49 - Drugs Influencing Cardiac Structure and Function

Question 1

What determines preload?

Answer 1

Input into the heart

Question 2

What determines afterload?

Answer 2

Resistance to flow of blood vessels after heart

Question 3

Old name for heart failure

Answer 3

Dropsy

Question 4

How was symptomatic relief of dropsy achieved?

Answer 4

Digitalis extracts from Foxglove plant

Question 5

Active component of digitalis

Answer 5

Digoxin, a cardiac glycoside

Question 6

Effect of cardiac glycosides on myocytes

Answer 6

Increases Ca2+ release in cardiac myocytes after depolarisation.
At lower doses increases contractility.
At higher doses have dysrhythmias

Question 7

Mechanism of digoxin action 
1)
2)
3)
4)

Answer 7

1) Inhibit Na+/K+ ATPase.
2) Increased intracellular [Na+] decreases Ca2+ extrusion from cell.
3) This increases [Ca2+] in sarcoplasmic reticulum
4) This increases amount of Ca2+ released on action potential

Question 8

Margin of safety of cardiac glycosides

Answer 8

Narrow margin of safety.

Question 9

Side effects of cardiac glycosides
1)
2)
3)

Answer 9

Affects all excitable tissues

1) GIT - anorexia, nausea, diarrhoea
2) CNS - drowsiness, confusion, psychosis
3) Cardiac - ventricular dysrhythmias

Question 10

What are cardiac glycosides used to treat?

Answer 10

Atrial dysrhythmias

Question 11

What increases cardiac glycoside toxicity?
1)
2)
3)

Answer 11

1) Low K+
2) High Ca2+
3) Renal impairment

Question 12

Why does low K+ increase cardiac glycoside toxicity?

Answer 12

K+ normally competes with digoxin for binding to Na+/K+ATPase. If there is less K+ competing, more of administered digoxin binds ATPase, increasing potency.

Question 13

Half life of digoxin

Answer 13

T1/2+~40 hours

Question 14

Volume of distribution of digoxin

Answer 14

Vd + ~400L.

Due to high-affinity binding to skeletal and cardiac muscle

Question 15

Why is digoxin used to treat atrial dysrhythmia?

Answer 15

Increases parasympathetic activity on heart, which is good for dysrhythmias from sympathetic overstimulation.
Mechanism is not well understood

Question 16

Use of beta-adrenoceptor agonists in treating heart failure

Answer 16

Intravenous, short-term treatment for acute heart failure.

Question 17

Short-term treatments for acute cardiac failure

Answer 17

Beta-adrenoceptor agonists, phosphodiesterase inhibitors

Question 18

Example of a selective beta1 adrR agonist

Answer 18

Dobutamine

Question 19

Why can’t beta1 adrR agonists be used as a long-term treatment for cardiac failure?
1)
2)
3)

Answer 19

1) Chronic activation of beta1 adrR
2) With overstimulation of beta1 from sympathetic compensation for cardiac failure, plus beta1 agonist stimulation reduced beta1 expression and coupling to signal transducers in cell.
3) Reduced sensitivity of heart to beta1 agonists or sympathetic drive

Question 20

Phosphodiesterase inhibitor use

Answer 20

Phosphodiesterase breaks down cAMP.
cAMP formed as a result of adrenoceptor stimulation, so stopping cAMP breakdown increases effects of adrenoceptor stimulation.
Used to treat heart failure (short-term treatment)

Question 21

Side effects of phosphodiesterase inhibitors

Answer 21

Same as adrenoceptor agonists

Question 22

Example of a phosphodiesterase inhibitor

Answer 22

Amrinone

Question 23

Side effects of phosphodiesterase inhibitors, adrenoceptor agonists

Answer 23

Increased cardiac work, leading to increased O2 demand

Risk of arrhythmias

Question 24

Inotrope use in treating cardiac failure

Answer 24

Can increase contractility of cardiomyocytes.

