[Music] welcome to this presentation on class 3 and class 4 antiarrhythmics after this session you should be able to describe the usage and effects of class 3 antidysrhythmics agents that widen duration of the action potential and class 4 antiarrhythmics also known as calcium channel blockers you should also be able to outline how class 3 antiarrhythmic agents and calcium channel blockers may affect your practice and the patient's cardiac status and care let's review the cardiac cell properties and the action potential contractility is the ability of the cardiac cell to shorten and return to the original length in response to an electrical impulse calcium is required for this to take place automaticity is the ability of the cardiac pacemaker cells to depolarize spontaneously calcium is also required for this to take place as well excitability is the ability of resting polarized cardiac cells to depolarize in response to an electrical impulse and conductivity is the ability of all cardiac cells to conduct electrical impulses to the adjacent cardiac cell in this presentation we will focus on class 3 antiarrhythmics and their effect on the myocyte action potential as well as class 4 calcium channel blockers and their effect on pacemaker action potentials in this slide the effects of class iii antiarrhythmics on myocyte action potential is shown class 3 agents widen the duration of the myocyte action potential class iii agents include amiodarone dronetarone bertillium along with the beta blocker sotalol because it has some class 3 properties class 3 anterior rhythmics affect the repolarizing potassium currents and thus markedly widen the duration of the action potential this next slide looks at the effect of class iii drugs on purkinje cell action potentials also known as myocyte action potentials when the action potential duration is widened this increases the effective or relative refractory period of the action potential the result is that the action potential is no longer able to receive and depolarize in response to an impulse such as in the case of re-entry rhythms this is the desired effect of these agents in addition to widening the action potential duration and the effect of refractory period the class iii drugs amiodarone androneterone also decreases conduction velocity and decreases the rate of firing therefore decreasing automaticity of pacemaker cells this is only true of amiodarone androneterone furthermore because class 3 agents lengthen the action potential duration and ultimately prolong repolarization lengthening of the qt interval can result on the ecg this can predispose patients with hypokalemia hypomagnesemia and pre-existing bradycardia to have life-threatening arrhythmias such as torsad depois a particular form of polymorphic ventricular tachycardia shown in the image below next we will discuss the class iii agent amiodarone amiodarone lengthens the action potential duration resulting in lengthening of the effective refractory period in all cardiac tissues including accessory pathways amiodarone has both class 3 properties for lengthening the action potential and class 1a properties as a potent sodium channel blocker the result is a depression of the myocardial and his purkinje conduction system mild vasodilation a negative chronotropic and mild negative inotropic effects ultimately these actions alter the ecg by widening the pr interval qrs interval and qt interval indication for the use of amiodarone is to treat refractory life-threatening ventricular tachycardia and atrial fibrillation it is given both intravenously and orally adverse effects of amiodarone are torsade depoint rashes photosensitivity pulmonary fibrosis thyroid disease and skin discoloration sotalol has class 2 beta blocker properties that result in sinus and av node depression sotalol also has class 3 properties of lengthening action potential duration in atrial and ventricular muscle cells sotolol is indicated for the maintenance of sinus rhythm post-electrical cardioversion and in recurrent atrial fibrillation and atrial flutter it is also indicated to treat and prevent life-threatening ventricular arrhythmias such as sustained ventricular tachycardia ventricular fibrillation and arrhythmias refractory to any other antiarrhythmic agents solol is only given in oral form adverse effects of sodalol include life-threatening ventricular arrhythmias such as torsades depoint when it is used in combination with other potassium wasting diuretics or other drugs that cause hypokalemia or prolong the qt interval the adverse effects of sodalol's class ii properties are bradycardia and bronchospasm ebutylide is a class iii agent that prolongs action potential repolarization by activation of a slow inward sodium current in addition to blocking the rapid component of the delayed rectifier potassium current during repolarization it is used to convert atrial fibrillation or atrial flutter to normal sinus rhythm adverse effects of this class iii agent also include torsad depoint which can be precipitated when used in conjunction with potassium wasting diuretics or other agents that cause hypokalemia or prolong the qt interval dophetolide is similar to ebutylide in that it prolongs repolarization by inhibiting only the rapid component of potassium current it has a mild negative chronotropic effect and is used only in the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm because dophelide can cause life-threatening ventricular arrhythmias it is recommended that it should be reserved for patients in whom atrial fibrillation or atrial flutter is highly symptomatic therefore it is not for use in paroxysmal atrial fibrillation adverse effects include torsade depoint among other life-threatening ventricular arrhythmias it is given only in oral form slide 14 vernaculant blocks the rapid component of the potassium rectifier current but it is more selective for the ultra-rapid potassium current which is mainly found in the atria as such vernacalant is more selective for atrial tissue than ventricular tissue it exhibits rate-dependent slowing meaning the faster the heart rate the more potent the drug is at slowing down heart rate since it has a short half-life it is only given intravenously and is used only in the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm in addition to the usual life-threatening ventricular arrhythmias vernaculant can cause low blood pressure altered taste and sneezing let's take some time to check some of the concepts we've covered pause the lecture and think about the question before moving on how do class 3 antiarrhythmics work to treat reentry rhythms such as afib class 3 antiarrhythmics work by prolonging the repolarization phase which increases the effective refractory period preventing reentry rhythms from firing next we will focus on class 4 antiarrhythmics also known as calcium channel blockers the image here represents class 4 agents calcium channel blockers and shows its effects on the pacemaker action potential drugs we will be discussing include varapamil and diltiazem recall from previously that calcium is required for contractility and automaticity to take place with regards to class 4 calcium channel