Drugs for Heart Failure

Question 1

Give the 9 drug classes / drugs that are used for heart failure

Answer 1

1. ACE-Is / ARBs
2. Beta blockers
3. Loop diuretics
4. Sacubitril-Valsartan
5. Mineralocorticoid receptor antagonists
6. Nitrates
7. Hydralazine
8. Ivabradine
9. Cardiac glycosides (digitalis)

Question 2

Name 4 beta blockers that can be used to treat heart failure and state their cardioselectivity

Answer 2

1. Carvedilol: Non selective
2. Bisoprolol: Beta-1 selective
3. Metoprolol XL: Beta-1 selective
4. Nebivolol: Mixed selectivity

Question 3

Give 3 other features of carvedilol use besides its use in hypertension and heart failure

Answer 3

1. Can bind to alpha-1 receptors to reduce peripheral vascular resistance
2. Antioxidative
3. Anti-ischaemic

Question 4

Name the natriuretic peptide that increases with heart failure

Answer 4

Brain natriuretic peptide (BNP)

Question 5

Give 4 effects of BNP

Answer 5

1. Promotes vasodilation
2. Promotes natriuresis
3. Promotes diuresis
4. Antagonises RAAS which has favourable effects on heart failure

Question 6

Name the enzyme that breaks down NPs

Answer 6

Neprilysin

Question 7

Name 3 molecules that are broken down by neprilysin

Answer 7

1. Natriuretic peptides eg BNP
2. Angiotensin II
3. Bradykinin

Question 8

Intended MOA of sacubitril

Answer 8

Inhibits neprilysin leading to prolonged BNP effects which is good for HF

Question 9

Why must valsartan be given with sacubitril?

Answer 9

Since neprilysin also breaks down Ang II, valsartan is given to act as an Ang II blocker which can reduce the side effects of prolonged Ang II, which is bad for HF

Question 10

Sacubitril-Valsartan is known as an ___ inhibitor

Answer 10

ARNi: Angiotensin receptor/neprilysin inhibitor

Question 11

Clinical use of sacubitril-valsartan

Answer 11

Heart failure with reduced ejection fraction (HFrEF)
*Can replace ARB / ACEIs

Question 12

State 5 ADRs of sacubitril-valsartan use

Answer 12

1. Hypotension
2. Hyperkalemia
3. Dry cough (due to increase in bradykinin)
4. Renal failure
5. Angioedema

Question 13

Name 3 loop diuretics

Answer 13

1. Furosemide
2. Bumetanide
3. Ethacrynic acid

Question 14

Describe MOA of loop diuretics

Answer 14

Inhibit the luminal Na+/K+/2Cl- ion transporter in the thick ascending limb of the loop of Henle.
This increases the excretion of Mg2+ and Ca2+ (loss of lumen positive electric potential that decreases reabsorption of cations)

Also induces renal PG synthesis and increases renal blood flow (furosemide)

Question 15

____ interfere with the actions of loop diuretics by ____ PG synthesis

Answer 15

NSAIDs (eg aspirin)
Reducing

Question 16

State 4 clinical uses of loop diuretics

Answer 16

1. Acute pulmonary oedema and other edema
2. Acute hyperkalemia
3. Acute renal failure
4. Anion overdose: toxic ingestions of bromide, fluoride, iodide

Question 17

State 4 ADRs of loop diuretic use

Answer 17

1. Hypokalemic metabolic alkalosis
2. Ototoxicity
3. Hyperuricemia
4. Hypomagnesemia

Question 18

Loop diuretics should not be given together with ____ antibiotics (due to increased risk of ototoxicity)

Answer 18

Aminoglycosides

Question 19

Where in the nephron do mineralocorticoids primarily work at

Answer 19

Collecting duct cells (specifically principal cells)

Question 20

Name 4 potassium-sparing diuretics (mineralocorticoid receptor antagonists)

Answer 20

1. Spironolactone
2. Eplerenone
3. Triamterene
4. Amiloride

Question 21

MOA of spironolactone and eplerenone

Answer 21

Binds and blocks the aldosterone receptor

Question 22

MOA of triamterene and amiloride

Answer 22

Binds and blocks the sodium channel

Question 23

2 clinical uses of potassium-sparing diuretics

Answer 23

1. Diuretic
2. Hyperaldosteronism

Question 24

Does spironolactone have a slow or fast onset of action?

