Cardiac Arrhythmias Past Paper PDF

as SA node pass electrical signals to AV Node, the atrium contracts S3 and S4 beats are only present in Athletes, children, pregnant women Normal people only have S1 and S2 Sinoatrial...

as SA node pass electrical signals to AV Node, the atrium contracts S3 and S4 beats are only present in Athletes, children, pregnant women Normal people only have S1 and S2 Sinoatrial node -natural pacemaker of the heart F A AtrioventricularEnode- receive electrical signal B from SA node  Identify the parts of the heart involved in the cardiac conduction system. Write the letter that corresponds with the given structures below. F SA Node _____ A Left Bundle Branch _____ E AV Node _____ _____Interventricular septum D D AV Bundle _____ _____ Purkinje Fibers C aka Bundle of His Right Bundle branch The Electrophysiology of Normal Cardiac Rhythm The electrical impulse that triggers a normal cardiac contraction originates at regular intervals in the sinoatrial (SA) node (see next figure), usually at a frequency of 60–100 bpm. This impulse spreads rapidly through the atria and enters the atrioventricular (AV) node, which is normally the only conduction pathway between the atria and ventricles. Conduction through the AV node is slow, requiring about 0.15 seconds. (This delay provides time for atrial contraction to propel blood into the ventricles.) The impulse then propagates down the His-Purkinje system and invades all parts of the ventricles, beginning with the endocardial surface near the apex and ending with the epicardial surface at the base of the heart. Activation of the entire ventricular myocardium is complete. in less than 0.1 second. As a result, ventricular contraction is synchronous and hemodynamically effective. Arrhythmias represent electrical activity that deviates from the above description as a result of an abnormality in impulse initiation and/or impulse propagation. (Harvey & Grant, 2018) To understand how antiarrhythmic drugs work, you need to understand the electrophysiology of normal contraction of heart. Electrophysiology – Resting potential  A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell  Caused by unequal distribution of ions inside vs. outside cell  Na+ higher outside than inside cell  Ca+ much higher outside than inside cell  K+ higher inside cell than outside Chloride are also inside the cells  Maintenance by ion selective channels, active pumps and exchangers Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020 The Antiarrhythmic Drugs 1. Class I – blockers of fast Na+ channels  Subclass IA Cause moderate Phase 0 depression Prolong repolarization Increased duration of action potential Includes  Quinidine – 1st antiarrhythmic used, treat both atrial and ventricular arrhythmias, increases refractory period  Procainamide - increases refractory period but side effects  Disopyramide – extended duration of action, used only for treating ventricular arrthymias  Subclass IB Weak Phase 0 depression Shortened depolarization Decreased action potential duration Includes:  Lidocaine (also acts as local anesthetic) – blocks Na+ channels mostly in ventricular cells, also good for digitalis-associated arrhythmias  Mexiletine - oral lidocaine derivative, similar activity  Phenytoin – anticonvulsant that also works as antiarrhythmic similar to lidocaine  Subclass IC Strong Phase 0 depression No effect of depolarization No effect on action potential duration Includes:  Flecainide (initially developed as a local anesthetic)  Slows conduction in all parts of heart,  Also inhibits abnormal automaticity  Propafenone Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) MRLangit2020   Also slows conduction  Weak β – blocker  Also some Ca2+ channel blockade 2. Class II – β–adrenergic blockers  Based on two major actions 1) blockade of myocardial β–adrenergic receptors 2) Direct membrane-stabilizing effects related to Na+ channel blockade  Includes Propranolol  causes both myocardial β–adrenergic blockade and membrane-stabilizing effects  Slows SA node and ectopic pacemaking  Can block arrhythmias induced by exercise or apprehension  Other β–adrenergic blockers have similar therapeutic effect Metoprolol Nadolol Atenolol Acebutolol Pindolol Sotalol Timolol Esmolol 3. Class III – Action Potential Prolomging Agents (K+ channel blockers)  Developed because some patients negatively sensitive to Na channel blockers  Cause delay in repolarization and prolonged refractory period  Includes Amiodarone – prolongs action potential by delaying K+ efflux but many other effects characteristic of other classes Ibutilide – slows inward movement of Na+ in addition to delaying