Drugs for Heart Failure

Question 1

What used to be the main treatment for heart failure?

Answer 1

Digitalis

Question 2

Characteristics of diastolic heart failure

Answer 2

Prevalence approx 40-60%
More common in women
Concentric remodeling
Preserved EF

Question 3

What makes DHF distinct from SHF?

Answer 3

DHF has poor tolerance of AFib
DHF has poor tolerance of tachycardia
DHF worsened by increased MAP
Can cause “flash” pulmonary edema

Question 4

What does chronic compensatory remodeling include?

Answer 4

Aortic stenosis
Chronic HTN
Valvular regurgitation

Question 5

ARB =

Answer 5

Angiotensin II receptor blockers

Question 6

Aliskiren inhibits:

Answer 6

Conversion Angiotensinogen –> Angiotensin I

Renin

Question 7

ACE inhibitors inhibits which conversion?

Answer 7

Angiotensin I –> Angiotensin II

Question 8

What does Spironolactone inhibit?

Answer 8

Aldosterone’s action at the kidneys

Question 9

What suffixes are associated with ACE inhibitors?

Answer 9

• prils

- sartans

Question 10

Less Angiotensin II leads to:

Answer 10

Less vasoconstriction - decreased afterload

Less aldosterone secretion and lass sodium/water retention - decerased preload

Decreased cell proliferation and remodeling

Question 11

Captopril MOA:

PKs (1/2 life):

Toxicities:

Answer 11

Competitively inhibit ACE

1.7 hrs.

Cough, angioedema

Question 12

Losartan MOA:

Answer 12

Non-peptide angiotensin II receptor antagonist (ARB)

Question 13

Valsartan 1/2 life

Candesartan 1/2 life

Answer 13

6-10 hrs, not a pro-drug

5-9 hrs, irreversible binding

Question 14

Which ACE inhibitors have a long half-life and allow for 1x/day dosing?

Answer 14

Benazepril

Lisinopril

Question 15

Valsartan/Sacubitril MOAs

Clinical applications:

S/E:

Answer 15

Valsartan antagonizes Angiotensin I receptors (ARB). Sacubitril inhibits neprilysin (NEP), which delays degredation of ANP.

HF, can be substituted for ACEI or ARB.

HypoTN, hyperkalemia, increased serum creatinine.

Question 16

What drug class is recommended for first-line treatment of HF?

Which patients should get these drugs?

What are containdications?

Answer 16

ACEI

All pts. w/ LV systolic failure or LV dysfunction w/o HF.

Unable to tolerate
Pregnant
HypoTN
Elevated serum creatinine
Hyperkalemia

Question 17

Carvedilol MOA

Effect:

Who should get it?

Used in tandem with?

Answer 17

Prevents down-regulation of beta-1 receptors and make them more sensitive to SNS activation.

Protects from arryhthmias, lower [renin], lower myocardial consumption, limits remodeling.

Patients who are STABLE w/ symptomatic CHF and LVEF < 40%.

ACEI

Question 18

Ivabradine MOA

Clinical applications:

Answer 18

Disrupts funny current to prolong diastole and slow HR.

Pts. w/ resting HR > 70 bpm w/ LVEF < 35% (elevated HR and low EF).

Question 19

Sprinolactone MOA

Benefits of Spironolactone:

Why is it often under-utilized?

Answer 19

Competitively inhibit Aldosterone by increasing plasma K+ and decreasing Na+ and volume.

Decrease myocardial fibrosis
Reduce morning rise in HR
Reduce mortality/morbidity

There is a fear of hyperkalemia.

Question 20

Damaged heart vasculature can synthesize what?

Answer 20

Aldosterone post MI

Question 21

Recommended restriction of salt/day

Answer 21

< 3 gm salt/day

Question 22

What does Furosemide inhibit?

What is the major toxicity?

Answer 22

Na+/K+/2Cl- cotransporter

Sulfonamide

Question 23

What diuretic is used for patients with a sulfa allergy?

Answer 23

Ethacrynic acid

Question 24

What is the 2-drug combo given to only AAs?

Answer 24

Isosorbide dinitrate (to dilate vv. and lower pre-load) and hydralazine (dilate aa. and lower afterload)

Question 25

Major toxicity of Hydralazine?

Answer 25

Drug-induce lupus

Question 26

Digoxin MOA

Benefits:

Answer 26

Competes w/ Na+/K+ ATPase to increase inotropic effect.

Increased CO

• less SNS activity
• increased urination
• reduced renin

Question 27

ECG changes w/ Digoxin at therapeutic levels:

Toxic levels:

Answer 27

Depression of ST segment and increased PR interval

AV dissociation - no relationship between P and QRS