3arrythmia pharmacotherapy


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3arrythmia pharmacotherapy

  1. 1. Cardiac arrhythmia • Abnormal cardiac rhythm usually involving a change in rate or regularity. • Synonym: dysrhythmia
  2. 2. Etiology Physiological: -sympathetic or parasympathetic control changes eg. Stress , anxiety, exercise , smoking. Hypothyroidism, Hyperthyroidism Hypoadrenalism Hyperkalemia hypokalemia and other electrolyte changes.
  3. 3. Pathological: Valvular heart disease. Ischemic heart disease.----------MI causing death of pacemaker cells or conducting tissue. Hypertensive heart diseases. Congenital heart disease. Cardiomyopathies. Carditis. RV dysplasia. Drug related. Pericarditis. Pulmonary diseases. Others.
  4. 4. CLINICAL EVALUATION I. PHYSICAL FINDINGS Palpitation. Dizziness. Chest Pain. Abnormal pulse rate , rhythm or amplitude Dyspnea. Anxiety and confusion (from reduced brain perfusion) Fainting (syncope) Skin pallor or cyanosis Reduced blood pressure Weakness Convulsions Decreased urinary output Sudden cardiac death.
  5. 5. II. DIAGNOSTIC TEST RESULTS ECG electrophysiological (EP) testing His bundle study III. LAB FINDINGS: hyperkalemia (>5mEq/L) Hypocalcemia (<4.5mEq/L) hypomagnesemia(<2.5mEq/L)
  6. 6. Mechanism of Arrhythmogensis 1. Disorder of impulse formation. a) Automaticity. b) Triggered Activity. 1) Early after depolarization. 2) Delayed after depolarization. 2. Disorder of impulse conduction. a) b) Block – Reentry. Reflection. 3. Combined disorder.
  7. 7. Nomenclature for describing arrhythmias • Rate tachycardia bradycardia • Origin: sinus atrial nodal supraventricular re-entrant ventricular
  8. 8. • Pattern: ectopic Premature contraction paroxysmal flutter fibrillation block torsades electromechanical dissociation
  9. 9. Duration: i) paroxysmal- self terminating episodes upto 7 days ii) persistent -non self terminating more than 7 days iii) permanent - not responding to cardioversion attempts iv) recurrent: returning after once stopped.
  10. 10. Electrophysiological treatment 1) Cardioversion 2) Implantable Cardiac Defibrillator (ICD) 3) Pace maker 4) Lead extraction
  11. 11. Pharmacology of anti- arrhythmic drugs
  12. 12. Quinidine (Class IA prototype) • Other examples: Procainamide, Disopyrimide General properties: a. D-isomer of quinine b. As with most of the Class I agents - moderate block of sodium channels - decreases automaticity of pacemaker cells - increases effective refractory period/AP duration
  13. 13. Actions of quinidine • Cardiac effects a. ↓ automaticity, conduction velocity and excitability of cardiac cells. b. Preferentially blocks open Na channels c. Recovery from block slow in depolarized tissue; lengthens refractory period (RP) d. All effects are potentiated in depolarized tissues e. Increases action potential duration (APD) and prolongs AP repolarization via block of K channels; decreases reentry f. Indirect action: anticholinergic effect (accelerates heart), which can speed A-V conduction.
  14. 14. – Cardiac tissue: • • • • • Reduce automaticity Reduce excitability Reduce conductivity Prolong refractory period Reflex tachycardia – Other action: • Anti-malarial • Anti-pyretic • Decrease B.P (vasodilation)
  15. 15. Pharmacokinetics: – Orally active; i.v. in emergency; i.m. painful – 80% bound to plasma proteins – Half-life: 4-6 hrs – Metabolized by liver (75%) – Excretion: unchanged fraction by kidney
  16. 16. Extracardiac a. Blocks alpha-adrenoreceptors to yield vasodilatation. b. Other strong antimuscarinic actions Toxicity - "Quinidine syncope"(fainting)- due to disorganized ventricular tachycardia - associated with greatly lengthened Q-T interval; can lead to Torsades de Pointes (VT, precursor to ventricular fibrillation) - negative inotropic action (decreases contractility) - GI - diarrhea, nausea, vomiting - CNS effects - headaches, dizziness, tinnitus (quinidine “Cinchonism”)
  17. 17. • Adverse effects: – – – – – – – – – – Heart block Sinus arrest Myocardial depression Q-T prolongation Ventricular fibrillation Nausea Vomiting Diarrhoea Rash Oedema
  18. 18. Indications : 1) Premature atrial contractions 2) Paroxysmal atrial fibrillation and flutter 3) Intra-atrial and A-V nodal reentrant dysrhythmias 4) Wolff-Parkinson-White tachycardias (SVT, A-V bypass) 5) Premature ventricular contractions (PVCs) 6) Useful in treating chronic dysrhythmias requiring outpatient treatment • Also as anti-malarial • Anti-pyretic • During digitalis therapy
  19. 19. • Contraindications: – Quinidine intolerance – Digitalis intoxication – Heart failure – Hypotension – hypokalemia
  20. 20. Procainamide (Class 1A) also Disopyrimide Cardiac effects a) Similar to quinidine, less muscarinic & alphaadrenergic blockade b) Also has negative inotropic action . Extracardiac effects a) Ganglionic blocking reduces peripheral vascular resistance Toxicity a) Cardiac: Similar to quinidine; cardiac depression b) Noncardiac: Syndrome resembling lupus erythematosus