K + influx. Bretylium – first developed to treat hypertension but found to also suppress ventricular fibrillation associated with myocardial infarction Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) MRLangit2020  Dofetilide - prolongs action potential by delaying K+ efflux with no other effects 4. Class IV – Ca2+ channel blockers  slow rate of AV-conduction in patients with atrial fibrillation  Includes Verapamil – blocks Na+ channels in addition to Ca2+; also slows SA node in tachycardia Diltiazem 5, Miscellaneous Certain agents used for the treatment of arrhythmias do not fit the conventional class 1–4 organization. These include digitalis, adenosine, magnesium, and potassium. It is also becoming clear that certain nonantiarrhythmic drugs, such as drugs acting on the renin-angiotensin-aldosterone system, fish oil, and statins, can reduce recurrence of tachycardias and fibrillation in patients with coronary heart disease or congestive heart failure. See next page for learning activity.   For each of the following miscellaneous antiarrhythmic drugs, tabulate the (a) Mechanism of Action, (b) Effects, and (c) three (3) adverse effects (avoid repetition): Anti-Arrhythmic Mechanism of Action Effects Adverse Effects agents Adenosine Magnesium Potassium Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) MRLangit2020  Introduction: Drugs Used in Cardiac Arrhythmias The term "arrhythmia" refers to any change from the normal sequence of electrical impulses. The electrical impulses may happen too fast, too slowly, or erratically – causing the heart to beat too fast, too slowly, or erratically. When the heart doesn't beat properly, it can't pump blood effectively. When the heart doesn't pump blood effectively, the lungs, brain and all other organs can't work properly and may shut down or be damaged. (American Heart Association, 2016) Some arrhythmias can precipitate more serious or even lethal rhythm disturbances; for example, early premature ventricular depolarizations can precipitate ventricular fibrillation. In such patients, antiarrhythmic drugs may be lifesaving. On the other hand, the hazards of antiarrhythmic drugs—and in particular the fact that they can precipitate lethal arrhythmias in some patients—have led to a reevaluation of their relative risks and benefits. In general, treatment of asymptomatic or minimally symptomatic arrhythmias should be avoided for this reason. (Harvey & Grant, 2018) No question – the heart is a crucial organ. And arrhythmia causes the heart to beat too quickly, too slowly or erratically. Hijacking the heart’s vital rhythm and pumping function can have serious consequences. So arrhythmia matters. It is important for a future pharmacist like you to understand the risk every patient may have, to be knowledgeable with the treatment they may have, and how else a pharmacist may take care of the cardiac health of the patients. At the end of this Unit, you should be able to: 1. Review the electrophysiology of normal cardiac rhythm 2. Discuss the mechanisms of arrhythmias 3. Describe pharmacokinetic properties, mechanisms of action, clinical application, pharmacologic and toxic effects of: a. Class 1A, 1B and 1C antiarrhythmics b. Class 2 antiarrhythmics c. Class 3 antiarrhythmics d. Class 4 antiarrhythmics e. Miscellaneous Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020 as SA node pass electrical signals to AV Node, the atrium contracts S3 and S4 beats are only present in Athletes, children, pregnant women Normal people only have S1 and S2 Sinoatrial node -natural pacemaker of the heart F A AtrioventricularEnode- receive electrical signal B from SA node  Identify the parts of the heart involved in the cardiac conduction system. Write the letter that corresponds with the given structures below. F SA Node _____ A Left Bundle Branch _____ E AV Node _____ _____Interventricular septum D D AV Bundle _____ _____ Purkinje Fibers C aka Bundle of His Right Bundle branch The Electrophysiology of Normal Cardiac Rhythm The electrical impulse that triggers a normal cardiac contraction originates at regular intervals in the sinoatrial (SA) node (see next figure), usually at a frequency of 60–100 bpm. This impulse spreads rapidly through the atria and enters the atrioventricular (AV) node, which is normally the only conduction pathway between the atria and ventricles. Conduction through the AV node is slow, requiring about 0.15 seconds. (This delay provides time for atrial contraction to propel blood into the ventricles.) The impulse then propagates down the His-Purkinje system and invades all parts of the ventricles, beginning with the endocardial surface near