heart

Question 1

3 aims of treating cardiac rhythm disturbances (arrhythmias/dysrhythmias)

Answer 1

reduce sudden death, prevent stroke, alleviate symptoms

Question 2

5 things management of cardiac rhythm disturbances may involve

Answer 2

drug therapy, cardioversion, pacemakers, catheter ablation therapy, implantable defibrillators

Question 3

effect on heart rate of cardiac rhythm disturbances

Answer 3

may increase (tachyarrhythmias) or decrease (bradyarrhythmias)

Question 4

3 simple classifications of arrhythmias based on site of origin

Answer 4

supraventricular (usually atria), ventricular, complex (supraventricular and ventricular)

Question 5

2 drugs used to treat supraventricular arrhythmias

Answer 5

amiodarone, verapamil

Question 6

2 drugs used to treat ventricular arrhythmias

Answer 6

flecainide, lidocaine

Question 7

drug used to treat complex arrhythmias

Answer 7

disopyramide

Question 8

other method of classification of arrhythmias, which is of limited clinical significance

Answer 8

Vaughan Williams

Question 9

what is Vaughan Williams classification, what are the 4 methods it distinguished between and why is it clinically limited

Answer 9

method of classsifying anti-arrhythmic drugs (either blocks Na+ channels, preventing depolarisation; blocks B-receptors, inhibiting muscular contraction; blocks K+ channels, preventing repolarisation; or Ca2+ channel blockers; drugs have mixed mechanisms so fall into many classes so not clinically useful

Question 10

4 examples of anti-arrhythmic drug

Answer 10

adenosine, verapamil, amiodarone, digoxin (cardiac glycosides)

Question 11

how is adenosine uses as an anti-arrhythmic drug (administration, classification of arrhythmia, length of actions vs verapamil)

Answer 11

IV to terminate supraventricular tachyarrhthymias; short-lived actions (20-30s), so safer than verapamil

Question 12

adenosine pathway in coronary vascular smooth muscle causing relaxation

Answer 12

adenosine binds to adenosine type 2A (A 2A) receptors, which are coupled to Gs-protein -> Gs-protein activation -> upregulates cAMP by adenylyl cyclase -> PKA activation/myosin light chain kinase inactivation -> stimulation of K ATP channels/decreased myosin phosphorylation -> hyperpolarisation of smooth muscle/decrease in contractile force -> relaxation; adenosine also inhibits Ca2+ entry into cell through L-type Ca2+ channels

Question 13

adenosine pathway in cardiac tissue causing cell hyperpolarisation and inhibition of Ca2+ entry

Answer 13

adenosine binds to adenosine type 1 (A 1) receptors, which are coupled to Gi-protein -> Gi-protein activation -> opening of K+ channels/decrease cAMP -> cell hyperpolarisation/inhibition of L-type Ca2+ channels and Ca2+ entry

Question 14

adenosine pathway in SAN pacemaker cells causing negative chronotropy

Answer 14

adenosine binds to adenosine type 1 (A 1) receptors, which are coupled to Gi-protein -> Gi-protein activation -> decreases cAMP -> inhibits pacemaker current I f -> decreases slope of phase 4 of pacemaker action potential (repolarisation) -> decreases spontaneous firing rate (negative chronotropy) -> more regular heart rate as increased time do increased likelihood of regular depolarisations

Question 15

use of verapamil as anti-arrhythmic drug

Answer 15

reduction of ventricular responsiveness to atrial arrhythmias

Question 16

verapamil mechanism of action as anti-arrhythmic drug

Answer 16

block Ca2+ channels, so depresses SAN automatically and subsequent AVN conduction, so more regular heart rate as increased time do increased likelihood of regular depolarisations

Question 17

goal of amiadarone and other anti-arrhythmic drugs

Answer 17

alter effective refractory period or conduction velocity, thereby hopefully abolishing reentry mechanisms

Question 18

what happens in the effective refractory period

Answer 18

tissue is not excitable

Question 19

propogation of signal across normal cardiac muscle (triangle of branch 1, 2 and 3), and in heart failure if branch 2 is dead

Answer 19

action potential passes down branch 1 and 2 -> moves onto other parts of cardiac muscle -> if came across each other at branch 3, cancel each other out; if dead tissue in heart failure it is unidirectional, so e.g. can’t pass down branch 2, so at branch 3 no cancelling out and works way up branch 2 to reactivate tissue, causing jerky contractions

Question 20

how does the state of cardiac tissue when the action potential arrives determine whether an arrhythmia occurs

Answer 20

depends whether tissue can be depolarised or not (whether in effective refractory period), so sometimes jerky contractions, othertimes not

Question 21

how does amiodarone prevent arrhythmias of re-entry

Answer 21

amiodarone has multiple ion block, including blocking K+ channels, so left in repolarisation state longer (effective refractory period), so won’t be able to depolarise as much, so chance of re-entry rhythm causing extra contractions decreases

Question 22

adverse effects of amiodarone

Answer 22

accumulates in body, causing photosensitive skin rashes, hypo/hyper thyroidism and pulmonary fibrosis

Question 23

2 conditions digoxin is used to treat as an anti-arrhythmic drug

Answer 23

atrial fibrillation and atrial flutter

Question 24

how does digoxin exert a positive inotropic effect as an anti-arrhythmic drug

Answer 24

inhibits Na+/K+-ATPase pump -> Na+ can’t move out cell, so can’t be available for Na+/Ca2+ exchange -> Ca2+ remains inside cell -> increased IC Ca2+ -> positive inotropic effect

Question 25

what is the effect of central vagal stimulation by digoxin

Answer 25

increased refractory period, reduced rate of conduction through AVN (PSNS-like effects)

Question 26

how is digoxin used as an anti-arrhythmic drug when treating atrial fibrillation and flutter which lead to rapid ventricular rate, impairing ventricular filling (due to decreased filling time) and reducing cardiac output

Answer 26

via vagal stimulation, digoxin reduces conduction of electrical impulses within AVN, so fewer impulses reach ventricles, reducing ventricular rate so more rhythmical contractions, with more powerful contractions (positive iontropic effect, increasing cardiac output)

Question 27

adverse effect of digoxin as an anti-arrhythmic drug

Answer 27

dysrhythmias (e.g. AV conduction block, ectopic pacemaker activity)

Question 28

why does hypokalaemia (e.g. by diuretic use) lower threshold for digoxin toxicity

Answer 28

as digoxin targets Na+/K+-ATPase pump, K+ is competing for binding side, so if hypokalaemic, digoxin binds more easily as not as much competition