Answer 24

Slow

Question 25

Triamterene is metabolised in the ___

Answer 25

Liver

Question 26

Compared to amiloride, triamterene has a shorter or longer half-life?

Answer 26

Shorter

Question 27

State 5 ADRs of potassium-sparing diuretic use

Answer 27

1. Hyperkalemia 2. Metabolic acidosis 3. Gynacomastia (spironolactone use) 4. Acute renal failure (triamterene with indomethacin) 5. Kidney stones (triamterene)

Question 28

Name a potassium-sparing diuretic associated with gynaecomastia

Answer 28

Spironolactone

Question 29

Name a potassium sparing diuretic associated with acute renal failure and kidney stones

Answer 29

Triamterene

Question 30

Name an NSAID when used with triamterene that increases the risk of acute renal failure

Answer 30

Indomethacin

Question 31

MOA of hydralazine

Answer 31

Direct arteriole vasodilator. Inhibits the inositol triphosphate (IP3) induced release of calcium from the smooth muscle sarcoplasmic reticulum. This reduces peripheral resistance causing compensatory release of NE and E leading to increased venous return and cardiac output

Question 32

2 clinical uses for hydralazine

Answer 32

1. HFrEF 2. Acute onset severe peripartum and postpartum hypertension

Question 33

Route of administration of hydralazine for HFrEF

Answer 33

Oral

Question 34

Route of administration of hydralazine for acute onset severe peri and postpartum HTN

Answer 34

IV

Question 35

In treating HFrEF with hydralazine, combination therapy with ____ should be used.

Answer 35

Isosorbide dinitrate (ISDN)

Question 36

Hydralazine is a good second line medication for what condition?

Answer 36

Hypertension

Question 37

2 ADRs of hydralazine use

Answer 37

1. Baroreflex associated sympathetic activation symptoms: Flushing, hypotension, tachycardia 2. Hydralazine-induced lupus syndrome (HILS)

Question 38

State 4 clinical presentations of hydralazine induced lupus syndrome (HILS)

Answer 38

1. Arthralgia 2. Myalgia 3. Serositis 4. Fever

Question 39

Treatment for HILS

Answer 39

Discontinue hydralazine therapy

Question 40

Hydralazine is contraindicated in patients with

Answer 40

Coronary artery disease (because hydralazine stimulates sympathetic nervous system causing increased CO / O2 demand, thus causing myocardial ischaemia)

Question 41

Name 2 forms of digitalis (which are cardiac glycosides)

Answer 41

1. Digoxin 2. Digitoxin

Question 42

Route of administration of digitoxin and digoxin

Answer 42

Oral

Question 43

Digitoxin is extensively metabolised in the ___ and excreted in the ___

Answer 43

Liver Feces

Question 44

Is digoxin extensively metabolised?

Answer 44

No

Question 45

Primary excretion route for digoxin

Answer 45

Unchanged by the kidney

Question 46

MOA of digitalis

Answer 46

Directly inhibits the Na+/K+ ATPase pump in the cardiac myocytes, thus increasing intracellular sodium concentration This leads to less Ca2+ efflux by the Ca2+/Na+ exchanger, leading to higher intracellular calcium concentration, causing stronger systolic contractions

Question 47

2 clinical uses of digitalis

Answer 47

1. Systolic dysfunction 2. Atrial fibrillation

Question 48

3 ADRs of digitalis use

Answer 48

1. Progressively more severe dysrhythmia: AV block, AF, VF 2. GI effects: nausea, anorexia, vomitting 3. CNS effects: fatigue, confusion, headache, blurred vision

Question 49

4 treatment for digitalis toxicity

Answer 49

1. Discontinue cardiac glycoside therapy 2. Correction of potassium or magnesium deficiency 3. Antiarrythmic drugs (if automaticity predominant, use lidocaine or propranolol) 4. Digoxin antibody (eg FAB fragments, digibind)