Session 10-Arrhythmias And CVS Drugs

Question 1

What are the causes of arrhythmias?

Answer 1

Tachycardia

Bradycardia

Question 2

What are the tachycardic causes of arrhythmias?

Answer 2

• ectopic pacemaker activity
• afterdepolarisations
• atrial fibrillation
• re-entry loop

Question 3

What are the bradycardic causes of arrhythmias?

Answer 3

• sinus bradycardia

- conduction block

Question 4

When are delayed after-depolarisations more likely to occur?

Answer 4

If intracellular Ca2+ is high

Question 5

What can early after-depolarisations lead to?

Answer 5

Oscillations

Question 6

When are early after-depolarisations likely to occur?

Answer 6

If AP is prolonged (longer AP -> longer QT)

Question 7

What can a long QT interval be due to and what can it lead to?

Answer 7

Due to iron channel abnormalities

Lead to ventricular fibrillation

Question 8

Describe how a re-entry loop can generate arrhythmia

Answer 8

• conduction block through damaged area
• incomplete conduction damage - excitation takes long route to spread wrong way through damaged area, setting up circuit of excitation

Question 9

What do multiple re-entrant circuits in the atria lead to?

Answer 9

Atrial fibrillation

Question 10

What can lead to multiple re-entry loops in the atria?

Answer 10

Mitral valve stenosis -> stretching and volume overload in atria -> damage and fibrosis and over-excitation of atria -> multiple re-entry loops

Question 11

In which ways do anti-arrhythmic drugs work?

Answer 11

• block voltage-sensitive sodium channels
• antagonists of beta-adrenoceptors
• block potassium channels
• block calcium channels

Question 12

What is an example of a drug which blocks voltage-sensitive Na+ channels?

Answer 12

Local anaesthetic lidocaine

Question 13

Describe when drugs which block voltage-sensitive Na+ channels are used

Answer 13

Only blocks channels in open or inactive state - preferentially blocks damaged depolarised tissue

Question 14

Why do drugs which block voltage-sensitive Na+ channels have little effect in normal cardiac tissue?

Answer 14

It dissociates rapidly - blocks during depolarisation but dissociates in time for next AP

Question 15

When is the only time lidocaine is used following MI?

Answer 15

If patient shows signs of ventricular tachycardia

Question 16

What does the binding of lidocaine to voltage-sensitive Na+ channels do?

Answer 16

Prevents automatic firing of depolarised ventricular tissue

Question 17

Give two examples of beta-adrenoceptor antagonists

Answer 17

Propranolol

Atenolol

Question 18

What do beta-adrenoceptor antagonists do in the heart?

Answer 18

Block sympathetic action (act at beta1-adrenoceptors in the heart)

Question 19

True or false: beta-blockers slow conduction in AV node

Answer 19

TRUE

Question 20

What effects does slowing conduction in AV node have in patients?

Answer 20

• can prevent supraventricular tachycardias

- slows ventricular rate in patients with AF

Question 21

Why are beta-blockers used following MI?

Answer 21

• MI causes increased sympathetic activity and beta blockers prevent ventricular arrhythmias
• reduces O2 demand so reduces myocardial ischaemia

Question 22

What do drugs blocking K+ channels do and what effect does this have?

Answer 22

Prolong action potential by blocking K+ channels -> lengthens absolute refractory period

Question 23

Why are drugs which block K+ channels not generally used?

Answer 23

In theory should prevent another AP occurring too soon but in reality can be pro-arrhythmic

Question 24

What is the one exception of drugs blocking K+ channels and what is it used to treat?

Answer 24

Amiodarone - blocks Ca2+ channels, beta blocker and slows down rise of AP

Treats tachycardia associated with Wolff-Parkinson-White syndrome and suppresses ventricular arrhythmias post MI

Question 25

What is Wolff-Parkinson-White syndrome?

Answer 25

Re-entry loop due to extra conduction pathway

Question 26

What are the effects of drugs which block Ca2+ channels?

Answer 26

- decreases slope of AP at SA node - decreases AV nodal conduction - negative inotropy

Question 27

Which Ca2+ channel blockers are ineffective in the heart and where do they work instead?

Answer 27

Dihydropyridine Ca2+ channel blockers don't prevent arrhythmias but act on vascular smooth muscle

Question 28

Which drug doesn't fit into any of the anti-arrhythmic classes but is useful for terminating supra-ventricular tachycardia?