  21. 21. Pharmacokinetics/therapeutics a. Administered orally, i-v b. Major metabolite in liver is N-acetylprocainamide (NAPA), a weak Na channel blocker with class III activity. Bimodal distribution in population of rapid acetylators, who can accumulate high levels of NAPA. c. T1/2 = 3-4 hours; necessitates frequent dosing; kidney chief elimination path. NAPA has longer T1/2 and can accumulate d. Usually used short-term. Commonly used in CCUs for ventricular dysrhythmias associated with acute myocardial infarctions (MI)
  22. 22. Lidocaine (Class IB prototype) Other examples: Mexiletine, Phenytoin, Tocainide General a). Commonly used antidysrhythmic agent in emergency care (decreasing use) b) Given i-v; widely used in ICU-critical care units c)Low toxicity (especially cardiac, good therapeutic index) d) A local anesthetic, works on nerve at higher doses
  23. 23. • Mechanism of anti-arrhythmic effect of lignocaine: – It has membrane stabilizing effect by blocking both activated and inactivated sodium channels; which in turn supresses SA node and also ectopic beats. – Shortens refractory period and action potential; make uniform rhythm
  24. 24. Cardiac effects a. Generally decreases APD, hastens AP repolarization, decreases automaticity and increases refractory period in depolarized cells. b. Exclusively acts on Na channels in depolarized tissue by blocking open and inactivated (mainly) Na channels c. Potent suppresser of abnormal activity d. Most Na channels of normal cells rapidly unblock from lidocaine during diastole; few electrophysiological effects in normal tissue Toxicity: - least cardiotoxic, high dose can lead to hypotension • - tremors, nausea, slurred speech, convulsions – Bradycardia, Hypotension, Dizziness, Blurred vision, Sleepiness, Confusion
  25. 25. • Pharmacokinetics a. i-v, since extensive first pass hepatic metabolism b. T1/2 = 0.5-4 hours Indications a) Effective in suppressing dysrhythmia associated with depolarised.( Tissue ischemia; digitalis toxicity); ineffective against dysrhythmias in normal tissue (atrial flutter). b) Suppresses ventricular tachycardia; prevents fibrillation after acute MI; rarely used in supraventricular dysrhythmias
  26. 26. Contraindications of lidocaine • Heart block, second or third degree (without pacemaker) • Severe sinoatrial block (without pacemaker) • Serious adverse drug reaction to lidocaine or amide local anaesthetics • Concurrent treatment with quinidine, flecainide, disopyramide, procainamide (Class I antiarrhythmic agents) • Prior use of Amiodarone hydrochloride • Hypotension not due to Arrhythmia • Bradycardia • Accelerated idioventricular rhythm • Pacemaker • Porphyria, especially acute porphyria (AIP)
  27. 27. Phenytoin 1. Non-sedative anticonvulsant used in treating epilepsy ('Dilantin') 2. Limited efficacy as antidysrhythmic (second line antiarrythmic) 3. Suppresses ectopic activation by blocking Na and Ca channels 4. Especially effective against digitalis-induced dysrhythmias 5. T1/2 = 24 hr – metabolized in liver 6. Gingival hyperplasia (40%)
  28. 28. Flecainide (Class IC prototype) Other examples: Lorcainide, Propafenone, Indecainide, Moricizine Depress rate of rise of AP without change in refractoriness or APD 1. Decreases automaticity, conduction in depolarized cells. 2. Marked block of open Na channels (decreases Ph. 0); no change repolarization. 3. Used primarily for ventricular dysrhythmias but effective for atrial too 4. No antimuscarinic action 5. Suppresses premature ventricular contractions (PVCs) 6. Associated with significant mortality; thus, use limited to last resort applications like treating ventricular tachycardias 7. Significant negative inotropic effect
  29. 29. Propranolol (Class II, betaadrenoreceptor blockers) • Other agents: Metoprolol, Esmolol (short acting), Sotalol (also Class III), Acebutolol • Propranolol as anti-arrhythmic drug: – It blocks β-receptors in heart, thereby exerts • • • • Negative inotropic effect Negative chronotropic effect Depress atrioventricular conduction Depresses automaticity – It has: • Anti-arrhythmic effect • Anti-hypertensive effect • Anti-anginal-effect in CVS. a. Slow A-V conduction b. Prolong A-V refractory period
  30. 30. Cardiac effects (of propranolol), a non-selective beta blocker a. Main mechanism of action is blockade of beta receptors; ↓ Ph 4 slope which decreases automaticity under certain conditions b. Some direct local anesthetic effect by block of Na channels (membrane stabilization) at higher doses c. Increases refractory period in depolarized tissues d. Increases A-V nodal refractory period Non-cardiac: Hypotension
  31. 31. • Therapeutics a. Blocks abnormal pacemakers in cells receiving excess catecholamines (e.g. pheochromocytoma) or up-regulated beta-receptors (ie. hyperthyroidism) b. Blocks A-V nodal reentrant tachycardias; inhibits ectopic foci c. Beta-blockers are used to treat supraventricular tachydysrhythmias d. Propranolol contraindicated in ventricular failure; can lead to A-V block.
