anti-arrhythmic drugs Flashcards
electrophysiology of the heart
what generates AP and where does the signal go from here?
SAN generates the pacemaker potentials hence the driver of electrical activity throughout heart
conducted to atrium
Av node (slow down conduction between atrium + ventricles) for good fill in the ventricles to allow appropriate ejection
bundle branches
purkinje fibres
ventricles
cardiac cycle related back to action potential graphs
when is diastole?
when is systole?
what is plateau phase?
plateau phase = contraction + relaxtion phase hence q-t part of ecg
systole = falling of peak hence after ap which leads to contraction
diastole = rising of peak hence building up to ap
Arrythymia - definition
Abnormalities in heart rhythm
hence heart can’t fill with blood or eject properly so won’t produce correct SV or CO
Arrythymia - symptoms
Palpitations, dizziness, fainting, fatigue, loss of conscious, cardiac arrest, blood coagulation (e.g. stroke, MI)
Arrythymia - causes
list some causes
explain issue with heart block? ischemia?
Cardiac ischemia (MI, angina), heart failure, hypertension, coronary vasospasm, heart block, excess sympathetic stimulation
Heart block -> atrials beat independendtly of heart therefore inappropriate ejection of blood from heart
Ischemia -> can change the initiation of Ap or conduction
Arrythymia - origin
2 origins?
Supraventricular (above the ventricles - SA node, atria, AV node)
Or
Ventricular
Arrythymia - effect (2)
Tachycardia (>100 bpm) or Bradycardia (<60 bpm)
Common arrhythmias (5)
atrial fibrillation (AF), supraventricular tachycardia (SVT), Heart block, Ventricular tachycardia (VT) or Ventricular fibrillation (VF)
atrial fibrillation (AF)
what is this? how to identify?
effect of this on ventricles?
clincial issue in atria?
atrial quivers because it generates its own electrica; activity (too fast activity) therefore there is no distinct P wave
in appropiate conduction to ventricles hence ventricles won’t conduct properly which leads to poor CO but also atrial don’t eject blood properly therefore holds onto blood
Stasis can cause clots (as it holds onto blood) and can cause strokes
supraventricular tachycardia (SVT
how to identify?
what is this? why doies this occur?
P wave buried in T wave
Fast ventricular contractions
Lots of QRS waves therefore high ventricle activity which is happening above ventricles so inappropiate conduction causing too fast V activity and this makes it hard to see the P wave (atrial contraction)
Heart block
what is this? what doies it affect? how does it relate to ecg?
Failure of the conduction system
(e.g. SA, AV, or bundle of his)
Uncoordinated atria/ventricular contractions
This means that the P wave may not relate to the qrs wave
Ventricular tachycardia (VT) and Ventricular fibrillation (VF)
what is this and the difference between the two?
what effect do these two have on the heart? effect on body?
VT = fast and REGULAR
VF = fast and IRREGULAR
Both are serious as can’t fill heart properly and can’t eject enough blood therefore heart not generating SV + CO as it should be which leads to poor perfusion to end organs like heart + brain
Mechanisms of Arrhythmogenesis - abnormal impulse generation
what two reasons could this automatic rhthymns be due to? 2 causes of triggered rhthymns?
due to
Automatic rhythms - increased SA node activity, ectopic activity (ectopic means atrial or ventricles generate own activity)
Triggered rhythms – Early-after depolarisations (EADs), delayed-after depolarisations (DADs)
Mechanisms of Arrhythmogenesis - Abnormal Conduction
what is it and what does it cause?
Re-entry electrical circuits in heart
Conduction block
abnormal impulse generation - ectopic pacemaker activity
where is pacemaker activity generated? what is ectopic pacemaker activity?
give examples (4)
what are these enhanced by? (3)
how does this link to risk factor for arrythmia?
what drug to use?
