[Music] welcome to this presentation on Class 2 drugs beta blockers this session will be an introduction to the category of drugs beta blockers after completing this session you should be able to describe the usage and effects of Class 2 anti arhythmic beta blockers and outline how beta blockers may affect your practice and the patient's cardiac status and Care beta blockers according to Von Williams classification system are Class 2 agents on this slide you will see a diagram in the top right hand corner named Class 2 Beta blocking agents with a picture of the pacemaker action potential about them beta blocking agents primarily affect the action potential of the pacemaker cell which controls the heart rate let's review the cardiac cell properties and the action potentials contractility is the ability of the cardiac cell to shorten and return to the original length in response to an electrical impulse automaticity is the ability of the cardiac pacemaker cells to depolarize spontaneously 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 beta blocking agents and their effect on the pacemaker action potential with that in mind the cardiac cell property which will mostly be discussed is automaticity the ability of a cardiac pacemaker cell to depolarize spontaneously beta block agents are beta adrenergic receptor antagonists beta blockers indirectly block the current of a pacemaker cell and depolarizing current and the calcium channels by dampening adrenergic activation they do not have any effect on the action potential duration this includes all beta blocking agents with the exception of sodol in this slide you will see a diagram of the pacemaker action potential and how Class 2 anti-ar rithmic drugs also known as beta blockers affect the pacemaker action potential beta blocking agents decrease the slope of phase 4 which results in a decrease rate of impulse firing in terms of how it affects the cardiac cell property it decreases automaticity it can also have a prolonged repolarization effect of the AV node which results in an in increase of effective refractory period also known as the decrease in re-entry in order to understand how beta blockers work you must understand how beta receptors work beta receptors are located throughout the body and have different functions beta 1 receptors are located in the heart and in the re and secreting tissues of the kidney and parts of the eyes beta 1 receptors are limited in the bronchial tree in the lung beta 1 receptors in the heart are located in the SA node and AV node when beta 1 receptors are stimulated this causes an increase in heart rate conduction automaticity and contractility beta 2 receptors are located in the bronchial and Vascular smooth muscle gastrointestinal tract uterus insulin secreting tissues of the pancreas and our Lim lied in the heart and large coronary arteries beta 2 receptors in the lungs and the legs once stimulated cause phaso dilation of the arterials in sceletal muscle they cause Bronco dilation in the lungs increase intestinal motility and increase the breakdown of glycogen and lipids in related organs another type of receptors we need to discuss are alpha receptors once stimulated these receptors cause phasal constriction of most arterials in this slide we will discuss mechanism of action of beta blockers beta blocking agents block the beta adrenergic receptor thus preventing The Binding and activation of the receptor by catacol amines such as epinephrine and norepinephrine by blocking activation of this receptor beta blockers decrease heart rate automaticity myocardial contractility and velocity of cardiac contraction in the SA node this results in a negative chronotropic effect which lowers the heart rate in the AV node this results in a negative dromotropic effect which decreases conduction in The myocardium this results in the negative inotropic effect or decrease in contractility as a result result the use of beta blockers is anti-ischemic and anti- arhythmic beta blockers also indirectly act to inhibit funny current a pacemaker current that promotes Pro arhythmic depolarization in damaged heart tissues acts on the inward calcium current decreases rein release and enhances the effects of a Inhibitors in heart failure and Mi patients beta blockers can be further separated into first second and third generation agents the first generation results in non selective blockade of both beta 1 and beta 2 receptors and includes Propranolol nyol sodol timolol the second generation of beta blocking agents also known as beta 1 selective are bisoprolol metoprolol the tenolol and autol the third generation beta blockers have vasod dilator properties in addition to blocking beta 1 and or beta 2 receptors these drugs include carvol LOLOL and nebivolol by now you might notice that all the beta blocking agents end in the suffix L beta blocking agents are broken down into Generations based on their selectivity of which beta receptors they block for example first generation beta blockers are not cardiio selective blocking beta 1 receptors and beta 2 receptors blockade of beta 1 receptors results in a decrease in heart rate conduction automaticity and contractility they also block beta 2 receptors in the lungs and legs causing bronos spasm phasal constriction decreasing gastric motility and a decrease in blood sugar levels second