12. Arrhythmias And Drugs

Question 1

What are the 2 types of after depolarisations (triggered activity)? When is each more likely to happen?

Answer 1

Delayed after-depolarisations (return to resting membrane potential, then another spike) - intracellular Ca2+ high.
Early-after depolarisations (oscillations) - action potential prolonged, so longer QT.

Question 2

What happens in normal spread of excitation at a branch point?

Answer 2

Excitation reaches branch point, spreads both ways, cancels out where meets.

Question 3

What happens when excitation meets a branch point and there is a block of conduction through a damaged area?

Answer 3

Does not spread down damaged branch, doesn’t really cause any problems.

Question 4

What happens when excitation reaches a branch with a unidirectional block (incomplete conduction damage)?

Answer 4

Excitation takes a long route to spread the wrong way through the damaged area, so as excitation never meets to cancel out, sets up a circus of excitation.

Question 5

What arrhythmia is caused by multiple re-entrant circuits in the atria?

Answer 5

Atrial fibrillation

Question 6

What happens in AV nodal re-entry?

Answer 6

Fast and slow pathways in the AV node create a re-entry loop leading to palpitations.

Question 7

What happens in ventricular pre-excitation? Give an example of a syndrome this occurs in

Answer 7

Accessory pathway between atria and ventricles creates a re-entry loop eg Wolff-Parkinson White syndrome.

Question 8

How do the anti-arrhythmic drugs, voltage-dependant Na+ channel blockers work?

Answer 8

Are a use-dependent block. Block voltage-gated Na+ channels in open or inactive state, so preferentially block damaged depolarised tissue.

Question 9

What do drugs that block voltage-dependant Na+ channels have little effect in normal cardiac tissue?

Answer 9

Dissociates rapidly - blocks during depolarisation but dissociated in time for next AP, so has no effect on AP generation.

Question 10

Why are drugs which block voltage-dependant Na+ channels sometimes given following an MI?

Answer 10

Given IV - if patient shows signs of ventricular tachycardia, as damaged areas of myocardium may be depolarised and fire automatically. There are more Na+ channels open in depolarised tissue, and so blocks those Na+ channels and prevent automatic firing.

Question 11

How do the anti-arrhythmic drugs, beta-adrenoreceptor antagonists, work?

Answer 11

Block sympathetic action by acting on beta1-adrenoreceptors in the heart. Slow down pacemaker potential, and slow conduction at AV node.

Question 12

When are beta-blockers used and why?

Answer 12

Prevent supraventricular tachycardia and slows ventricular rate in patients with AF - slows conduction in AV node.
Following MI - Mi causes increased sympathetic activity, arrhythmias partly due to increased sympathetic activity, so beta-blockers prevent ventricular arrhythmias. Also reduces O2 demand, reducing myocardial ischaemia.

Question 13

How do the anti-arrhythmic drugs, K+ channel blockers, work?

Answer 13

Prolong the action potential by blocking K+ channels, lengthening the absolute refractory period. Prevents another action potential occurring too soon.

Question 14

Why are K+ channel blockers not generally used?

Answer 14

In theory prevent another action potential occurring too soon, but can actually by pro-arrhythmic.

Question 15

What type of anti-arrhythmic drug is amiodarone and what is it used clinically when other drugs of this type aren’t and why?

Answer 15

Blocks K+ channels, but also has other actions.
Used to treat tachycardia associated with Wolff-Parkinson-White syndrome.
Affective for suppressing ventricular arrhythmias post MI.

Question 16

How do the anti-arrhythmic drugs, Ca2+ channel blockers, work?

Answer 16

Decrease slope of action potential at SA node and decreases AV nodal conduction, as well as force of contraction.

Question 17

Where do dihydropyridine Ca2+ channel blockers work and not work?

Answer 17

Not effective in preventing arrhythmias but do act on vascular smooth muscle.

Question 18

What antiarrhythmic drug can be administered IV, but is also already produced endogenously in the body? What does it do?

Answer 18

Adenosine - enhances K+ conductance, so hyperpolarises cells of conducting tissue. Is anti-arrhythmic and useful for terminating re-entrant supraventricular tachycardia (as cells take longer to be able to be depolarised again).

Question 19

What do positive inotropes, eg cardiac glycosides and beta-adrenergic agonists, do and why are they not routinely used to treat heart failure?

Answer 19

Increase cardiac output. Improve symptoms but not long term survival.

Question 20

What is the action of cardiac glycosides?

Answer 20

1. ) Blocks Na+/K+ ATPase, yet Na+/Ca2+ exchanger still functioning, so leads to rise in Na+ concentration inside cells. Rise in Na+ concentration means left Na+ is moved in by Na+/Ca2+ exchanger, and so less Ca2+ moved out of cell, increasing force of contraction.
2. ) Increase Vargas activity, slowing Av conduction and HR.

Question 21

When are you most likely to use the positive inotrope cardiac glycosides?

Answer 21

In heart failure when there is an arrhythmia such as AF.

Question 22

What do the positive inotropes, beta-adrenoreceptor agonists, act on and what does this cause?

Answer 22

Beta1-receptors, increase myocardial contractility.

Question 23

When are the positive inotrope, beta-adrenoreceptor agonists, used?

Answer 23

Cardiogenic shock, and acute but reversible heart failure.

Question 24

How do ACE-inhibitors work to reduce the workload of the heart in treatment of heart failure?

Answer 24

Decrease vasomotor tone, reduce afterload of heart. Decrease fluid retention, reduce preload of heart, reduce workload of heart.

Question 25

Name 2 drugs other than ACE-inhibitors that reduce the work load of the heart, and can therefore be used in the treatment of heart failure.

Answer 25

Beta-blockers.

Diuretics.

Question 26

What are the two main modes of action from treating angina? Give an example of a drug that does each

Answer 26

Reduce the workload of the heart eg beta-adrenoreceptor blockers, Ca2+ channel antagonists, organic nitrates.
Improve blood supply to the heart eg organic nitrates, Ca2+ channel antagonists.

Question 27

What is the action of organic nitrates? How does this help alleviate angina?

Answer 27

React with thiols in vascular smooth muscle, NO2- is released, which is reduced to NO which is a powerful venodilator. No activated granulate cyclase, increases cGMP, lowers intracellular Ca2+ conc, leading to relaxation of vascular smooth muscle.
Thus reduces preload of heart, reducing force of contraction and therefore O2 demand of the heart. Small dilatory affect on collateral arteries of heart (but not many collaterals as mostly end arteries), improving O2 delivery to ischaemic myocardium.

Question 28

Give an example of a drug that is an organic nitrate

Answer 28

GTN spray

Question 29

Why do organic nitrates preferentially act on veins?

Answer 29

Less endogenous nitric oxide in veins.

Question 30

Name 3 heart conditions that carry an increased risk of thrombus formation

Answer 30

AF.
Acute MI.
Mechanical prosthetic heart valves.

Question 31

How does the anticoagulant Heparin work? Therefore when is it used?

Answer 31

Inhibits thrombin, so used acutely for short term anti thrombotic actions.

Question 32

How does the anticoagulant Warfarin work? Therefore when is it used?

Answer 32

Antagonises action of vitamin K. Used long-term.

Question 33

What is the benefit of using the anticoagulant, direct acting oral thrombin inhibitors?

Answer 33

Don’t need usual blood tests as you would with warfarin.

Question 34

When would you use the antiplatelet drug aspirin?

Answer 34

Following acute MI or high risk of MI.