the apex and ending with the epicardial surface at the base of the heart. Activation of the entire ventricular myocardium is complete. in less than 0.1 second. As a result, ventricular contraction is synchronous and hemodynamically effective. Arrhythmias represent electrical activity that deviates from the above description as a result of an abnormality in impulse initiation and/or impulse propagation. (Harvey & Grant, 2018) To understand how antiarrhythmic drugs work, you need to understand the electrophysiology of normal contraction of heart. Electrophysiology – Resting potential  A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell  Caused by unequal distribution of ions inside vs. outside cell  Na+ higher outside than inside cell  Ca+ much higher outside than inside cell  K+ higher inside cell than outside Chloride are also inside the cells  Maintenance by ion selective channels, active pumps and exchangers Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020 Cardiac Action Potential  Divided into five phases (0,1,2,3,4)  Phase 4 - resting phase (resting membrane potential) cardiac cells are waiting for the impulse to pass Phase cardiac cells remain in until stimulated Associated with diastole portion of heart cycle  Addition of current into cardiac muscle (stimulation) causes  Phase 0 – opening of fast Na channels and rapid depolarization Na will enter the cell, K and Cl will exit Drives Na+ into cell (inward current), changing membrane potential Transient outward current due to movement of Cl- and K+  Phase 1 – initial rapid repolarization closing of the Na Channel Closure of the fast Na+ channels Phase 0 and 1 together correspond to the R and S waves of the ECG  Phase 2 - plateau phase Calcium is still going inside, longest Potassium still going out sustained by the balance between the inward movement of Ca+ and outward movement of K+ Has a long duration compared to other nerve and muscle tissue Normally blocks any premature stimulator signals (other muscle tissue can accept additional stimulation and increase contractility in a summation effect) Corresponds to ST segment of the ECG.  Phase 3 – repolarization Potassium will now be completely outside due to continuous efflux, K channels closes and repolarization hapens K+ channels remain open, Allows K+ to build up outside the cell, causing the cell to repolarize K + channels finally close when membrane potential reaches certain level Corresponds to T wave on the ECG Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  QRS complex D E R wave The figure on the left is an ECG showing the wave segments. ST segment PR segment T wave P wave  Identify the parts as labelled. Write the I J B letters of the label that corresponds to the A given wave segments. A P wave ____ C PR interval ____ Q wave F Q wave ____ B PR segment ____ C F ____ E R wave ____ D QRS complex PR interval G S wave H ____ G S wave ____ I ST segment QT interval J T wave ____ ____ H QT interval An electrocardiogram — abbreviated as EKG or ECG — is a painless, non-invasive procedure that records the heart’s electrical activity and can help diagnose arrhythmias. With each beat, an electrical impulse (or “wave”) travels through the heart. This wave causes the muscle to squeeze and pump blood from the heart. A normal heartbeat on ECG will show the timing of the top and lower chambers. The right and left atria or upper chambers make the first wave called a “P wave" — following a flat line when the electrical impulse goes to the bottom chambers. The right and left bottom chambers or ventricles make the next wave called a “QRS complex." The final wave or “T wave” represents electrical recovery or return to a resting state for the ventricles. Purposes of ECG An ECG gives two major kinds of information. First, by measuring time intervals on the ECG, a doctor can determine how long the electrical wave takes to pass through the heart. Finding out how long a wave takes to travel from one part of the heart to the next shows if the electrical activity is normal or slow, fast or irregular. Second, by measuring the amount of electrical activity passing through the heart muscle, a cardiologist may be able to find out if parts of the heart are too large or are overworked. (American Heart Association, 2015) Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  Arrhythmias: The Abnormal Heart Rhythms Arrhythmias are abnormal beats. The term "arrhythmia" refers to any change from the normal sequence of electrical impulses, causing abnormal heart rhythms. Arrhythmias may be completely harmless or life- threatening. Some arrhythmias are so brief (for example, a temporary pause or