Anti-arrhythmic drug pharmacology

Question 1

What is a cardiac arrhythmia?

Answer 1

An arrhythmia is a problem with the rate or rhythm of the heartbeat.

During an arrhythmia, the heart can beat too fast , too slow or with an irregular rhythm.

Question 2

What does an ECG do?

Answer 2

It is recording the total electrical activity of the heart.

You can also map the electrical activity of a single cardiomyocyte in the ventricles and we can see that the QRS complex is associated with the main depolarisation event of the ventricular cardiomyocyte and the repolarisation is associated with the T wave.

Question 3

What are the Class 1 antiarryhythmic drugs of the Vaugham Williams classification?

Answer 3

Na+ / Sodium Channel Blockers

• There are 3 different types of these A,B and C

Question 4

What are the Class 2 antiarryhythmic drugs of the Vaugham Williams classification?

Answer 4

Beta Blockers

• They will extend the firing so phase 4 will be longer and there will be less action potentials at a time/minute
• They predominantly work the SA node and they act on the pacemaker cell action potential not the cardiomyocyte action potential.
• The pacemaker action potential normally has a drift to threshold and the beta blockers will reduce the rate of this slow drift and therefore will extend this phase and this will lead to a lengthening of the time between action potential firings and this will serve to DECREASE THE HEART RATE.

Question 5

What are the Class 3 antiarryhythmic drugs of the Vaugham Williams classification?

Answer 5

K+ / Potassium channel blockers

• They work on the repolarisation step/ 3rd phase of the cardiomyocyte action potential
• Potassium is required for the repolarisation event and is pumped out of the cardiomyocytes via the rectifier
• Potassium channel blockers block these rectifier channels
• They will ultimately widen the action potential because you are slowing down the depolarisation of the cardiomyocyte and this will lead to an extension of the widening and duration of right action potential.

Question 6

What are the Class 4 antiarryhythmic drugs of the Vaugham Williams classification?

Answer 6

Calcium / Ca2+ channel blockers

• They function on the plateu phase of the cardiomyocyte action potential
• They block the calcium entry into the cardiomyocytes during the plateu phase.
• This will have an effect of reducing the forcer contraction
• It also works predominantly on the AV node as well so you end up slowing down the transmission of the action potential from the atria to the ventricles (AV node is the only point of conductivity ) so you will slow the spread of the action potential to the cardiomyocytes.
• Secondary effect: It will also affect the cardiomyocyte contraction, it will slow the rate of calcium getting in and therefore reduce the forcer contraction as well.

Question 7

What are the 2 Non-vaughan William antiarrhythmic drugs?

Answer 7

• Adenosine
• Digoxin

Question 8

What is Digoxin?

Answer 8

When treated with Digoxin, the cardio myocytes will inhibit the Na/K ATPase.

• So normally Na will be leaking into the cardiomyocyte and K will be leaking out of the cardiomyocyte.
• During the action potential there is an increase in Na+ in and K+ out of the cardiomyocyte in order to depolarise and depolarise the membrane.
• This Na/K ATPase pump normally restores the levels, so it will pump K+ back into the cardiomyocyte and pump Na+ out of the cardiomyocyte.
• This is only dependent because your fighting against concentration gradient so you require ATP hence the ATPase
• However if you inhibit this using Digoxin, you will increase the Na+ inside the cardiomyocyte.
• So theres too much sodium in the cardiomyocyte and normally the Na+/Ca2+ exchanger will exchange sodium for calcium. So normally it will pump sodium in and calcium out
• However when theres too much sodium in the cell, this reverses activity and will lead to pumping sodium out of the cardiomyocyte and calcium into the cardiomyocyte.
• This will then increase the intracellular levels of calcium which will lead to an increase in forcer contraction in the cardiomyocyte.
• Digoxin can be used to restore cardiomyocyte contractile function

Question 9

What is Adenosine?

Answer 9

Adenosine will normally bind to the receptor and this will reduce the firing at the sinus node.

• So it is working at the SA node, on the pacemaker cells
• So when Adenosine binds to the Adenosine1 (A1) receptor, the A1 receptor is coupled with the inhibitory Gi protein
• On binding of the A1 receptor to Adenosine, the Gi protein is released and this will inactivate adenylate cyclase which will lead to a decrease in cAMP production, which will then in turn lead to a decrease in the action potential firing in the pacemaker cells.
• This will serve to extend the time between action potential productions in the pacemaker cells in the SA node.