blockers we are concerned with automaticity and contractility as these are the cell properties affected by calcium channel blockers class iv agents are calcium channel blockers or antagonists there are two categories of calcium channel blockers they are dihydropyridines and non-dihydropyridines dihydropyridine include the drug nifedipine amlodipine and phylodipine this group's generic names end with the suffix peen non-dihydropyridines include deltiazem and verapamil take note that dhps do not affect myocyte or pacemaker action potentials whereas non-dhps prolong pacemaker or nodal action potential in general calcium channel blockers work by blocking the l channel and t channels that calcium normally passes through the l channels are long lasting open calcium channels and are positively affected by an increase in catecholamines these are the main channels where calcium channel blockers work t channels are more transiently open channels and the exact role of calcium channel blockers on this channel is unknown calcium channel blockers also block entry of calcium in both smooth muscle and myocardium to varying extents this results in less calcium available for the contractile process of muscles and has a vasodilatory and negative inotropic effect here we will discuss the two groups of calcium channel blockers each group binds to different sites on the calcium channel pores the group dhp or dihydropyridine have greater vascular selectivity this results in a modest negative inotropic effect due to the unloading effect of peripheral vasodilation this group is primarily used to treat hypertension the next group non-dhp or non-dihydropyridines are responsible for nodal inhibition which results in a decrease in heart rate because they affect pacemaker action potential their action resembles that of beta blockers and they are primarily used for supraventricular arrhythmias but can be used to treat hypertension also these agents can prolong the pr interval this slide shows the classification of calcium channel blockers they are listed in their groups the channels that they affect the action in the heart and the names of the drugs accordingly group one consists of dihydropyridines or dhps these are l-channel blockers that affect calcium into vascular smooth muscle resulting in vasodilation these drugs are used to treat these drugs include nifedipine amlodipine and felodipine group 2 are l channel blockers with some possible t-channel blockade they inhibit the firing of the sa and av node causing a decrease in automaticity of those pacemaker cells this group includes the non-dihydropyridine or non-dhps deltiazem and verapamil since calcium channel blockers have an effect on vascular smooth muscle resulting in vasodilation this places them in the category of vasodilator drugs calcium channel blockers are considered arterial vasodilator drugs which primarily decrease afterload and thus increase cardiac output as well as decrease hypertension let's take a look at calcium channel blockers and oxygen supply and demand since the goal of pharmacological therapy is to balance oxygen supply and oxygen demand it is important to understand how drugs affect these factors that determine oxygen supply and demand calcium channel blockers decrease automaticity and heart rate decrease blood pressure and decrease contractility all of these factors decrease oxygen demand calcium channel blockers cause dilation of coronary arteries which improves blood flow to the heart and thus increases oxygen supply to the heart calcium channel blockers also cause vasodilation decreasing peripheral vascular resistance increasing cardiac output and oxygen supply indications for the use of calcium channel blockers include stable angina because of their effect on oxygen supply and demand coronary artery spasm hypertension and supraventricular arrhythmias though this is for varapamil and deltaism only calcium channel blockers are contraindicated in the setting of an acute myocardial infarction unstable angina bradycardias and av blocks adverse effects include hypotension bradycardia av block congestive heart failure constipation peripheral edema headache and flushing of the skin now let's take a look at the drugs individually nifedipine a dhp calcium channel blocker is a powerful vasodilator and provides a mild negative inotropic effect it interacts with grapefruit juice and grapefruit resulting in decreased clearance of nifedipine it is indicated to treat vasospastic angina hypertension and raynaud syndrome contraindications include arrhythmias heart failure with reduced left ventricular ejection fraction bradycardia av blocks and sick sinus syndrome amlodipine a dhp calcium channel blocker is a vasodilator it is indicated to treat vasospastic angina hypertension and reynod syndrome it is recommended to reduce the dose in elderly patients contraindications include severe liver dysfunction it is not useful in treating arrhythmias and like all calcium channel blockers it is not effective for treating heart failure phylodepene a dhp calcium channel blocker is also a vasodilator it is indicated to treat hypertension reduce the risk of stroke in hypertensive patients and to treat raynaud syndrome it is also recommended to reduce the dose in elderly patients and those with liver dysfunction it interacts with grapefruit and grapefruit juice just like nifedipine and amlodipine it has similar contraindications as nyphetipine diltiazem a non-dhp decreases sa node and av node automaticity it also causes some moderate dilation of arteries deltaism has a greater effect on the sa node than varapamil does however it has a lesser effect on the av node than verapamil by decreasing the heart rate diltiazem also decreases the rate pressure product at any given level of exercise it is used to treat angina hypertension and supraventricular arrhythmias it is contraindicated for use in patients with heart failure sick sinus syndrome av blocks and hypotension varapamil a non-dhp calcium channel blocker is a moderately potent vasodilator which has a marked negative ionotropic effect and also causes mild depression of sa node function and av node conduction it is indicated for the treatment of angina hypertension and supraventricular arrhythmias it is contraindicated for use in bradycardia sa node and av node disease heart failure acute myocardial infarction hypotension and wolf parkinson white syndrome this last slide is a table that summarizes the effects of calcium channel blockers on various locations in the heart a single plus indicates a mild effect a double plus indicates a moderate effect and multiple plus signs indicate a significant effect on the area of the heart before we end the session let's reflect on the difference between dhp and non-dhp calcium channel blockers why are dhp calcium channel blockers preferred in the treatment of hypertension over non-dhp calcium channel blockers dhp calcium channel blockers have greater vascular selectivity reducing afterload more than non-dhp calcium channel blockers making them preferred in hypertension over non-dhp calcium channel blockers that takes us to the end of this presentation on class 3 agents and calcium channel blockers [Music] you