premature beat) that the overall heart rate or rhythm isn't greatly affected. But if arrhythmias last longer, they may cause the heart rate to be too slow or too fast or the heart rhythm to be erratic – so the heart pumps less effectively. (American Heart Association, 2016)  Matching Type. Match the items in column A, the types of Arrhythmia, to the items in Column B, the definitions. Column A Column B F Atrial Fibrillation _____ A. early heart beat aka “atrial flutter” E Bradycardia _____ B. heart does not beat normally B Conduction Disorders _____ C. very fast heart rate A Premature contraction _____ D. disorganized contraction of the lower chambers of the heart _____ C Tachycardia E. slow heart rate D Ventricular Fibrillation _____ F. upper heart chambers contract irregularly Mechanism of Arrhythmias Many factors can precipitate or exacerbate arrhythmias: ischemia, hypoxia, acidosis or alkalosis, electrolyte abnormalities, excessive catecholamine exposure, autonomic influences, drug toxicity (eg, digitalis or antiarrhythmic drugs), overstretching of cardiac fibers, and the presence of scarred or otherwise diseased tissue. However, all arrhythmias result from (1) disturbances in impulse formation and/or (2) disturbances in impulse conduction. (Harvey & Grant, 2018) other parts initiate the conduction may be because of blockade ex: LBBB aside from SA node Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation. Thus, the aim of therapy of the arrhythmias is to reduce ectopic pacemaker activity and modify conduction or refractoriness in reentry circuits to disable circus movement. The most widely used scheme for the classification of antiarrhythmic drug actions recognizes four classes: APD= Action Potential duration 1. Class 1 action is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade. Drugs with class 1A action prolong the APD and dissociate from the channel with intermediate kinetics; drugs with class 1B action shorten the APD in some tissues of the heart and dissociate from the channel with rapid kinetics; and drugs with class 1C action have minimal effects on the APD and dissociate from the channel with slow kinetics. B-blocker 2. Class 2 action is sympatholytic. Drugs with this action reduce β-adrenergic activity in the heart. blocker Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  Potassium channel blocker 3. Class 3 action manifests as prolongation of the APD or effective refractory period. Most drugs with this action block the rapid component of the delayed rectifier potassium current, IKr. 4. Class 4 action is blockade of the cardiac calcium current. This action slows conduction in regions where the action potential upstroke is calcium dependent, eg, the SA and AV nodes (Harvey & Grant, 2018)  For full description of the pharmacokinetic properties, mechanisms of action, clinical applications, pharmacologic and toxic effects of the antiarrhythmic drugs as mentioned in the preceding paragraph, kindly read Chapter 14 of your textbook Basic and Clinical Pharmacology, Fourteenth Edition (Ed. Bertram Katzung), pages 236-252. The Summary of Anti-Arrhythmic Drugs tabulated in pages 250-251 would be very helpful in your study. Do review the Power Point Presentation Filename: Antiarrhythmics_MRL.pdf. This contains discussions on the different drugs for anti-arrhythmia, and other information about cardiac arrhythmia. Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  Drugs for Heart Failure Mark Ryan G. Langit, RPh, MSPharm Professor Department of Pharmacy Saint Louis University First Term, AY 2020-2021 HEART FAILURE - medical condition characterized by impairment of left ventricle - there is no ability to pump sufficient oxygenated blood - inadequate supply of oxygenated blood coming from ventricle  can result to hospitalization Symptoms of heart failure based on exertion Class1 - asymptomatic - no limitation on physical activity Class 2 - mild to moderate moderation on - physical activity - can be relieved during at rest Class 3 - marked limitation on physical activity - can happen even during at rest Class 4 - any physical activity can trigger heart failure symptoms 2 Forms of heart failure 1. Low output - most common  no metabolic demand/requirement, but the heart cannot compensate with the requirements for oxygenated blood 2. High output - characterized by metabolic disorder Ex. Hyperthyroidism - increases demand for oxygenated blood because patient suffers from palpitation or tachycardia. Anemia - hematopoietic disorder characterized by low levels of haemoglobin (oxygenated blood)  2 major classes of heart failure 1. Left sided heart failure - blood accumulates within the left ventricle 2. Right sided heart failure - blood accumulates in the right ventricle. 