Arrhythmias and Anti-arrhythmic drugs

Question 1

There are two main electrical dysfunction mechanisms. You can have defects in impulse ______ or impulse ______.

Answer 1

There are two main electrical dysfunction mechanisms. You can have defects in impulse formation or impulse conduction.

Question 2

what are the two defects in Impulse formation?

Answer 2

1. SA node automaticity is interrupted or altered (missed beats, ectopic beats)
2. triggered activity

Question 3

There are physiological ways that the SA node activity is modulated e.g. by the ANS (e.g. sinus tachycardia, sinus arrhythmia (this is quite common in _____ people)
However it is also pathological - for example ____ _______.

Answer 3

There are physiological ways that the SA node activity is modulated e.g. by the ANS (e.g. sinus tachycardia, sinus arrhythmia (this is quite common in young people)
However it is also pathological - for example latent pacemakers.

Question 4

what are latent pacemakers?

Answer 4

these are pacemakers outwith the SA node which are just waiting to take over the pacemaking activity i.e overdrive suppression is lost.

Question 5

which two circumstances allow latent pacemakers to activate?

Answer 5

1. when the SA node AP firing frequency is pathologically low or when there is a problem with the conduction of the SA node
2. might also occur if a latent pacemaker firs at a rate which is faster than the SA node firing rate.

Question 6

with a low SA node firing frequency you get an ______ escape beat - latent pacemaker initiates the impulse e.g. the AP is not generated by SA node activity, it has escaped the normal overdrive.

Answer 6

escape beat - latent pacemaker initiates the impulse e.g. the AP is not generated by SA node activity, it has escaped the normal overdrive.

Question 7

when might SA node firing frequency be low?

Answer 7

during intense vagal stimulation

Question 8

with a fast latent pacemaker firing frequency you get an ____ beat

Answer 8

ectopic

Question 9

give some causes of an ectopic rhythm

Answer 9

ischaemia, hypokalaemia, increased sympathetic activity, fibre stretch

Question 10

what are the two kinds of triggered activity?

Answer 10

EAD, DAD

Question 11

which part of the heart often causes EAD?

Answer 11

the purkinje fibres

Question 12

during which two phases do EADs incite the AP?

Answer 12

phase 2 (terminal plateau) and phase 3 (repolarisation)

Question 13

In phase 2 what is the EAD mediated by ?

Answer 13

Ca channels - the repolarisation happens quicker than it would normally

Question 14

In phase 3 what is the EAD mediated by ?

Answer 14

Na channels - they recover from inactivation

Question 15

what is EAD associated with?

Answer 15

prolongation of AP and drugs (e.g. sotalol) prolonging the QT interval (the interval between depolarisation and repolarisation).

Question 16

what dangerous rhythm can EAD lead to?

Answer 16

ventricular fibrillation

Question 17

when do DADs occur?

Answer 17

after complete repolarisation

Question 18

what are DADs associated with?

Answer 18

Ca overload

Question 19

what provokes the Ca overload in DAD?

Answer 19

catecholamines, digoxin, heart failure

Question 20

what are the three mechanisms for defects in impulse conduction?

Answer 20

re-entry, conduction block, accessory tracts

Question 21

what is re-entry?

Answer 21

a self sustaining electrical circuit (anatomically may be due to parallel conduction pathways) which stimulates an area of myocardium repeatedly/ rapidly

Question 22

re-entry
1. normal conduction:
We have a conduction pathway in the heart (possibly the purkinje fibres) which divides into two branches. There is a ______ area between the two branches. APs will travel down both branch 1 and 2 and from these branches they will enter into a mass of _____. The APs try to negotiate their way around the ____ area and this is not normally a problem. The two APs from branch 1 and 2 then meet in the ____ and ______ each other

Answer 22

We have a conduction pathway in the heart (possibly the purkinje fibres) which divides into two branches. There is a non-excitable area between the two branches. APs will travel down both branch 1 and 2 and from these branches they will enter into a mass of ventricle. The APs try to negotiate their way around the non-excitable area and this is not normally a problem. The two APs from branch 1 and 2 then meet in the middle and extinguish each other

Question 23

Re-entry
2. abnormal conduction:
There is _______ conduction block meaning that the AP in branch 1 is ____ but the AP in branch 2 _____ ____ forward - (anterograde conduct).

Answer 23

There is unidirectional conduction block meaning that the AP in branch 1 is fine but the AP in branch 2 cannot conduct forward - (anterograde conduct).

Question 24

re-entry conditions are satisfied if

• the AP is not allowed to progress down its normal direction of branch i.e. unidirectional block - anterograde conduction ______
• the AP can go in the wrong direction but _____ slowly. The AP goes down branch 1, it then goes round the island of non-conducting tissue however, there is no _______ of AP. The AP will continue in a right hand direction but will also go up branch 2 very slowly in a ______ conduction.

Answer 24

• the AP is not allowed to progress down its normal direction of branch i.e. unidirectional block - anterograde conduction prohibited
• the AP can go in the wrong direction but abnormally slowly. The AP goes down branch 1, it then goes round the island of non-conducting tissue however, there is no extinguishing of AP. The AP will continue in a right hand direction but will also go up branch 2 very slowly in a retrograde conduction.

Question 25

why is the slow retrograde in re-entry important?

Answer 25

if means that branch 1 is no longer refractory - ie has recovered from inactivation so the AP meets excitable tissue once more without an impulse having to come from the point before branching

Question 26

what is the movement of APs in a circle called?

Answer 26

circus movement

Question 27

what is first degree AV block?

Answer 27

the tissue conducts all impulses but more slowly than usual

Question 28

what happens in intermittent block?

Answer 28

the tissue conducts some impulses but not others - example second degree AV block

Question 29

accessory tracts - some individuals possess electrical pathways that bypass the _____. Conduction through accessory pathways is relatively ____-

Answer 29

some individuals possess electrical pathways that bypass the AV node conduction through accessory pathways is relatively rapid

Question 30

name a common accessory tract pathway

Answer 30

bundle of kent

Question 31

in accessory tracts the ventricles receive impulses from both the ____ and _____ pathways - can set up the condition for a ______ loop predisposing to tachyarrhythmias

Answer 31

ventricles receive impulses from both the normal and accessory pathways - can set up the condition for a re-entrant loop predisposing to tachyarrhythmias

Question 32

name an antiarrhythmic drug which is not entirely selective blocker of Na, K or Ca channels

Answer 32

amiodarone

Question 33

name two drugs which do not fit into the vaughn williams classification

Answer 33

adenosine and digoxin

Question 34

what is the channel target for class 1 drugs ?

Answer 34

VA Na channels

Question 35

Class 1a: | associate and dissociate from Na channels at a______ rate. They ___ rate of rise of AP and_____ the refractory period

Answer 35

Class 1a: associate and dissociate from Na channels at a moderate rate. They slow rate of rise of AP and prolong the refractory period

Question 36

Class 1b: | associate and dissociate from Na channels at a ____ rate. Prevent premature beats

Answer 36

Class 1b: | associate and dissociate from Na channels at a rapid rate. Prevent premature beats

Question 37

Class 1b: | associate and dissociate from Na channels at a ____ rate. Depress c______

Answer 37

Class 1b: | associate and dissociate from Na channels at a slow rate. Depress conduction

Question 38

name a class 1a drug

Answer 38

disopyramide

Question 39

name a class 1b drug

Answer 39

lignocaine

Question 40

name a class 1c drug

Answer 40

flecainide

Question 41

what is the channel target for class II drugs ?

Answer 41

beta adrenoceptors (as antagonists)

Question 42

what is the action of Class II

Answer 42

decrease the rate of depolarisation in SA and AV node

Question 43

name a class II drug

Answer 43

metoprolol

Question 44

what is the channel target for class III drugs ?

Answer 44

VA K channels (plus others)

Question 45

what is the action of Class III

Answer 45

prolong the AP duration - increasing refractory period

Question 46

name a class III drug

Answer 46

amiodarone

Question 47

what is the channel target for class IV drugs ?

Answer 47

VA Ca channels

Question 48

what is the action of Class IV

Answer 48

slow conduction in SA and AV nodes. Decrease the force of cardiac conduction

Question 49

name a class IV drug

Answer 49

verapamil

Question 50

which class of drugs are used in WPW?

Answer 50

classs 1

Question 51

what are the three conformational states that Na channels exist in? the relative time spent in each depend upon firing frequency

Answer 51

1. resting - nonconducting state 2. open (conducting state) 3. inactivated (refractory period)

Question 52

Na channel: During high frequency firing (e.g. tachyarrhythmias) relatively more time is spent in the ____ and _____ states.

Answer 52

During high frequency firing (e.g. tachyarrhythmias) relatively more time is spent in the open and inactivated states.

Question 53

Class 1 agents bind preferentially to these targeting areas of the myocardium in which firing frequency is ____ in a use-dependent manner without preventing the heart from beating at normal frequencies.

Answer 53

Class 1 agents bind preferentially to these targeting areas of the myocardium in which firing frequency is highest in a use-dependent manner without preventing the heart from beating at normal frequencies.

Question 54

what do class I agents do to the conducting state?

Answer 54

they block it

Question 55

what do class I agents do to the inactivated state?