Symptomatic relief.

Question 25

Side effects of inotropes

Answer 25

Progression of symptoms (doesn’t stop underlying cause of cardiac failure)
Cardiac remodelling is sped up (hypertrophy)

Question 26

Cause of death from heart failure

Answer 26

Insufficient CO to meet tissue needs

Question 27

Causes of acute and chronic heart failure
1)
2)
3)

Answer 27

1) Loss of contractility (loss of myocardial muscle)
2) Increased afterload (pressure overload)
3) Increased preload (increased volume)

Question 28

Potential causes of loss of myocardial muscle, leading to CF

Answer 28

Ischaemic heart disease

Cardiomyopathy

Question 29

Potential causes of increased afterload, leading to CF

Answer 29

Pressure overload from aortic stenosis, hypertension

Question 30

Potential causes of increased preload, leading to CF

Answer 30

Volume overload from valve regurgitation, shunts (septal defects)

Question 31

How can compensatory mechanisms for low CO lead to worsening CF?

Answer 31

Vasoconstriction from alpha1 adrR stimulation increases afterload (pressure)

Increased blood volume from aldosterone leads to increased preload (volume)

Question 32

Potential treatments for excessive afterload 
1)
2)
3)
4)

Answer 32

1) Vasodilators (to decrease MAP)
2) ACE inhibitors
3) AT1 antagonists (alternative to ACE inhibitors)
4) Beta-adrR antagonists

Question 33

Potential treatments for excessive preload 
1)
2)
3)
4)

Answer 33

1) Venodilators (to decrease volume of blood that heart has to pump).
2) Diuretics
3) Aldosterone receptor antagonists
4) Aquaretics (vasopressin receptor antagonists)

Question 34

Diuretics that are stronger than thiazides

Answer 34

Frusemide. Works on loop of Henle

Question 35

Example of venodilators

Answer 35

Nitrates.

Question 36

Effect of aldosterone receptor antagonists

Answer 36

Inhibits aldosterone action on cortical and distal tubules.

Question 37

What is spirolactone?

Answer 37

A K+-sparing diuretic.

Aldosterone receptor antagonist

Question 38

Monitoring required for aldosterone receptor antagonists

Answer 38

Monitor for hyperkalaemia, renal failure

Question 39

First-line therapy for afterload reduction

Answer 39

ACE inhibitors

Question 40

Effect on disease progression of ACE inhibitors

Answer 40

Delay progression

Question 41

Why do beta-adrR help in cardiac failure?

Answer 41

Counter-intuitive
Beta1 blockade used in early disease to protect against receptor downregulation.

Alpha1, beta1 blockade reduces afterload, cardiac work

Question 42

Effect of beta1 adrR in cardiac failure
1)
2)
3)

Answer 42

1) Reduces tachycardia, cardiac work
2) Inhibits renin release, therefore preload (volume)
3) Protects against adrenoceptor downregulation

Question 43

When do you use beta adrR in heart failure?

Answer 43

Early mild to moderate chronic heart failure

Question 44

Aims of cardiac failure treatment
1)
2)
3)

Answer 44

1) Decrease cardiac work, improve function
2) Reduce signs and symptoms
3) Increase survival (one-year survival)

Question 45

Drugs affecting contractility
1)
2)

Answer 45

Inotropes

1) Acute - beta adrR antagonists, phosphodiesterase inhibitors
2) Chronic - Cardiac glycosides (EG: digoxin)

Question 46

Drugs affecting preload

Answer 46

Diuretics, venodilators, aldosterone agonists

Question 47

Drugs providing symptomatic relief

Answer 47

Inotropes (beta adrR agonists, PDE inhibitors, glycosides), diuretics, venodilators

Question 48

Drugs that reduce mortality

Answer 48

Angiotensin inhibitors, beta adrR antagonists, aldosterone antagonists

Question 49

Drugs affecting afterload

Answer 49

Angiotensin inhibitors, beta adrR antagonists