Pharmacology 3 - Anti-Arrhythmic Drugs Flashcards
Which three tracts can travel within the heart from the SA node to the AV node?
- Anterior intermodal tract
- Middle intermodal tract (of Wenchenbach)
- Posterior intermodal tract (of Thorel)
Which tract conducts the action potential from right to left atria?
Bachmann’s bundle
What are the two main causes for defects in impulse formation?
- Altered automaticity
- Triggered activity
Altered automaticity can occur in which two ways?
- Physiologically - the ANS can provoke sinus tachycardia or sinus arrhythmias
- Pathological - A latent pacemaker can take over from the SA node
What is overdrive suppression?
This is the control, or dominance, the SA node exerts over latent pacemakers by firing the fastest and most regularly
How can the actions of a latent pacemaker manifest themselves?
- Escape beats
- Escape rhythm - series of escaped beats
What is an ectopic beat?
A heart beat initiated by an impulse originating out with the SA node
What is an ectopic rhythm?
A series of ectopic beats
What is triggered activity?
This is when normal action potentials can trigger abnormal action potentials, or afterdepolarisations
What are the two types of triggered activity (or after depolarisation)?
- Early afterdepolarisation - often in Purkinje fibres
- Delayed after depolarisation
When will an early afterdepolarisation occur?
Between phases 2 and 3
Why does an early afterdepolarisation cause an escape rhythm?
One early after depolarisation will lead to another
Which type of drugs will cause early afterdepolarisations?
Drugs that prolong the QT interval
(beta blocker, sodium channel blocker)
Sotalol is an example
When will a delayed afterdepolarisation occur?
After a full repolarisation of ventricular muscle
Why does a delyaed afterdepolarisation occur?
The normal action potential is followed by a depolarisaing event which may cause another action potential
This is associated with calcium overload provoking a transient inward sodium current
What may be the cause of a delayed after depolarisation?
Catecholamines, digoxin and heart failure
Impulse conduction can be affected mainly by which three factors?
- Re-entry
- Conduction block
- Accessory tracts
What is anterograde conduction?
Normal conduction
When an action potential reaches a non-excitable region, the action potentials will cancel each other out at the points at the other side of this region preventing recirculation of the impulse around this region
What is re-entry?
Retrograde conduction - circus movement
A self sustaining circuit around a non excitable region
This is caused by a unidirectional conduction block either side of the non-excitable region
Cancellation will not occur and one impuls ewill be able to constantly circulate the non-excitable region
In order for re-entry to occur, what feature must be true of the retrograde action potential and why?
It must be slow
This ensures that the first impulse has caused stmulation and had been through its refractory period and is ready to be stimulated again.
Otherwise the myocardium will not be ready to be restimulated
What are the two types of conduction block?
- Partial
- Complete
Conduction block affects which area in the heart?
AV node
What is first degree block?
The PR interval is abnormally long, but is still followed by a QRS complex
Second degree block includes which two forms?
- Mobitz type 1
- Mobitz type 2
What is Mobitz type 1?
PR interval increases progressively until a QRS complex is missed
This leads to a missed ventricular beat
What is Mobitz type 2?
Every nth impulse fails to get through the AV node
Usually rhythm is maintained
What is third degree heart block?
This is complete heart block
The atria and ventricles beat independently
Ventricles rely on latent pacemakers (usually in Purkinje fibres)
Third degree heart block will usually result in what?
Reduced cardiac output and bradycardia
Why does third degree heart block often result in irregular and less reliable heart beats being produced?
The Purkinje system releases impulses slower and less reliably
Give the name of the additional (accessory) pathway that can bypass the AV node which is only present in some individuals
Bundle of Kent
Why do impulses spread to the ventricles much mre quickly to the ventricles via the bundle of Kent versus the AV node?
The bundle of Kent has much less resistance
Name a common condition involving accessory tracts
Wolff-Parkinson-White syndrome
What are the four classes of anti-arrhythmic drugs?
- Voltage activated sodium channels
- Beta-adrenoceptor antagonists
- Voltage activated potassium channels
- Voltage activated calcium channels
How do class I anti-arrhythmic drugs function?
Block voltage activated sodium channels
This prevents the upstroke of the action potential (phase 0)
Why are there three subsets of the class I anti-arrhythmic drugs?
This is due to the different rates at which the drug binds and unbinds to sodium channels
Which variants of class 1 anti-arrhythmic drugs bind and unbind:
a) Rapidly to sodium channels
b) With moderate speed to sodium channels
c) Slowly to sodium channels
a) Class 1b
b) Class 1a
c) Class 1c
Give an example of a class 1a antiarrhythmic drug
Disopyramide
Give an example of a class 1b antiarrhythmic drug
Lignocaine
Give an example of a class 1c antiarrhythmic drug
Flecainide
Anti-arrhythmc drugs (class II) will bind to what?
Beta adrenoceptors
Give an example of a class 2 antiarrhythmic drug
Metoprolol
Anti-arrhythmic drugs (class 3) will bind to what?