Pacemaker activity is initiated in SA node but other areas of the heart can have pacemaker activity to ‘safeguard’ against SA node damage
SA node = 60-70/s
AV node = 40-60 /s
Bundle of His = 30-40/s
Purkinje fibres = 15-25/s
These other ‘pacemaker’ areas are greatly enhanced
by sympathetic nerve activity by:
Increase heart rate
Increasing AV node conduction
Increase excitability of ventricular tissue
Hence continuous/enhanced stimulation of sympathetic nervous system (stress, heart failure) can lead to arrhythmias
Hence use of Class II anti-arrhythmic drugs such as B-blockers
abnormal impulse generation - EADS
what causes this? example of how it can take place?
Early-after-depolarisation (EAD)
Altered ion channel activity
e.g. Abnormal increase in Na or Ca channel activity
therefore can trigger another ap on top of the original ap
abnormal impulse generation - DADS
what is abnormal and how does it set off Ap?
Abnormal levels of Ca2+ in SR
Ca2+ leaks out into cytosol - Ryr receptor leaky
Stimulate Na/Ca exchanger (NCX)
Na+ influx – depolarisation
Abnormal Impulse Conduction : Re-entry
what is the basis for the SAN to ventricles wave conduction pathway? how does the wave work?
what will damage to heart mean?
how are ichemic areas different?
overall effect of this?
Basis for the SAN to ventricles ‘wave’ conduction pathway of the heart is:
Action potentials stop conducting because surrounding tissue is refractory Cannot conduct anymore APs
(depolaristion -> repolarisation -> refraction -> depolarisation)
But : Damage to myocardium means that some areas of the heart are more conductive than others – produces RE-ENTRY pathways
ichemic areas can become conduction blocks
Slows/Stops orthograde impulses
Allows retrograde impulses from 3 to 2
to be conducted when
refractory period is over in 1 and 2
Causes premature impulses to go from 2 to 1
Disturbed action potentials through 1
which means stimulation, depolarisation, further depolarisation and then refractory allows it to pass
Abnormal Impulse Conduction : Heart block
what is it due to?
identifying first degree? second degree? 3rd?
what can this cause?
Due to fibrosis / ischaemic damage of conducting pathway (Often AV node issue)
First degree : P-R interval >0.2 s
Second degree : >1 atria impulses fail to stimulate ventricles
Third degree (complete block) : atria and ventricles beat independently of one another
Ventricles contract at slow rate, depending on what ectopic pacemaker sets the rate
(e.g. Bundle of his, ventricular tissue)
Can cause loss of consciousness
Adams-Stokes attacks – syncope (fainting)
Treatment of Arrhythmias - goal
2 goals
Restore sinus rhythm and normal conduction
Prevent more serious and possibly fatal arrhythmia occurring
Treatment of Arrhythmias - how to achieve this
3 different ways
Reduce conduction velocity
Alter refractory period of cardiac action potentials
Reduce automaticity (decrease EADs, DADs, Ectopic beats)
Anti-Arrhythmic drugs
what are the 4 classes and where do they act and what do they act on?
Class I : Na+ channel blockers (non-nodal tissue) pahose 0
Class II : β blockers (nodal and non-nodal tissue) -> Class II act at SA & AV nodes and Atria/Ventricles
Reduce excitability of cardiac tissue
Class III : K+ channel blockers (non-nodal tissue) - phase 3
Class IV : Ca2+ channel blockers (nodal and non-nodal tissue) - phase 0 and phase 2
Non-classified drugs
Class I : Na+ channel blockers (non-nodal tissue)
where do they act?
what is unique about this blocker and doesn’t stop heart beating?
Block Na+ channels in non-nodal tissue, e.g. atria/ventricles
Block Na+ channels in their in-activated state
Have property of Use-dependence
Only block Na+ channels in high frequency firing tissue
Low activity - Na+ channels return to closed state
High activity - lots of Na+ channels in
in-activated state so drug can act on this
how does the class I drug work?
what happens when it binds in inactivated state?
what does it inhibit?
example of drug?
treated for?
drug binds to the inactivated state
Fast dissociating drug (off channels in <0.5 s)
- drugs comes off in-activate site in time for next impulse therefore no effect on normal firing
Fast dissociating drug
still bound to in-activate site when next impulse arrives inhibits high frequencies as drug can stay for long period of time and prevent AP of next AP
e.g. Lidocaine
For very fast arrhythmia, e.g. VT and VF
Class II drugs – β-blockers
what is arrhythmia usually associated with?
what does this usually lead to the activation of?
what 2 things does this cause?
name a B1 blocker
what 2 things does it do?
what does this achieve?