Answer 28

Adenosine

Question 29

What does adenosine act on and what effect does this have?

Answer 29

Acts on alpha-1 receptors at AV node and enhances K+ conductance (hyperpolarises cells of conducting tissue and prevents re-entry loops)

Question 30

What are the features of heart failure?

Answer 30

- reduced force of contraction or reduced filling - reduce cardiac output - reduced tissue perfusion - oedema

Question 31

What are the two types of drugs used in the treatment of heart failure?

Answer 31

- positive inotropes to increase cardiac output | - drugs which reduce work load of heart (reduce afterload and preload)

Question 32

Why are positive inotropes not usually used to treat heart failure?

Answer 32

Don't improve long-term survival

Question 33

Which drugs increase cardiac contractility?

Answer 33

Cardiac glycosides | Beta-adrenergic agonists

Question 34

What is the prototype of cardiac glycosides and what does it block?

Answer 34

Digoxin blocks Na+/K+ ATPase

Question 35

How do cardiac glycosides work?

Answer 35

- Ca2+ extruded via NCX - cardiac glycosides block Na+/K+ ATPase pump - leads to rise in intracellular Na+ - leads to decrease in activity of NCX - causes increase in intracellular calcium as more Ca2+ is stored in SR - increased force of contraction

Question 36

How do cardiac glycosides affect heart rate?

Answer 36

Increase vagal activity -> slows AV conduction -> slows heart rate

Question 37

When can beta-adrenoceptor agonists be used?

Answer 37

To treat cardiogenic shock and acute but reversible heart failure

Question 38

Which drugs reduce workload of the heart?

Answer 38

- ACE inhibitors - beta blockers - diuretics

Question 39

How can ACE inhibitors be used to treat heart failure?

Answer 39

- decreases vasomotor tone -> decreases blood pressure -> reduces afterload of heart - decreases fluid retention -> decreases blood volume -> reduces preload of heart

Question 40

What is angina?

Answer 40

Due to narrowing of coronary arteries, occurs when O2 supply to heart doesn't meet its need (limited duration so no myocyte death) -> chest pain with exertion

Question 41

How is angina treated?

Answer 41

- reduce workload of heart | - improve blood supply to heart

Question 42

Which drugs reduce work load of the heart to treat angina?

Answer 42

Beta-adrenoceptor blockers Ca2+ channel antagonists Organic nitrates

Question 43

Which drugs improve blood supply to the heart?

Answer 43

Organic nitrates | Ca2+ channel antagonists

Question 44

How do organic nitrates work?

Answer 44

Organic nitrates react with thiols (-SH groups) in vascular smooth muscle, causing NO2- to be released and this is reduced to NO (vasodilator)

Question 45

How does nitric oxide cause vasodilation?

Answer 45

- NO activates guanylate cyclase - increases cGMP - lowers intracellular Ca2+ - causes relaxation of vascular smooth muscle

Question 46

What is the primary action of organic nitrates in terms of alleviating symptoms of angina?

Answer 46

Acts on venous system (venodilation lowers preload) - reduces workload, heart fills less, force of contraction reduced, lowers O2 demand

Question 47

What is the secondary action of organic nitrates in terms of alleviating symptoms of angina?

Answer 47

Acts on coronary collateral arteries to improve O2 delivery to ischaemic myocardium

Question 48

Why do organic nitrates preferentially act on veins?

Answer 48

Less endogenous nitric oxide in veins

Question 49

Which heart conditions carry an increased risk of thrombus formation?

Answer 49

Atrial fibrillation Acute MI Mechanical prosthetic heart valves

Question 50

What are two important anticoagulants and how do they work?

Answer 50

1) heparin (IV) - inhibits thrombin | 2) warfarin (orally) - antagonises action of vit K

Question 51

What is an example of an antiplatelet drug and when is it used?

Answer 51

Aspirin - following acute MI or high risk of MI

Question 52

What is hypertension associated with?

Answer 52

Increased blood volume (Na+ and water retention by kidneys) | Increased TPR

Question 53

Which drugs are used to treat hypertension and what are their effects?

Answer 53

1) ACE inhibitors (decrease Na+ and water retention by kidney, decrease TPR) 2) Ca2+ channel blockers selective for vascular smooth muscle (vasodilation) 3) diuretics (decrease Na+ and water retention by kidney) 4) beta blockers (not routinely used, decrease CO) 5) alpha1-adrenoceptor antagonist (not routinely used, vasodilation)