Lecture 8 - Antiarrhythmics Flashcards
What is the process of generating an action potential in a cardiac myocyte?
AP arrives from neighbouring cells
VG Na+ channels open
Na+ influx (rapid upstroke)
Slight repolarisation as K+ efflux occcurs
Plateau happens as Ca2+ start to be influxed and K+ continues to be effluxed
VG Ca2+ channels close and VG K+ channels open K+ continues to be effluxed so rapid repolarisation occurs
VG K+ channels close
RMP is returned to and maintained by Na/K+ ATPase
Go to slide 4:
Describe what’s happening in Step 0 of the Cardiac myocyte AP:
AP arrives from neighbouring cells
VG Na+ channels open
Na+ influx (rapid upstroke/depolarisation)
Go to slide 4:
Describe what’s happening in Step 1 of the Cardiac myocyte AP:
Slight repolarisation as K+ efflux occcurs
Go to slide 4:
Describe what’s happening in Step 2 of the Cardiac myocyte AP:
Plateau happens as Ca2+ start to be influxed and K+ continues to be effluxed
Go to slide 4:
Describe what’s happening in Step 3 of the Cardiac myocyte AP:
VG Ca2+ channels close and VG K+ channels open K+ continues to be effluxed so rapid repolarisation occurs
Go to slide 4:
Describe what’s happening in Step 4 of the Cardiac myocyte AP:
Voltage gated K+ channels close
RMP is returned to and maintained by Na/K+ ATPase
What principle generates the pacemaker potential at the SAN?
Funny current
Where HCN channels are always open leading to gradual movemtn of Na+ into the SAN cells
What are the stages to generating an action potential in the SAN (Pacemaker potential)?
HCN channels are open so Na+ gradually moves into SAN cells producing the Funny Current
Once threshold met, rapid depolarisation/upstrokek occured due to Ca2+ influx through L-Type voltage gated calcium channels
At peak, Voltagee gated Ca2+ channels close and Voltage gated K+ channels open allowing K+ efflux so REPOLARISATION occurs
What is the 4 main classes of Anti-arrhythmetic drugs in the Vaughan Williams classification?
Class I (Voltage gated Na+ channel Blockers)
Class II (Beta blockers)
Class III (Voltage gated K+ channel Blockers)
Class IV (Calcium Channel Blocker)
What are the 3 classes of Class I anti-arrhythmetic drugs?
Class 1A
Class 1B
Class 1C
What is the best example of a Class 1B anti-arrhytmetic?
What channels does it block?
Lidocaine
Voltage gated Sodium channels
What is the best example of a Class 1C anti-arrhythmetic drug?
What channel does it block?
Flecainide
Voltage gated sodium channels
What is the general principle for how Class I anti-arrhythmetic drugs work?
Block the VG sodium channels slowing the intital upstroke/making it take longer for the upstroke/rapid depolarisation to occur in the cardiac myocytes
How do Class IB anti-arrythmetics work?
What is an example of a Class IB anti-arrhythmetic?
Target cardiac myocytes ONLY IN VENTRICLES
Causes a blockade of VG Na+ channels preventing additional impulses occurring
Lidocaine
What type of tissue do Class IB preferentially target?
Give an example of a Class IB anti-arrhthymetic:
So what condition is it good for?
Damaged heart tissue
Lidocaine
Myocardial Infarction
What is the relative speed by which Class IB anti-arrhthymetics dissociate from the voltage gated sodium channels?
Rapidly dissociate/unblock
How does the action of Class IC anti-arrhythmetics differ to Class IB?
Give an example of a Class IC anti-arrhythmetic:
The rate of Na+ ion influx is slowed much more strongly than class IB
So depolarisation occurs later than with Class IB (Lidocaine)
Example = Flecainide
What interval do the Class IC anti-arrhythmic drugs affect but this interval is impacted much less than Class IB since the Na+ ion influx happens sooner?
QRS interval prolonged with Class IC
What is not affected on an ECG with Class IB anti-arrhythmics but IS with Class IC?
Why is this the case?
QRS interval
The Class ICs delay the upstroke of the QRS way more than Class IBs (class IBs dont prolong it enough)
What part of the heart do Class II (beta blockers) target/bind to?
SAN
How do Class II anti-arrythmics affect the heart?
(Beta blockers)
Decrease the gradient of the funny current (since blocking the B-adrenoceptors reduces sympathetic tone and so inversely increases parasympathetic tone) = slower heart rate
Decreased uptake of of Calcium (leads to weaker contractions)
What is an example of a Class II anti-arryhthmic?
Beta blocker
Bisoprolol
Atenolol
What type of anti-arrhythmic is a Class III anti-arrhythmic?
K+ Channel blocker
What is the best example of a Class III anti-arrhythmic? (K+ channel blocker)
Amiodarone
What part of the heart do Class III K+channel blockers affect?
Cardiac myocytes
What is the effect of Class III anti-arrhythmics (K+ channel blockers) on the action potential cycle?
Prolongs repolarisation (by preventing the K+ efflux)
What interval on the ECG do Class III K+ channel blockers affect?
What is an example of a Class III anti-arrhythmic?
Prolongs the QT interval
Since it prolongs repolarisation
Amiodarone
What are 2 examples of Class IV anti-arrhythmics?
