39 - Drugs Affecting Heart Rate, Dysrrhythmias

Question 1

Parasympathetic targets on the heart

Answer 1

SA node, AV node

Question 2

Receptors on heart for parasympathetic nervous system

Answer 2

ACh muscarinic receptors

Question 3

Heart response to parasympathetic stimulation

Answer 3

Bradycardia

Question 4

How is it proven that there is a tonic level of sympathetic and parasympathetic stimulation of the heart?

Answer 4

Antagonising parasympathetic (atropine) or sympathetic (atenolol) causes increase or decrease in heart rate, respectively.

Question 5

Parts of heart innervated by sympathetic nervous system

Answer 5

SA node, conducting tissue, myocardial cells

Question 6

Receptors on heart for sympathetic stimulation

Answer 6

Beta adrenoceptors, stimulated by noradrenaline, or circulating adrenaline

Question 7

Response to sympathetic stimulation of heart

Answer 7

Increase heart rate, increase force of contraction

Question 8

Effect of ACh on the heart

Answer 8

Reduces heart rate

Question 9

Does antagonising parasympathetic or sympathetic innervation have more effect on heart rate?

Answer 9

Parasympathetic

Question 10

SA node pacemaker lowest membrane potential

Answer 10

-60mV

Question 11

Phases of SA node depolarisation 1) 2) 3)

Answer 11

1) Phase 0 - Depolarisation. Ca2+ enters cell 2) Phase 3 - Repolarisation. K+ exits cell 3) Phase 4 - Spontaneous depolarisation. Na+, Ca2+ enter cell

Question 12

Membrane channels responsible for phase 4 of Sa node depolarisation 1) 2)

Answer 12

1) If Na+ channel. Leak channel. 2) Ica. Calcium channel

Question 13

Membrane channels responsible for phase 0 of SA node depolarisation

Answer 13

Ca2+ channels

Question 14

Membrane channels responsible for phase 3 of SA node depolarisation

Answer 14

K+ channels

Question 15

*Shape of SA node depolarisation

Answer 15

Question 16

How does parasympathetic stimulation slow heart rate 1) 2) 3) 4) 5)

Answer 16

1) Muscarinic M2 receptors stimulated 2) G-protein attached to M2 decreases cAMP levels, leads to K+ channel opening. 3) Na+, Ca2+ channel fluxes slowed 4) Slowed phase 4, as slower to reach threshold for depolarisation. 5) Rate of conduction through heart is also slowed

Question 17

How does sympathetic stimulation increase heart rate? 1) 2) 3) 4)

Answer 17

1) NA stimulates beta-adrenoceptor. 2) G-protein attached to adrenoceptor increases cellular cAMP, increasing Ca2+ channel opening 3) Increases slope of phase 4 in SA, AV nodes. 4) This causes increased firing (SA node), increased conduction time (AV node)

Question 18

Potential side effect of sympathetic stimulation of heart

Answer 18

Dysrrhythmias

Question 19

Resting ventricular membrane action potential

Answer 19

-90mV

Question 20

Ventricular depolarisation 1) 2) 3) 4) 5)

Answer 20

1) Phase 0 - Depolarisation, Na+ into cell 2) Phase 1 - Rapid repolarisation, K+ out of cell 3) Phase 2 - Plateau, Ca+ into cell, K+ out 4) Phase 3 - Repolarisation, K+ out of cell 5) Phase 4 - Stable membrane potential at -90mV

Question 21

*Shape of ventricular action potential

Answer 21

Question 22

How are dysrrhythmias often detected?

Answer 22

Particularly forceful heart beat after missed beat

Question 23

Symptoms of dysrrhythmias

Answer 23

Shortness of breath, fainting, fatigue, chest pain

Question 24

How to properly diagnose dysrrhythmias

Answer 24

ECG. Look at rhythm (flutter, fibrillation), rate (bradycardia, tachycardia)

Question 25

Mechanisms underlying dysrrhythmias 1) 2) 3)

Answer 25

1) Altered impulse formation. 2) Altered impulse conduction 3) Triggered activity.

Question 26

Altered impulse formation 1) 2)

Answer 26

1) Abnormal generation of action potentials at sites other than SA node. 2) Impaired SA node action potential generation.

Question 27

Altered impulse conduction 1) 2)

Answer 27

1) Conduction block - Failure to conduct action potential from atria to ventricles. Ventricles begin beating at own rate (~40bpm) 2) Re-entry - Extra beats from ventricles increase heart rate

Question 28

Triggered activity

Answer 28

Early or late ventricular depolarisation after atrial depolarisation. If too much sympathetic stimulation, can result in depolarisation when cells are meant to be refractory

Question 29

Four major classes of anti-dysrrhythmics

Answer 29

1) Na+ channel blockers 2) Beta-adrenoceptor antagonism 3) K+ channel blockade 4) Ca2+ channel blockade

Question 30

Subtypes of Type 1 anti-dysrrhythmics 1) 2) 3)

Answer 30

1) Type 1a- Moderate block 2) Type 2a- Strong block 3) Type 3a- Weak block

Question 31

Effect of type 1 anti-dysrrhythmics

Answer 31

Na+ channel blockade Reduce phase 0 slope and peak of ventricular action potential. Can alter effective refractory period

Question 32

Effect of type 2 anti-dysrrhythmics

Answer 32

Beta adrenoceptor antagonism Decrease heart rate and conduction (SA node)

Question 33

Effect of type 3 anti-dysrrhythmics

Answer 33

Delay phase 3 of ventricular action potential.

Question 34

Effect of type 4 anti-dysrrhythmics

Answer 34

Ca2+ channel blockade. Most effective at SA and AV nodes. Reduce heart rate, contractility

Question 35

Effect of type 1 anti-dysrrhythmic subtypes on effective refractory period 1) 2) 3)

Answer 35

1) Type 1a can increase effective refractory period 2) Type 1b decreases ERP 3) Type 1c has no effect on ERP

Question 36

Lignocaine

Answer 36

Anaesthetic, anti-arrythmic.

Question 37

Lignocaine effective dose for anti-arrhythmic activity

Answer 37

2-3ug/mL.

Question 38

When is lignocaine used as an anti-arrythmic

Answer 38

Given as an IV in emergencies when need to restore heart rate quickly

Question 39

How do class 2 anti-arrhythmics work?

Answer 39

Block sympathetic activity on SA and AV nodes (blockades adrenoceptors). Membrane stabilising in Purkinje fibres (inhibits Na+ channels, makes it harder to depolarise)

Question 40

Adverse effects of class 2 drugs

Answer 40

– Bradycardia, reduced exercise capacity, hypotension, AV conduction block – Bronchoconstriction, hypoglycaemia

Question 41

How do class 3 drugs work?

Answer 41

Prolong cardiac action potential by inhibiting K+ channels Slows phase 3 repolarisation. Decreases incidence of re-entry, but increases risk of triggered events

Question 42

How do class 4 drugs work?

Answer 42

Cardioselective Ca2+ channel blockers. Act preferentially on SA, AV nodes. Slow conduction velocity, increase refractoriness

Question 43

Side effects of type 4 drugs

Answer 43

Facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea