Drugs affecting cardiac rate and force

Question 1

Dobutamine, adrenaline and noradrenaline are which kind of drug?

Answer 1

b-adrenoceptor agonists

Question 2

What are the pharmacodynamic effects of b-adrenoceptor agonists upon the heart?

Answer 2

increase force, rate, CO and O2 consumption

decrease cardiac efficiency - O2 consumption increased more than cardiac work does

Question 3

Which b-adrenoceptor agonists have a plasma half-life of approx. 2 mins?

Answer 3

adrenaline and dobutamine

Question 4

Why is adrenaline given IV in a cardiac arrest?

Answer 4

positive inotropic and chronotropic actions

redistribution of blood flow to heart (constricts peripheries)

dilatation of coronary arteries

Question 5

What is the route of administration of adrenaline in an anaphylactic shock?

Answer 5

IM (IV if enter cardiac arrest)

Question 6

What is the route of administration of dobutamine?

Answer 6

IV infusion

Question 7

In which condition would dobutamine be used?

Answer 7

acute, but potentially reversible, heart failure

Question 8

What do the physiological effects of a b-adrenoceptor blockade depend upon?

Answer 8

the degree to which the sympathetic nervous system is activated

Question 9

Which b-adrenoceptor antagonist is non-selective for b1 and b2 adrenoreceptors?

Answer 9

propranolol

Question 10

Atenolol, bisoprolol and metoprolol block which adrenoceptor in a competitive manner?

Answer 10

B1

Question 11

Which b-adrenoceptor antagonist is non-selective and a partial agonist?

Answer 11

alprenolol

Question 12

What is the effect of non-selective b-adrenoceptor antagonists during exercise?

Answer 12

force and CO are significantly depressed - reduction in maximal exercise tolerance

myocardial O2 requirement falls -> better oxygenation of the myocardium

Question 13

What are the CVS clinical used of b-adrenoceptor antagonists?

Answer 13

Arrhythmias
Angina
Heart failure
Hypertension

Question 14

How do b-blockers work in treatment of AF and SVT?

Answer 14

delay condition through the AV node and help restore sinus rhythm

Question 15

In which condition are b-blockers first line as alternative to CCBs?

Answer 15

angina

Question 16

In which CVS condition does use of b-blockers seem paradoxical?

Answer 16

heart failure - studies show that low-dose b-blockers improve morbidity and mortality

Question 17

Which b-blocker is often used in heart failure?

Answer 17

carvedilol - start low, go slow

Question 18

B-blockers are no longer first line treatment for hypertension, unless…?

Answer 18

co-morbidites (e.g. angina) are present

Question 19

What are the adverse effects of b-bockers (as a class)?

Answer 19

Bronchospasm
Aggravation of cardiac failure
Bradycardia 
Hypoglycaemia 
Fatigue
Cold extremities

Question 20

Which b-blockers have less associated risk of bronchospasm?

Answer 20

b1-selective agents e.g. atenolol, bisoprolol, metoprolol

Question 21

If b-blockers can aggravate cardiac failure, why are they used in treatment of heart failure?

Answer 21

studies show that low dose b-blockers are used in compensated heart failure - patients may be relying on sympathetic drive to maintain an adequate CO and b-blockers reduce sympathetic drive so risk of crash - start low, go slow

Question 22

Which bADR receptors are implicated in fatigue caused by b-blockers?

Answer 22

b1 - cardiac output, and b2 - skeletal muscle perfusion in exercise are regulated by adrenoceptors

Question 23

Name a non-selective competitive antagonist of muscarinic ACh receptors?

Answer 23

atropine

Question 24

What is the effect of non-selective muscarinic ACh receptor antagonists?

Answer 24

Increase HR in normal subjects
No effect on arterial BP
No effect on response to exercise

Question 25

Why is the effect of atropine different in athletes?

Answer 25

SV is larger due to greater mass of cardiac muscle Highly trained athletes have increased vagal tone Atropine effect is exaggerated since blocks greater parasympathetic drive

Question 26

What are the clinical uses of atropine?

Answer 26

First line in severe bradycardia, particularly following MI - vagal tone is elevated. Anti-cholinesterase poisoning (to reduce excessive parasympathetic activity)

Question 27

What is an alternative to atropine in severe bradycardia?

Answer 27

Glycopyrronium

Question 28

What is the name of a cardiac glycoside that increases contractility of the heart?

Answer 28

digoxin

Question 29

Drugs used in heart failure?

Answer 29

Digoxin Dobutamine b-blocker (low dose)

Question 30

What is the effect of digoxin (and other inotropes) on the Starling curve?

Answer 30

Shift upwards and left on the function curve, such that SV increases at any given EDP

Question 31

In heart failure, how is the Starling curve changed?

Answer 31

depressed and shifted right - cardiac contractility is reduced

Question 32

How does digoxin increase contractility of the heart?

Answer 32

``` blocks the sarcolemma Na/K-ATPase: Increase intracellular Na Increase intracellular Ca Increase Ca storage in SR Increase CICR and therefore, contractility ```

Question 33

Which subunit on the Na/K-ATPase does digoxin bind to?

Answer 33

alpha subunit in competition with K+

Question 34

What can dangerously enhance the effects of digoxin?

Answer 34

low plasma K+ concentration (hypokalaemia)

Question 35

What are the indirect actions of digoxin on electrical activity?

Answer 35

Increased vagal activity; slows SA node discharge, slows AV node conduction - increases refractory period

Question 36

What are the direct effects of digoxin on electrical activity?

Answer 36

Shortens AP and refractory period in atrial & ventricular myocytes

Question 37

What effect on the electrical activity does a toxic concentration of digoxin have?

Answer 37

membrane depolarisation and oscillatory after-potentials - likely due to Ca2+ overload

Question 38

What are the clinical signs of digoxin toxicity?

Answer 38

Nausea, vomiting, anorexia, diarrhoea. Blurred vision, yellow/green discolouration, haloes. Palpitations, syncope, dyspnoea. Confusion, delirium, fatigue

Question 39

Signs of digoxin toxicity on an ECG?

Answer 39

Down-sloping ST depression = reverse tick/sagging/scooped Flattened, inverted, or biphasic T waves Shortened QT interval

Question 40

Descrive a biphasic T wave and in which leads it would be seen.

Answer 40

initial negative deflection and terminal positive deflection V4-6 (those with a dominant R wave) First part is normally continuous with the depressed ST segment

Question 41

Why is the QT interval shortened due to digoxin toxicity?

Answer 41

it shortens the refractory period

Question 42

What are the different admin routes for Digoxin and in which scenario would they be used?

Answer 42

IV in acute heart failure | Orally in chronic heart failure

Question 43

In which arrhythmia is digoxin particularly indicated?

Answer 43

AF

Question 44

Which new drug would be useful in acute decompensated heart failure?

Answer 44

Levosimendan IV (calcium sensitiser)

Question 45

How do calcium sensitisers work?

Answer 45

Bind to troponin C in cardiac muscles sensitising it to the action of Ca2+ -> contraction Also opens K-ATP channels in vasculature -> vasodilation - reduces after load and cardiac work