generation beta blockers block chiefly beta 1 receptors in the heart resulting only in a decrease in the heart rate conduction automaticity and contractility this is called cardioselective third generation beta blockers cause vasod dilation in addition to blocking beta 1 and or beta 2 receptors they C cause vasod dilation either by blocking alpha 1 receptors or by promoting nitric oxide release resulting in vasod dilation of most arterials the indications for using beta blockers in arhythmia include rate control in atrial fibrillation inappropriate sinus tachicardia emotion or exercise induced paroxysmal atrial tachicardia exercise induced ventricular arhythmia congenital prolonged QT syndrome actual valve prolapse arhythmia thyrotoxicosis arhythmia foch chromosoma a tumor of the adrenal system that produces cacaman surges like adrenaline increased sympathetic beta adrenergic activity and severe recurrent ventricular tachicardia not esic in origin other indic ations for using beta blocking agents include ischemic heart disease acute myocardial infarction hypertension heart failure cardiomyopathy aortic dissection Marfan syndrome and diabetics at risk as well as anxiety essential tremor migraine prophylaxis and glaucoma contraindications for using beta blockers include conduction delay problems such as sick sinus syndrome or second or third degree AV blockade heart rate less than 60 beats per minute asthma chronic obstructive pulmonary disease and other bronos diseases severe peripheral vascular disease including rod syndrome decompensated class 4 heart failure severe cardal and patients with insulin dependent diabetes who are prone to hypoglycemia note that second generation beta blockers may also be used in moderate doses in patients with lung conditions because they are selective for the heart adverse effects of these agents are related to decreased sympathetic activation and thus include bronchospasm and respiratory distress central nervous system effects impotence and reduction of libido and nausea vomiting and epigastric distress additionally these agents May initially worsen heart failure and therefore should be avoided during acute decompensated heart failure let's take a moment to discuss beta blocker's oxygen supply and demand within the heart a goal in healthcare is always ensure the balance between oxygen supply and demand in in order to maintain balance throughout the body system beta blocking agents do this very well beta blockers decrease oxygen demand of the Heart by lowering the heart rate reducing the afterload decreasing contractility and decreasing oxygen wastage beta blockers increase oxygen supply in the Heart by increasing the time spent in diast thus increasing coronary artery profusion and causing less excise size Vaso constriction since we know the coronary arteries profused during the diast phase of the cardiac cycle and beta blockers increase the phase of diast by lowering the heart rate we can say that this increases oxygen supply specifically to the coronary arteries when you effectively decrease oxygen demand and increase oxygen supply the overall oxygen deficit caused by arhythmia and heart dis disease is reduced beta blockers are the firstline drugs in the treatment of angina and have been shown to reduce mortality abolish silent es schic attacks improve blood supply and block exercise induced tachicardia and vasil constriction target heart rate for beta blocker therapy in angina is 55 to 60 beats per minute at rest and no greater than 100 beats a minute during exercise beta blockers for the treatment of acute coronary syndrome are started early especially in presentation of hypertension and tachicardia the result is decreased myocardial oxygen demand and decreased esea the goal is to prevent unstable angina from turning into myocardial infarction beta blockers in use for acute myocardial inunction are given to patients early providing they have no contraindications present when given within 3 hours of an acute myocardial infection beta blockers have been proven to decrease mortality in the first seven days beta blockers are continued indefinitely for patients with residual left ventricular dysfunction beta blockers decrease mortality prevent recurrent Mi and heart failure beta blockers for the treatment of hypertension is an effect therapy for patients aged less than 60 years old or patients with additional compelling indications such as Mi or heart failure in hypertension or angina with LV dysfunction combining beta blockers and ACE inhibitors improves outcomes in heart failure overactivation of the sympathetic nervous system is detrimental beta blockers curb this sympathetic overactivation and are recommended for class 1:3 heart failure and for compensated class 4 heart failure beta blockers are used to treat arhythmia such as symptomatic ventricular premature beets also known as premature ventricular contractions or PVCs in Normal Hearts and coronary disease they are used in acute MI premature ventricular contractions and Es schia caused by camine surge they are also used to treat AV noal re-entry tachicardia atrial fibrillation as rate control agents peroperative supraventricular tachicardia or svts non-sustained ventricular tachicardia recurrent VT and recurrent ventricular fibrillation other indications for beta blocker therapy include elective