 Hello and welcome to Physiology Open, for this video try to solve this question. In this question there are two statements. First statement is an assertion and the second statement is the reason for the first statement. Now you have to choose from the following five options. You can pause the screen and think about the answer. By the end of the video we will see whether you got the answer right or not. Let us see what are the classes of anti-arhythmic drugs. There are four classes of anti-arhythmic drugs depending on which channels or receptors they block. Class 1 drugs block sodium channels. Class 2 drugs are beta blockers. Class 3 drugs block potassium channels while class 4 drugs are calcium channel blockers. Let us see what will be the effect of these drugs on action potential of cardiac pacemaker cells as well as contractile cells. See this diagram is showing the action potential of both pacemaker cells as well as contractile cells. Pacemaker action potential has an automatic drift of resting membrane potential to the threshold which occurs due to opening of HCN channels and T type calcium channels causing entry of sodium ions and calcium ions respectively into the cells. This is phase 4 of action potential of pacemaker cells. By contrast you see in contractile cells this phase 4 is constant right. Now phase of depolarization or phase 0 is due to entry of calcium in pacemaker cells while it is due to entry of sodium in contractile cells. Phase of repolarization is due to exit of potassium from the cells in both contractile as well as pacemaker cells. In addition contractile cells have this plateau phase which is due to balance between entry of calcium and exit of potassium. Anyways for the action of the anti-arhythmic drugs we will not bring in this plateau phase again. So we will restrict ourselves to this phase 4, phase 0 of depolarization and phase 3 of repolarization. Also see the diagram of atrial action potential versus the diagram of action potential of ventricles. Now both are contractile cells yet there is some difference in their action potentials. See the duration of action potential of atrial cells is much less compared with that of ventricles. Tachy arrhythmias occur due to abnormality in either generation of action potentials or in conduction of impulse or maybe both. In short it can be addressed at the level of electrical activity in heart. So we should know first where on these action potential different class of anti-arhythmic drugs will act. Sodium xanol blockers that is class 1 anti-arhythmic drugs can block this phase in contractile cells. So due to this action the threshold for phase 0 of action potential increases. Remember that at threshold lot of sodium channels open. So if they are blocked less channels will be available for opening. So threshold will increase. Also it will decrease the slope of phase 0 it will not be this steep so it will cause slowing of the depolarization. Note that they won't affect the action potential of face maker cells it is being caused by calcium right. So these sodium channel blockers will affect the contractile cell's action potential. Class 2 drugs are beta blockers they will act here. On phase 4 of face maker action potential normally sympathetic activity increases the slope. So if we block this sympathetic activity phase 4 will become less steep something like this. Ultimately decreasing the number of impulses which are generated. Class 3 drugs that is potassium channel blockers will act here for both these action potential on phase 3. So the potassium ions will not be able to go out of the cells that is it will take longer time for the membrane to repolarize. Thus they will increase the duration of action potential and keep the cells retracted for longer time. Class 4 drugs on other hand act here in phase 0 of action potential of face maker cells. Remember they occur due to entry of calcium ions through calcium channels right. Now these are L type calcium channel blockers so they affect the phase 0 which is caused by opening of L type calcium channels. Before we go further we will talk little more about class 1 drugs. In class 1 there are 3 subclasses of drugs. See there are different states of sodium channels closed open and inactivated. At resting membrane potential they are closed as depolarization occurs they open and inactivate very fast and as repolarization occurs they again go back to closed state from inactivated state. So class 1 drugs are further classified into subclasses on the state in which the block sodium channels and how long it takes the channels to recover once they are blocked. This is known as the recovery time of the channels. Class 1A drugs block sodium channels in open state. Class 1B drugs block sodium channels in inactivated state and we have seen that sodium channels become inactivated after opening once depolarization occurs. So these class 1B drugs are most effective on an already depolarized tissue as seen in ischemia. Class 1C drugs block sodium channels in open state and also prolong the recovery time of these channels. So they will take long time to recover from the effect of the drugs. Plus these class 1A drugs they also have some effect on potassium channels. They also block potassium channels. So they have combined class 1 and class 3 activity. Okay now let us see the logic of treating tachyarythmias which occur due to different mechanisms. Hopefully you know about the various mechanisms which lead to tachyarythmias. If not you can check out the video given in the description section below. Well we will recap a little the physiological basis of arrhythmias while discussing which class of drugs may be used for treating them. Tachyarythmias may occur either due to enhanced automaticity, triggered automaticity or due to re-entry mechanisms. In arrhythmias due to enhanced automaticity the slope of the pre-potential becomes steeper. Maybe due to enhanced sympathetic activity or the maximum diastolic potential, this maximum negative potential becomes less negative. So that it can reach to the threshold faster. So how can these kinds of arrhythmias be treated? Basically you will want to decrease the rate of generation of impulse so that you can do either by decreasing the slope of this drift of phase 4. Right? Increasing the threshold for excitation. So phase 0 will start much above the usual threshold or by