Potassium channels
Give an example of a class 3 antiarrhythmic drug
Amiodarone
Anti-arrhythmic drugs (class 4) will bind to what?
Calcium channels
Give an example of a class 4 antiarrhythmic drug
Verapamil
In which three states do volatge activated channels exist?
- Resting
- Open
- Inactivated
In which state is it particularly undesirable to block voltage activated channels?
Resting
This means they cannot be activated by depolarisation
Normal heart cycle would be disrupted
Why do class 1 anti-arrhythmic agents not bind preferentially to volatge activated channels in the resting state?
They instead bind preferentially to channels in the open or inactivated state
This is to block or stabilise the channels respectively
In high frequency firing, which state do voltage activated channels spend a lot of time in?
Open
Describe the statement:
“Class I agents bind in a use-dependent manner”
Class I agents bind preferentially to the open state of voltage activated channels
The more time the channels spend in this state, the more the class I agent will be utilised
This means class I agents will not disrupt normal beating frequencies and will target the faster frequencies
How can class I anti-arrhythmic agents effect the inactivated state and what does this mean?
It is stabilised so lasts for longer
This reduces the frequency of action potentials in the heart
How do class I anti-arrhythmc drugs cause harmony of myocyte beating?
- They block channels firing too fast
- They stabilise all channels in the inactivated state increasing the length of this state
- They dissociate in the resting state allowing all myocytes to be “released” again at the same time which allows for a “fair” start
Why do class I anti-arrhythmic agents act preferentially on ischaemic tissue?
- There is more time for the agents to act to block channels (the action potential is of a longer duration)
- The rate of channel recovery from block is decreased
Adenosine is a drug used to treat which types of arrhythmia?
Supraventricular arrhythmia
How does adenosine function?
- Blcoks AP propagation through AV node
- Works on G protein coupled adenosine receptor which can activate GIRK channels
- This hyperpolarises the AV node preventing APs from getting through
How long does adenosine function and what does its administration aim to achieve?
- 8 - 10 seconds
- Terminate paroxysmal supraventricular tachycardia (due to re-entry)
How does digoxin function and what is it administered for?
It supresses AV node conduction by increasing the refractory period and dampens chaotic re-entrant impulses from travelling through the atrium
It will treat supraventicular arrythmias
Verapamil is what class of anti-arrhythmic agent?
Type IV
How does verapamil function?
- Slows conduction and prolong refractory period in AV node and bundle of His
- It blocks L-type calcium channels responsible for plateau
- This means contraction is less forceful and last for a shorter length of time
- This will block chaotic re-entrant impulses through the atria which may be conducted into the ventricles
What is verapamil used to treat?
Atrial flutter and atrial fibrillation
Lignocaine is used to treat what?
Ventricular arrhythmias
How does lignocaine function?
- It causes rapid block of voltage activated sodium channels
- Inactivated channels are stabilised
- Rapid unblocking occurswhich will affect primary sodium channels that discharge potentials at a high rate
When is lignocaine most used?
Ventricular arrythmias following MI
High does of verapamil can cause ______ _______
Verapamil should never be used in conjunction with ______ _________
Heart block
Beta blockers
Disopyramide or procainamide are which class of anti-arrhythmic agents and what are they used to treat?
Class Ia
Ventricular arrythmias (recurrent)
How do disopyramide and procainamide function?
- Open sodium channels (volatge activated) are blocked
- They act by a use-dependent mechanism
- When action potential release is high, the moderate rate of unblocking is too slow to maintain the AP release
- This forces AP release to slow
What type of agent is flecainide and how does it function?
Type Ic
- Slow rate of block/unblock of sodium voltage activated channels
- This strongly depresses conduction in myocardium and reduces contractility
What is flecainide used to treat?
Paroxysmal atrial fibrillation
What is the dowside to flecainide?
It has a negative ionotropic effect and could potentially induce serious ventricular arrythmias
What type of agents are propranolol and atenolol?
Type II anti-arrhythmic drugs
Beta blockers
Type II anti-arrhythmic agents work in which way?
They supress impulse conduction through the AV node
This supresses excessive sympathetic drive which could potentally trigger ventricualr arryhthmias
Type II anti-arrhythmic agents can treat what?
Supraventricular tachycardia
Amiodarone and sotolol are which class of anti-arrhythmic agent?
Type III
How do type III anti-arrhythmic agents function?
- They slow repolarisation of action potential by blocking volatge activated potassium channels
- This increases action potential duration and refractory period
- They will supress re-entry
Why is amiodarone special?
It is effective against SVT and VT because it has properties of:
- Class Ia
- Class II
- Class IV
It can also block beta adrenoceptors
When would amidarone be used?
It reduces mortality after MI and congestive heart failure
What are the side effects of long term amiodarone use?
- Pulmonary fibrosis
- Thyroid disorders
- Photosensitivity reactions
- Peripheral neuropathy