percutaneous coronary intervention or PCI dissecting aortic aneurysm Marfan syndrome and diabetic patients with other compelling indications such as Mi aib or heart failure now let's discuss the specific beta blocker agents Propranolol is a beta blocker which is non-elective and has been used since 1964 it is an insoluble short acting drug that needs twice daily dosing it is contraindicated in heart failure patients with reduced ejection fraction as it was not found to reduce mortality three beta blockers that reduce mortality in heart failure are bopol metalol and corvalol it is also contraindicated in patients who smoke cigarettes as smoking lowers blood levels of this drug by producing enzymes that break down the drug adverse effects of propranolol include fatigue depression vivid dreams and memory impairment because it is lipid soluble and has high uptake in the brain autol is a relatively cardi selective agent which has mild intrinsic sympathomimetic activity and Mild membrane stabilizing activities cardiio selective means this this beta blocker mainly blocks beta 1 receptors it is moderately lipid soluble cardio protective and used to treat hypertension and to decrease postm mortality a tenolol is one of the first beta 1 cardio selective drugs with strong cardio selective properties it is lipid insoluble used in angina and for postm protection and to treat hyper tension blood levels of Atenolol are maintained in patients who are heavy smokers the drug has less cardioprotective features than other beta blockers the most pronounced adverse effects are sedation and fatigue bopol is a beta blocker which is highly beta 1 selective it is 50% lipophilic and 50% hydrophilic it is one of the three beta blockers in indicated for the treatment of class 1:3 heart failure as well as compensated class 4 heart failure it shows significant reduction in overall mortality for patients with heart failure and is used in combination with diuretics for hypertension it is more effective than older beta blockers in controlling hypertension esmolol is a short acting cardi selective beta blocker used for SVT and recurrent onset atrial fibrillation or atrial flutter a major adverse effect is hypotension this agent is contraindicated in cases of severe hypotension or cardiogenic shock carvol is a third generation beta blocker which blocks both beta 1 and beta 2 receptors as well as alpha 1 receptors its ratio of alpha 1 to beta 1 to Beta 2 blockade is as follows 1 to 10 to 10 as an alpha blocker Carvel causes increased phaso dilation and orthostatic hypotension compared to first and second generation beta blockers it is used to reduce mortality in patients with class 1 to3 and compensated class 4 heart failure it is also used in hypertension and angina it should be taken with food and may cause dizziness light-headedness or hypotension Le betalol is also a third generation beta blocker with an activity ratio for Alpha 1 to beta 1 to Beta 2 receptors as follows 1 to 7 to 7 it is used to treat hypertension and hypertensive emergencies and must be given two to three times per day more common adverse effects include dizziness Li headedness hypotension significant postural hypotension rash and impotence sometimes although rarely liver dysfunction is another adverse effect metoprolol is a second generation beta blocker with moderate cardio selectivity and is lipid soluble it can be used in patients with bronos disease at doses less than 150 migr a day it is used in post Mii therapy to decrease the incidence of VT and is indicated in class 1:3 and compensated class for heart failure for which it is associated with mortality benefit metoprolol causes less drowsiness than Atenolol natol is a non-selective beta blocker which is very long acting water soluble and used to treat angina hypertension and for the prevention of ver seal bleeding it is contraindicated in patients with severe COPD or AV blockade greater than first degree the dosage should be reduced in those who have renal dysfunction and who are elderly adverse effects include dizziness cold extremities as well as insomnia and vivid dreams sool is a unique non-selective beta blocker with class 3 anti- rythmic activities it is water soluble it is used to treat life-threatening ventricular arrhythmias paroxysmal atrial fibrillation used in the maintenance of sinus rhythm in symptomatic atrial fibrillation and atrial flutter and hypertension contraindications include renal dysfunction congenital or acquired Long QT syndromes and are not to be given with non-p potassium sparing diuretics or drugs that prolong QT intervals a major adverse effect includes torad de point although rare but usually in association with hypokalemia timolol is a non- cardioselective beta blocker which is lipid soluble and six times more potent than Propranolol it is used to treat hypertension act as migraine prophylaxis and treat glaucoma it decreases cardiac mortality postm and decreases sudden cardiac death postm nebivolol is a newer beta blocker which is the most highly beta 1 selective agent tested more rigorous clinical trial data is needed though it causes nitric oxide mediated vasod dilation and is indicated for essential hypertension it can accumulate in patients with renal or hepatic dysfunction that takes us to the end of this presentation on Class 2 drugs beta [Music] blockers