1. Inotropic agent (increases the force of contraction) * cardiac glycoside - digitalis - Most important ion affected by digitalis isK channel, therefore it can cause hypokalemia - Alternative for hypokalemia is KCl or MgSO4 Deslanoside - alternative for rapid digitalization Digitoxin - former drug of choice for heart failure - obsolete - bec. Lipid soluble, has long duration of action there is high risk of reabsorption Digoxin - replace the digitoxin - water soluble with shortest duration of action - provide rapid and onset duration of action - has narrow therapeutic index Therapeutic conc.: 0.5-1.5 mg/ml More than 1.5 mg/ml patient can experience toxicity Antidote: Digibind/digitalis fab fragment 2. Diuretics -to reduce fluid overload in patient suffering from fluid retention *Thiazide / loop diuretics - commonly used - same cardiac effect with cardiac glycosides (hypokalemia- can cause digitalis toxicity, must be given separately with cardiac glycosides) 3. Vasodilator - main goal is to reduce pulmonary congestion Use: left sided heart failure - it can increase cardiac output Ex. Organic nitrates, sodium nitroprusside Ex. Minoxidil, hydralazine, prazosin  Angiotensin Converting Enzyme Inhibitor - first line agent for heart failure - beneficial to prevent cardiac hypertrophy Captopril - most widely used Ramipril, quinapril can also be used except enalapril Enalapril - only use for hypertensive emergency Prob with vasodilator such as ACEI can promote fluid retention therefore must be given with beta blocker or diuretics Beta blockers - prophylaxis for px with chronic heart failure Carvedilol - first beta blocker approved for heart failure - mixed acting alpha and beta blocker Cardioselective : bisoprolol and metoprolol Other inotropic agents - only applicable to patient refractory to digitalis therapy Ex. Dopamine - agonist of dopamine 1 receptor - has renal effect, however can cause tachycardia (can increase BP) Dobutamine - chemically related structure of dopamine - beta 1 agonist - has no renal effect - can cause tachycardia or palpitation  Other inotropic agents Bipyridines -last resort in case of dopamine and dobutamine resistance - inhibitor of the enzyme phosphodiesterase isoform 5 (PDE5) -increases level of CAMP responsible for inotropic activity Ex. Inamrinone and milrinone -both orally active drug but given intravenously Other inotropic agents Inamrinone - also known in the market as amrinone - toxic effect : hepatotoxic & aplastic anemia - can cause bone marrow suppression and liver damage Milrinone - associated with thrombocytopenia - can cause haemorrhage or bleeding  Drugs for Cardiac Arrhythmia Mark Ryan G. Langit, RPh, MSPharm Professor Department of Pharmacy Saint Louis University First Term, AY 2020-2021  Arrhythmia Defined as the abnormal firing rate, regularity or site of origin of cardiac impulse, involve irregular and abnormal heart rhythm.  Normal heart rhythm: 60-90 beats per minute  * heart rhythm is regulated by the SA Node (phase maker of heart)  2 Division under ECG PR interval - takes place in atria QT interval - takes place in the ventricle. P wave - represents atrial depolarization (contracts-atria, relax-ventricle) PR interval - duration of atrial repolarization QRS interval - ventricular depolarization QT interval - duration of ventricular repolarization T wave - ventricular repolarization Arrhythmia is common under QT interval because it is the site of ventricular contraction ACTION POTENTIAL ANTI-ARRHYTHMIC DRUGS A. Type I anti-arrhythmic drugs B. Type II anti-arrhythmic drugs C. Type III anti-arrhythmic drugs D. Type IV anti-arrhythmic drugs Class 1 - Na channel blocker - suppresses phase 0  Class 1A - fast Na channel blocker  Suppress phase 0, resulting to prolongation of action potential Drugs: *Quinidine - d-isomer of anti-malarial drug quinine - has moderate anti cholinergic effect toxic effect: cinchonism Characterized by tinnitus, decreased hearing, vertigo and headache  *Procainamide - with ganglionic blocking effect  - prodrug, active form is NAPA (N-acetyl procainamide)  -has weakest anti cholinergic effect  -ADR: allergic reaction (SLE like syndrome), hypotension because of ganglionic blocking effect.  *Disopyramide - With greatest/strongest anticholinergic effect (ADR: atropine like toxicity)  Atropine causes dry mouth, urinary retention, blurring of vision, constipation. Class 1B - shortens the action of action potential  shortens effective refractory period * lidocaine - local anesthetic with membrane stabilizing activity - least cardiotoxic drug in class 1B - use: DOC: digitalis induced arrhythmia DOC: Sustain ventricular arrhythmia in patient with heart attack 2nd line: procainamide  neutotoxic effect: tremor, paresthesia, light headedness *mexilitine -orally active congener of lidocaine *Procainide -congener of mexilitine -obsolete can cause pulmonary fibrosis *phenytoin - antiseizure drug indicated as 2nd line agent for digitalis induces arrhythmia -associated with hirsutism and gingival hyperplasia  Class 1C *flecainide - potent Na and K channel inhibitor - no anti-muscarinic effect but cause life threatening ventricular tachycardia *propafenone -chemically related drug to propranolol -has weak beta blocking activity *Moricizine -derivative of antihistamine phenothiazine -obsolete anti-arrhythmic together with Encainide(chemically related to flecainide) Class 2 - beta blockers  -reduces phase 4 action potential  -can reduce heart rate and force of contraction   -propranolol most widely used, however causes bronchospasm and heart block  -metoprolol or esmolol: preferred Class 3 - K channel blocker - prolong phase 3 action potential * bretylium - with similar MOA with guanethidine - inhibits the release of norepinephrine in synaptic cleft Use: life threatening ventricular tachycardia ADR: Hypotension *amiodarone - contains highest elemental content of iodine - has vasodilating effect causing flushing - toxic effect: pulmonary fibrosis - has endocrine effect  can cause iodide induced hyperthyroidism - dronedarone - alternative if you have hyperthyroidiasm -blocks iodine atom on its structure *sotalol -with beta blocking effect -with ventricular tachycardia -associated with constipation and metallic taste Class 4 - Ca channel blocker - prolong phase 2 action potential *verapamil and diltiazem - most widely used -nifedipine cannot be given because it is a cardiac stimulant Miscellaneous anti-arrhythmic *digitalis -for heart failure, increases the rate of contraction  increases force of contraction -can suppress Na K Mg ion (K ion is the most critical because hypokalemia can increase digoxin absorption) Digibind/digitalis fab fragments-antidote KCl& MgSO4 - adjunct drug Cardiac Action Potential  Divided into five phases (0,1,2,3,4)  Phase 4 - resting phase (resting membrane potential) cardiac cells are waiting for the impulse to pass Phase cardiac cells remain in until stimulated Associated with diastole portion of heart cycle  Addition of current into cardiac muscle (stimulation) causes  Phase 0 – opening of fast Na channels and rapid depolarization Na will enter the cell, K and Cl will exit Drives Na+ into cell (inward current), changing membrane potential Transient outward current due to movement of Cl- and K+  Phase 1 – initial rapid repolarization closing of the Na Channel Closure of the fast Na+ channels Phase 0 and 1 together correspond to the R and S waves of the ECG  Phase 2 - plateau phase Calcium is still going inside, longest Potassium still going out sustained by the balance between the inward movement of Ca+ and outward movement of K+ Has a long duration compared to other nerve and muscle tissue Normally blocks any premature stimulator signals (other muscle tissue can accept additional stimulation and increase contractility in a summation effect) Corresponds to ST segment of the ECG.  Phase 3 – repolarization Potassium will now be completely outside due to continuous efflux, K channels closes and repolarization hapens K+ channels remain open, Allows K+ to build up outside the cell, causing the cell to repolarize K + channels finally close when membrane potential reaches certain level Corresponds to T wave on the ECG Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  QRS complex D E R wave The figure on the left is an ECG showing the wave segments. ST segment PR segment T wave P wave  Identify the parts as labelled. Write the I J B letters of the label that corresponds to the A given wave segments. A P wave ____ C PR interval ____ Q wave F Q wave ____ B PR segment ____ C F ____ E R wave ____ D QRS complex PR interval G S wave H ____ G S wave ____ I ST segment QT interval J T wave ____ ____ H QT interval An electrocardiogram — abbreviated as EKG or ECG — is a painless, non-invasive procedure that records the heart’s electrical activity and can help diagnose arrhythmias. With each beat, an electrical impulse (or “wave”) travels through the heart. This wave causes the muscle to squeeze and pump blood from the heart. A normal heartbeat on ECG will show the timing of the top and lower chambers. The right and left atria or upper chambers make the first wave called a “P wave" — following a flat line when the electrical