Increased sympathetic activity associated with arrhythmias
Stimulation of sympathetic nerves leads to activation of β1 receptors in heart causing :
Increase in SA node and AV node firing rate
Increase ventricular excitability by raising [Ca2+]i
Both these effects on the heart are pro-arrhythmic
β1 blockers, e.g. atenolol
Reduce VT after myocardial infarctions
caused by increase in sympathetic nerve activity
Slows initiation of pacemaker potentials in SAN, and slows conduction through AV node to reduce ventricular firing rate in SVT
Class III drugs – K+ channel blockers
what does increasing the length of APs do?
how can we do this?
where are these and which part do we not target?
what is the rationale of this drug?
name an example drug and what these drugs work well with
what condition is this used for?
Increasing the length of the action potential increases refractory period of heart (can not fire another action potential as it will plateau and can’t activate na channels for firing)
Inhibit K+ channels responsible for repolarisation in atria/ventricles
(not K+ channels in SA/AV nodes)
Rationale : block channels that involved in repolarisation – maintain depolarisation – Na+ channels are in-activated – cannot firing any more action potentials – prevent arrhythmias
Class III, e.g. amiodarone, sotalol (also combined Class II actions)
Used for SVT and VT
Class IV drugs – Ca2+ channel antagonists
what do ca2+ channels affect? (2 things)
where else are these channels found? effect of this?
solution\/
example of drugs
used for?
Block of L-type voltage-gated Ca2+ channels mainly affects firing of SA and AV nodes (but also Phase 2 of atria/ventricle)
L-type Ca2+ channels also found on vascular smooth muscle and are involved in vasoconstriction – so blockers can produce relaxation of blood vessels and decrease in blood pressure
Class IV, e.g. Verapamil (more cardiac specific), diltiazem (cardiac and vascular smooth muscle)
Used to control ventricular response rate in SVT
Non-Classified drugs
3 drugs?
what do they do?
where do they act?
what are they used for?
Adenosine
Decreases activity in SA and AV node via hyperpolarisation from opening k+ channels
Used for SVT
Atropine
Muscarinic antagonist
Reduce parasympathetic activity
May be used to treat sinus bradycardia (very low HR) after MI
Digoxin
Central effects, increases vagus nerve activity,
decrease heart rate, and conduction
Used for AF
Paradox: Anti-arrhythmic drugs can be pro-arrhythmic
what can class III drugs increase? what is this called and how does it cause arrhythmia?
what may class I, II and IV increase? and reduce? and how may this lead to arryhtmia?
what else can class IV drugs do?
Caution:
Class III drugs increases QT duration
Long QT syndrome - arrhythmia – due to EADs and DADs generation
Classes I, II, and IV may increase refractory period (less SA, AV, atria/ventricular firing) and reduce conduction time -> Potentially pro-arrhythmic
Class IV may also reduce contractility
sinus tachycardia treatment
goal? which type of drugs to use?
Goal - Slow down SA node
drugs - Class II, III, IV
Atria fribrillation treatment
goal? which type of drugs to use?
goal - Reduce atria activity, return of atria output, prevent clot formation
drugs - II, III, IV, digoxin, anticoagulants
supra ventricular tachycardia treatment
goal? which type of drugs to use?
goal - reduce ventricular response rate
drugs - Class II, III, IV, adenosine
Heart block treatment
goal? which type of drugs to use?
goal - Coordinate atria/ventricular contractions
drugs - Pacemaker required
VT/VF treatment
goal? which type of drugs to use?
goal - Reduce ventricular activity, return ventricular output drugs - class I, II, III