prolonging the action potential duration. So as action potential duration prolongs so automatically the number of impulses which will be generated will be less or maybe increasing the negativity of resting membrane potential so that it takes more time to reach to the threshold because the voltage change which it will have to cover to reach to the threshold will be much more. So now apply the action of classes of antirhythmic drugs. First option can be achieved by beta blockers. Second option can be achieved by blocking calcium channels in pacemaker cells or by blocking sodium channels for contractile cells. Remember that automaticity is restricted to pacemaker cells but sometimes in case of injury contractile cells also may assume the automaticity. Third option that is prolonging the action potential duration can be achieved by potassium channel blockers and fourth option that is making the membrane more negative potential can be done by acetylcholine and adenosine. Now these drugs are not given in any classes but they can make the membrane potential more negative. Note one thing here that in arrhythmias due to ectopic foci where contractile cells have the automaticity especially in case of ischemia we need to block sodium channels. Class 1B drugs which block the channels in inactivated state are more useful for ventricular ectopic foci especially in the systemic condition. Well see these are diagrams showing action potential of ventricles in atrium. We have said earlier also that duration of action potential of atria is much less than that of the ventricles right. That means in ventricles the channels remain inactivated state for longer time right. As channels change their state the drugs will dissociate from them so the drugs will be active only till the time the channel is in that state. That means these drugs will be more effective for ventricular arrhythmias because of ventricular action potential channels are in inactivated state for longer time. Class 1B drugs on the other hand are used for atrial fibrillation. Now let's come to second type of arrhythmias that is arrhythmias due to triggered automaticity. These arrhythmias occur due to after depolarizations which are seen either when action potential is prolonged that is early after depolarization or due to increased intracellular calcium load that is delayed after depolarization. So logically what will you want to do? First thing do not allow these depolarizations to occur right. Secondly if they develop do not allow up stroke of the action potential to happen. For preventing the development of early after depolarization we need to shorten the action potential duration because these occur and action potential duration is prolonged. For this increasing the heart rate by isoprateron infusion is recommended. Again we have not seen in the classes but here in this video we are talking about the strategy of treatment. So when we increase the heart rate the duration of action potential decreases. For preventing the development of DADs delayed after depolarization we need to decrease the intracellular calcium load that is do not allow calcium ions to enter the cells. So now apply the action of classes of anti arithmic drugs. For this we can use class 4 drugs that is calcium channels occur since calcium is responsible for DAD or even class 2 drugs because generally intracellular calcium load increases due to adrenergic stress. There exists a full mechanism by which adrenaline can cause increase in intracellular calcium but that is not the subject of this video. For the second part that is for preventing the up stroke of action potential you can block sodium channels and increase the threshold for generation of action potential right. So class 1A drugs again may be used for this. Now let's move to third type of earlier. These are the ones which occur due to reentry mechanisms. Reentry of impulse may occur when it has two conducting pathways but they differ electrically with one pathway slower and the other pathway having fast conduction and total time for the impulse to move around this reentry circle has to be longer than the time for the cells to recover from previous refractory period. So if the impulse takes time t1 to reach these cells here and the cells are refractory for time t2 t1 should be greater than t2 otherwise the impulse will find the cells refractory and it cannot be propagated further. So what can you do to treat this error? Simple keep the cells refractory for longer time so that this t2 becomes greater than t1. Again you put the drugs now you have to use the drugs depending on the cells which are involved in the pathway. So in case of ventricular cells block sodium channels and prolong their recovery time so class 1C drugs may be used. We have seen that they also prolong the recovery time of the channels. Also if you block potassium channels it will prolong the duration of action potential preventing it from getting repolarized. So if the cells are not getting repolarized sodium channels are in inactivated state and this is responsible for the cells being refractory to any stimulus. If in the reentry mechanisms AV node conducting pathway is a part of this reentry we have to use class 4 drugs calcium channel blockers because sodium is not involved in their action potential right? So calcium channel blockers will prolong their refractoriness. Class 2 drugs also prolong AV node refractoriness. Now let's come back to our original question. In this question the reason statement is correct. We have seen that potassium channel blockers do prolong the duration of action potential since they will delay repolarization. Assertion statement is also correct here. In reentry trachea ridnias we want to prolong the duration of action potential. So that cells are refractory for longer time right? But also if action potential is prolonged it may lead to development of early after depolarization. Thus these drugs though are useful for one type of aridnias predisposed to other type of aridnias. So in this case answer is that both the statements are true and indeed R is the correct explanation for A. So first option is the correct answer. In the next part in aridmia series we will be discussing aridmia treatment from a different point of view. Okay. Thank you for watching the video. If you like the video please subscribe to the channel till geology opens. Thank you.