impulse goes to the bottom chambers. The right and left bottom chambers or ventricles make the next wave called a “QRS complex." The final wave or “T wave” represents electrical recovery or return to a resting state for the ventricles. Purposes of ECG An ECG gives two major kinds of information. First, by measuring time intervals on the ECG, a doctor can determine how long the electrical wave takes to pass through the heart. Finding out how long a wave takes to travel from one part of the heart to the next shows if the electrical activity is normal or slow, fast or irregular. Second, by measuring the amount of electrical activity passing through the heart muscle, a cardiologist may be able to find out if parts of the heart are too large or are overworked. (American Heart Association, 2015) Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  Arrhythmias: The Abnormal Heart Rhythms Arrhythmias are abnormal beats. The term "arrhythmia" refers to any change from the normal sequence of electrical impulses, causing abnormal heart rhythms. Arrhythmias may be completely harmless or life- threatening. Some arrhythmias are so brief (for example, a temporary pause or premature beat) that the overall heart rate or rhythm isn't greatly affected. But if arrhythmias last longer, they may cause the heart rate to be too slow or too fast or the heart rhythm to be erratic – so the heart pumps less effectively. (American Heart Association, 2016)  Matching Type. Match the items in column A, the types of Arrhythmia, to the items in Column B, the definitions. Column A Column B F Atrial Fibrillation _____ A. early heart beat aka “atrial flutter” E Bradycardia _____ B. heart does not beat normally B Conduction Disorders _____ C. very fast heart rate A Premature contraction _____ D. disorganized contraction of the lower chambers of the heart _____ C Tachycardia E. slow heart rate D Ventricular Fibrillation _____ F. upper heart chambers contract irregularly Mechanism of Arrhythmias Many factors can precipitate or exacerbate arrhythmias: ischemia, hypoxia, acidosis or alkalosis, electrolyte abnormalities, excessive catecholamine exposure, autonomic influences, drug toxicity (eg, digitalis or antiarrhythmic drugs), overstretching of cardiac fibers, and the presence of scarred or otherwise diseased tissue. However, all arrhythmias result from (1) disturbances in impulse formation and/or (2) disturbances in impulse conduction. (Harvey & Grant, 2018) other parts initiate the conduction may be because of blockade ex: LBBB aside from SA node Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation. Thus, the aim of therapy of the arrhythmias is to reduce ectopic pacemaker activity and modify conduction or refractoriness in reentry circuits to disable circus movement. The most widely used scheme for the classification of antiarrhythmic drug actions recognizes four classes: APD= Action Potential duration 1. Class 1 action is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade. Drugs with class 1A action prolong the APD and dissociate from the channel with intermediate kinetics; drugs with class 1B action shorten the APD in some tissues of the heart and dissociate from the channel with rapid kinetics; and drugs with class 1C action have minimal effects on the APD and dissociate from the channel with slow kinetics. B-blocker 2. Class 2 action is sympatholytic. Drugs with this action reduce β-adrenergic activity in the heart. blocker Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020  Potassium channel blocker 3. Class 3 action manifests as prolongation of the APD or effective refractory period. Most drugs with this action block the rapid component of the delayed rectifier potassium current, IKr. 4. Class 4 action is blockade of the cardiac calcium current. This action slows conduction in regions where the action potential upstroke is calcium dependent, eg, the SA and AV nodes (Harvey & Grant, 2018)  For full description of the pharmacokinetic properties, mechanisms of action, clinical applications, pharmacologic and toxic effects of the antiarrhythmic drugs as mentioned in the preceding paragraph, kindly read Chapter 14 of your textbook Basic and Clinical Pharmacology, Fourteenth Edition (Ed. Bertram Katzung), pages 236-252. The Summary of Anti-Arrhythmic Drugs tabulated in pages 250-251 would be very helpful in your study. Do review the Power Point Presentation Filename: Antiarrhythmics_MRL.pdf. This contains discussions on the different drugs for anti-arrhythmia, and other information about cardiac arrhythmia. Unit 4: Drugs Used in Cardiac Arrhythmias Pharm 315 (Pharmacology 2) Unit Introduction MRLangit2020