What type of drug are these?
Calcium channel blockers (Non dihydropyridines)
Verapamil = phenylalkylamine
Diltiazem = benzothizapine
What part of the heart do Class IV (Ca2+ channel blockers) target?
SAN
+
Cardiac myocyets
So affects pacemaker potential
How do Class IV anti-arrhythmics work?
What are 2 examples?
SAN:
Block L-type voltage gated Ca2+ channels
This slows the speed at which the depolarisation/upstroke happens once the threshold potential has been reached
Cardiac myocytes:
Blocks the L-type voltage gated Ca2+ channels which prolongs the plateau phase due to the Ca2+ channel blockade
Verapamil
Diltiazem
How do Class IV calcium channel blockers prolong the plateau phase in cardiac myoctes?
Reduced rate of influx of Ca2+ leads to a decreased rate of efflux of K+ which leads to a prolonged plateau phase
Which class of drug prolongs the QT interval?
What is an example of this drug?
How does it do so?
Class III (K+ channel blocker)
Amiodarone
Blocks the K+ channels slowing down/prolonging repolarisation
Repolarisation is the QT interval
What drug class causes QRS prolongation?
How does it do this?
What is an example?
Class IC
Delays QRS upstroke (Na+ influx) from happening lenghthening the QRS interval
What is represented by the PR interval?
The time taken for the AV node to conduct the electrical impulse from the atria to the ventricles
What classes of anti-arrhythmics prolong the PR interval and so work at the AV node?
Beta blockers (Class II)
Calcium Channel blockers (Class IV)
What is the negative effect of Amiodarone (Class III) prolonging the QT interval?
Can induce arrhythmia
By prolonging the QT interval/repolarisation time too much you increase the risk of getting early after depolarisations and so arrhythmias
What are 3 examples of anti-arrhythmic medications that dont fit in the 4 classes?
Digoxin
Ivabradine
Adenosine
These are considered Class V drugs (miscellaneous)
What class of drug is Digoxin?
Cardiac glycoside
How does digoxin work as an anti-arrhythmic drug?
AV node blockade (slows AVN transmission)
Stops the Na+/K+ ATPase leading to activity of the Na+/Ca2+exchanger to cease so levels of Ca2+ in the cells increase increasing the strength of contraction (+ve inotropy)
What is digoxin typically used for?
Heart failure
Arrhythmias
How does Ivabradine work as an anti-arrhythmic?
Slows heart rate
Inhibts the pacemaker current at the SAN so slows the rate at which the threshold potential is reached slowing heart rate
When is Ivabradine typically used?
Angina
Coronary disease
Arrhythmias
How does Adenosinei work to treat arrhythmias?
Stimulates A1 adenosine receptors at the AV node blocking the AV node preventing/reducing impulse travelling from atria to ventricles
This reduces rate of contraction of ventricles
What is adenosine typically used to treat?
Supraventricular tachycardia when the heart is beating extremely fast to the point you cant see what the atria are doing on an ECG
How long does adenosine last for as an anti-arrhythmic?
Couple seconds (very short lasting)
What is a contraindication of using class I anti-arrhythmics like Flecainide?
Structural heart diseases (changes that occur following MI) since it increases risk of arrhythmias
What is a contraindication of using Class II anti-arrhythmics?
Consider alternate treatments like CCB (verapamil or diltiazem) if ASTHMATIC
Don’t prescribe with Diltiazem or verapamil
Why shouldn’t you prescribe Class II anti-arrhythmias with diltiazem or verapamil?
Beta blockers also work on the SAN like the calcium channel blockers (non-dihydropyridines) verapamil and diltiazem
What is a contraindication for using class IV anti-arrhythmics (CCB)?
HFrEF
What are the negative side effects/adverse effects of Class III anti-arrhythmics like Amiodarone?
Hepatotoxic
Lung fibrosis
Optic neuritis
Thyroid toxicity
Peripheral neuropathy
What is a very effective drug for putting the heart back into sinus rhythm?
Amiodarone
What are the 2 general ways we get arrhythmias?
Generate abnormal impulses (ventricular ectopics)
Or
Conduct impulses abnormally (heart block, re-entry loops or accessory pathways)
What is atrial fibrillation?
Irregularly irregular contractions/electrical activity of the atria
What are the 2 methods by which you can try and stop an atrial fibrillation?
Rate control
Rhythm control
What is meant by rate control for trying to treat Atrial fibrillation?
Slow the rate of transmission from atria to the ventricles
What is meant by rhythm control for trying to treat Atrial fibrillation?
Stop the abnormal rhythm
If we are trying to reduce rate of excitation in atrial fibrillation, what heart structure do we need to target?
AV node (needs blocking)
What are some drugs that can block the AV node to control rate for Atrial fibrillation?
Adenosine (TOO SHORT LASTING, Afib will come back)
CCB (depending on HF status)
B-Blocker (depends on asthma status)
Digoxin (depends of exercise tolerance, lots of exercise people don’t tolerate well)
What drugs can be used to terminate the rhythm of Atrial Fibrillation?
Flecainide
Amiodarone
Sotalol
Cardio version
What type of control, rate or rhythm is best for treating an atrial fibrillation?
Young = rhythm control
Most = rate control
What class of anti-arrhythmic is sotalol?
Class III not Class II