therefore is just slow changes in the heart due to a stressed myocardium

Question 10

There are compensatory responses that occur during HF, which involves what two mechanisms?

Answer 10

1. Sympathetic Nervous System: activation of B1 to increase HR and contractility and alpha 1 to increase peripheral resistance and vasoconstriction
2. Renin Angiotensin-Aldosterone System: decrease cardiac output = decrease in blood to kidneys= activation of renin release = increase in peripheral vascular resistance and Na/H20 retention
   - -also increased ADH and ANP release

Question 11

What is the net effect of these compensatory responses in heart failure?

Answer 11

Vasoconstriction 
Cardiac Stimulation 
Increased Blood Volume 
--try to maintain cardiac output 
--however they are responsible for the symptoms of HF and contribute to the progression of the disease.

Question 12

What is inotropy, chronotropy, dromotropy, and lusitropy?

Answer 12

Positive Inotropy: increase in cardiac contractility
Positive Chronotropy: increase in heart rate
Positive dromotropy: increase in conduction velocity
Positive lusitropy: increase in rate of relaxation

Question 13

What are the goals of treatment in HF?

Answer 13

1. Reducing symptoms and slowing progression as much as possible during stable periods
2. Managing acute episodes of decompensated failure

Question 14

What drugs are the mainstays in long term treatment of HF?

Answer 14

Reduction in ventricular wall stress
Inhibition of the renin system (ACEI, vasodilator, of Aldosterone Antagonist) or SNS (B-blocker)
–this can decrease cardiac remodeling, attenuate disease progression and decrease morbidity.

Question 15

What are ideal drugs for systolic heart failure?

Answer 15

Increase in stroke volume and reduction in preload and afterload

• -there is a loss of contractility due to dilated ventricles leading to a decreased stroke volume –leading to a low ejection fraction
• -preload is increased due to compensatory increases in blood volume

Question 16

What are ideal drugs for diastolic heart failure?

Answer 16

Impaired ventricular filling caused by hypertrophied ventricles or by impaired ventricular relaxation

1. Diuretics: treat pulmonary edema
2. Calcium channel blockers: improve ventricular relaxation and reduce heart rate (do not use in systolic heart failure due to inotropy and stroke volume reduction)
3. Beta-blockers: similar beneficial effects as calcium channel blockers
   - -positive inotropes are not used due to the fact that increasing inotropes can lead to increased outflow obstruction

Question 17

In general what are the drugs used in heart failure?

Answer 17

1. Diuretics (reduce blood volume)
2. Vasodilators (reduce peripheral resistance)
3. Cardioinhibitory drugs (Reduce heart rate and contractility)
4. Inotropic drugs (stimulate contractility)
5. Inotropic Agents used in acute cardiac failure

Question 18

These next cards will go through the stage of heart failure and the recommended drugs. Stage A (high risk for developing heart failure)

Answer 18

Goals: identifying and modifying risk factors to prevent structural heart disease and HF. Treat hypertension and lipid disorders, encourage lifestyle modifications
Routine Drugs: none
Drugs: ACEI/ARB for antihypertensive therapy
Devices: none

Question 19

Stage B ( Asymptomatic heart failure), what are the goals and drugs?

Answer 19

Goals: Minimizing additional injury and preventing or slowing remolding process
Drugs: none
Drugs for patient: ACEI or ARB and Beta Blocker if previous MI or reduced ejection fraction
Devices for selected patients: defibrillators

Question 20

Stage C ( Symptomatic heart failure), what are the goals, and drugs?

Answer 20

Goals: Minimizing additional injury and preventing or slowing remolding process
Drugs: Diuretics, ACEI and Beta-Blockers
Drugs for patients: if symptoms do not improve add: aldosterone antagonist, ARB, digoxin and/or hydralazine/isosorbide dinitrate
Devices for patients: biventricular pacing, implantable defibrillators

Question 21

Finally stage D ( refractory end stage heart failure), what are the goals and drugs ?

Answer 21

Goals: appropriate measures under stages a,b, & c.
–Should be considered for specialized therapies, including mechanical circulatory support, continuous IV positive inotropic therapy, cardiac transplantation or hospice care.

Question 22

Starting with the recommended drugs is Diuretics. They are recommended in all HF patients with evidence of fluid retention. What diuretics are used?

Answer 22

Thiazide Diuretics (hydrochlorothiazide)
--weak diuretics and re used alone infrequently with HF. Chosen over loop diuretics in patients with mild fluid retention and elevated BP 
Loop Diuretics (furosemide)
--necessary to restore and maintain euvolemia in HF. Maintain their effectiveness in the presence of impaired renal function 
Aldosterone Antagonists (spironolactone): diuretic effects are small, used instead for their beneficial effects (attenuation of cardiac fibrosis and remodeling)

Question 23

What is the primary use for diuretics in heart failure?

Answer 23

Reduce pulmonary and/or systemic congestion and edema and associated clinical symptoms
–reduce venous pressure and ventricular preload

Question 24

Next drugs used in heart failure are vasodilators. First up are the inhibitors of Angiotensin, ACEI, how does this drug help heart failure?

Answer 24

Reduce peripheral resistance therefore reduce afterload and preload
Reduce Aldosterone secretion therefore reduce Na and H20 retention
-All stages of HF should receive ACEI

Question 25

The next inhibitor of Angiotensin are ARBs (candesartan and valsartan), how does this drug help heart failure?

Answer 25

Only use ARBs in patients with A,B,C HF who are intolerant to ACEI
–ARBs may still be considered in patients who remain symptomatic despite conventional therapy

Question 26

The last inhibitor of Angiotensin are Renin Inhibitors, how does this help with heart failure?

Answer 26

Aliskiren

–efficacy similar to that of ACE inhibitors

Question 27

Moving on to the direct vasodilators, Hydralazine and Isosorbide Dinitrate, what is their clinical application?

Answer 27

Given together: Shown to help African American with moderately severe to severe HF
–need to add to the standard therapy
Can also be first line in patients unable to tolerate ACE inhibitors or ARBs due to renal insufficiency or hyperkalemia

Question 28

What is the MOA in Hydralazine and Isosorbide Dinitrate/

Answer 28

These drugs are combined orally due to complementary hemodynamic actions

• -nitrate is a vasodilator therefore reduce preload
• -hydralazine is a vasodilator that acts on arterial smooth muscle to reduce peripheral vascular resistance and increase stroke volume and cardiac output

Question 29

What are the adverse effects of this direct vasodilator combined therapy?

Answer 29

Hypotension

Reflex tachycardia and Na/H20 retention

Question 30

Moving on to the cardioinhibitory drugs, the first are the beta blockers, Carvedilol and Metoprolol. What is the clinical application of these drugs?

Answer 30

Tx of HTN, Angina, MI, Arrhythmias, and HF
HF: use beta blockers in all stable patients with HF as well as stage B patients
Diastolic Failure: number of beneficial factors including slowing heart rate, reducing myocardial oxygen demand and reducing blood pressure

Question 31

What is the MOA of Carvedilol and Metoprolol?

Answer 31

B-blockers block excessive, chronic sympathetic influences on the heart

Question 32

What are the adverse effects and contraindications in Carvedilol and Metorprolol?

Answer 32

Withdrawal effects: unstable angina, MI or even death
CVS effects: bradycardia, reduced exercise capacity, heart failure, hypotension, AV block
–if given with a calcium channel blockers this can lead to negative inotropic effects
Disturbed lipid metabolism
Hypoglycemia
Bronchoconstriction
CNS effects
Contraindiications:
Reactive airway disease, patients with sinus bradycardia or AV block