Answer 55

they stabilise it

Question 56

Class 1 agents dissociate from the Na channel when it is in the ____ state (i.e. during ____)

Answer 56

Class 1 agents dissociate from the Na channel when it is in the resting state (i.e. during diastole)

Question 57

``` class I drugs: Thus, if heart rate increases, less time is available for ______ and more time available for ______. Steady state block increases, particularly for agents with slow dissociation rates. LIKE CLASS 1C. ```

Answer 57

Thus, if heart rate increases, less time is available for unblocking (dissociation) and more time available for blocking (association). Steady state block increases, particularly for agents with slow dissociation rates. LIKE CLASS 1C.

Question 58

``` class I drugs In _____ myocardium, myocytes are partially depolarised and the action potential is of l_____ duration thus: - The inactivated state of the Na channel is available to Na channel blockers for a ____ period of time - The rate of channel recovery from block is ______ ```

Answer 58

In ischaemic myocardium, myocytes are partially depolarised and the action potential is of longer duration thus: The inactivated state of the Na channel is available to Na channel blockers for a greater period of time The rate of channel recovery from block is decreased

Question 59

``` class I drugs Collectively the higher affinity of Na channel blockers for the ___ and ___ states of the channel allows them to act _____ on ischaemic tissue and block an arrhythmogenic focus at its source. This is because ischaemic myocaytes are partially ____ - and so ‘The inactivated state of the Na channel is available to Na channel blockers for a greater period of time’ as above. ```

Answer 59

Collectively the higher affinity of Na channel blockers for the open and inactivated states of the channel allows them to act preferentially on ischaemic tissue and block an arrhythmogenic focus at its source. This is because ischaemic myocytes are partially depolarised - and so ‘The inactivated state of the Na channel is available to Na channel blockers for a greater period of time’ as above.

Question 60

which classes of drugs are used for atria (rate control of SVT) ?

Answer 60

classes Ic and III

Question 61

which classes of drugs are used for ventricles ?

Answer 61

classes 1a Ib, II

Question 62

which classes of drugs are used for AV node (rhythm control of SVT) ?

Answer 62

adenosine, dogoxin, classes II, IV

Question 63

which classes of drugs are used for atria and ventricles, AV accessory pathways?

Answer 63

amiodarone, sotalol, classes Ia Ic

Question 64

what does adenosine do?

Answer 64

activates A1 adenosine receptors coupled to Gi which opens ACh senistive K channels (GIRK) just like ACh would

Question 65

adenosine ______ the AV node briefly so the slope of the pacemaker potential ______, suppressing impulse conduction

Answer 65

hyperpolarizes the AV node briefly so the slope of the pacemaker potential decreases , suppressing impulse conduction

Question 66

what is adenosine used to treat?

Answer 66

PSVT termination

Question 67

what causes PSVT?

Answer 67

re-entry involving the AV node SA node or atrial tissue

Question 68

with adenosine threshold does not changes - just the _______.

Answer 68

Threshold does not changes - just the time taken to reach it.

Question 69

what are some side effects of adenosine?

Answer 69

anxiety and sense of impending doom

Question 70

what does verapamil do?

Answer 70

blocks L-type Ca channels

Question 71

verapamil ____ conduction and _____ refractory period in ___ node and ________

Answer 71

slows conduction and prolongs refractory period in AV node and bundle of His

Question 72

what is verapamil used to treat?

Answer 72

atrial tachycardia, SVT, atrial fib and flutter, AVRT (wPW)

Question 73

at high doses what may verapamil cause?

Answer 73

heart block

Question 74

verapamil should be used with great caution in combination with other drugs that have a ____ inotropic effect - because these already suppress calcium in the cell.

Answer 74

It should be used with great caution in combination with other drugs that have a negative inotropic effect - because these already suppress calcium in the cell.

Question 75

what does lignocaine do?

Answer 75

rapidly blocks Na channels - blocks inactivated with little effect on open channels

Question 76

Due to rapid unblocking, lidocaine primarily affects Na channels in areas of the myocardium that discharge action potentials at a ____rate (e.g. ischaemic zone)

Answer 76

Due to rapid unblocking, this drug primarily affects Na channels in areas of the myocardium that discharge action potentials at a high rate (e.g. ischaemic zone)

Question 77

what is lidocaine used in?

Answer 77

ventricular arrhythmias - tachycardias

Question 78

disopyramide is used (orally) to prevent recurrent _____ _____, procainamide (IV) is used to treat ventricular arrhythmias following ___

Answer 78

disopyramide is used (orally) to prevent recurrent ventricular arrhythmias, procainamide (IV) is used to treat ventricular arrhythmias following MI

Question 79

what is fleccainide used for?

Answer 79

paroxysmal AF - it has a negative inotropic action and may trigger serious ventricular arrhythmias

Question 80

what are propranolol and atenolol used in treatment for?

Answer 80

supraventricular tachycardias- basically all of them, AF, AVNRT, AVRT premature ventricular complex

Question 81

how do amiodarone and sotolol work?

Answer 81

they slow repolarization of the AP by block of voltage activated K channels and hence increase in AP duration and the effective refractory period SUPPRESSES RE-ENTRY

Question 82

what is amiodarone used for treatment in?

Answer 82

stable VT, AF, AVNRT

Question 83

Amiodarone is effective when many other drugs have failed and reduces mortality after ____ and in ____

Answer 83

Amiodarone is effective when many other drugs have failed and reduces mortality after MI and in congestive heart failure

Question 84

what are some examples of the adverse effects of amiodarone

Answer 84

- pulmonary fibrosis - thyroid disorders - photosensitivity reactions - peripheral neuropathy