  32. 32. Amiodarone (Class III) • others: Ibutilide, Bretylium, Sotalol, Dofetilide • Dronedarone • General a. New DOC for ventricular dysrhythmias (Lidocaine, old DOC) b. prolongs refractory period by blocking potassium channels c. also member of Classes IA,II,III,IV since blocks Na, K, Ca channels and alpha and beta adrenergic receptors d. serious side effects (cardiac depression, pulmonary fibrosis, thyroid) e. effective against atrial, A-V and ventricular dysrhythmias f. widely used, very long acting (>25 d)
  33. 33. Effects of amiodarone Cardiac effects a. Block Na channels (1A), but low affinity for open channels; mainly blocks inactivated Na channels b. Block is most pronounced in tissues with long action potentials c. Weak Ca channel blocker also (Class IV activity) d. A powerful inhibitor of abnormal automaticity, decreases conduction, increases refractory period and APD. e. Has antianginal effects (blocks alpha/beta receptors and Ca channels) Extracardiac effects: Vasodilation via block of Ca channels and alpha receptors
  34. 34. • B. Non-cardiac: • i. Deposits into almost every organ • ii. Reduces clearance of drugs like procainamide, flecainide, digitalis, • quinidine and diltiazem. • iii. Thyroid dysfunction (hypo or hyperthyroidism) • iv. Pulmonary fibrosis is most serious adverse effect • v. Paresthesias (tingling, pricking, or numbness) • vi. Photosensitivity • vii. Corneal microdeposits and blurred vision • viii. Ataxia, dizziness, tremor • ix. Anorexia, nausea
  35. 35. Adverse effects of amiodarone • A. Cardiac • i. Sinus bradycardia, increase QT interval ↑risk TdP • ii. Negative inotropic action due to block of Ca channels and beta • receptors; but can improve heart failure via vasodilation. • iii. A-V block, paradoxical VTs.
  36. 36. Verapamil (Class IV, Ca++ channel blockers) • Other example: Diltiazem - CCBs increasing use and importance a. Blocks active and inactivated Ca channels, prevents Ca entry b. More effective on depolarized tissue, tissue firing frequently or areas where activity dependent on Ca channels (SA node; A-V node) c. Increases A-V conduction time and refractory period; directly slows SA and A-V node automaticity d. suppresses oscillatory depolarizing after depolarizations due to digitalis e. Dihydropyridine CCBs are generally poor antiarrythmics
  37. 37. Ca++ Channel Blockers - Actions Extracardiac a. Peripheral vasodilatation via effect on smooth muscle b. Used as antianginal / antihypertensive c. Hypotension may increase HR reflexively Toxicity a. Cardiac - Too negative inotropic for damaged heart, depresses contractility - Can produce complete A-V block b. Extracardiac - Hypotension - Constipation
  38. 38. Other antiarrythmics A. Adenosine: i.v. (15 secs), activates P1 purinergic receptors (A1) coupled to K channels, ↓CV, ↑refractory period. SVT. Flushing, hypotension, burning sensation B. Potassium ions (K+): Depress ectopic pacemakers - can depress CV → reentrant dysrhythmia C. Digoxin: used to treat atrial flutter and fibrillation - AV node ↓conduction (vagal stimulation) - myocardium ↓refractory period - Purkinje fibers ↑refractory period, ↓conduction D. Magnesium: used to treat Torsades de Pointes E. Autonomic agents: used to treat A-V block - β-agonists , anticholinergics (ie. atropine) Anticoagulant therapy: - prevent formation of systemic emboli & stroke
  39. 39. Life style changes • • • • • Eat heart-healthy foods. Increase your physical activity. Quit smoking. Cut back on caffeine and alcohol. Find ways to reduce the amount of stress in your life. • Avoid stimulant medications, such as medications found in over-the-counter treatments for colds and nasal congestion.
  40. 40. Arrythmia detected yes Is it life threatening? emergency resuscitation no is it affecting cardiac output Or threatening to do so yes Or unpleasant for the patient ? monitor , check electrolytes and possible causes. yes yes is the rate slow? Consider electrolyte pacing no correct elctrolyte abnormalities choose a drug according to origin Of arrhythmia Algorithm for treatment of arrhythmia
  41. 41. Condition Drug Sinus tachycardia Class II, IV Atrial fibrillation/flutter Class IA, IC, II, III, IV digitalis adenosine Paroxysmal supraventricular tachycardia Class IA, IC, II, III, IV adenosine AV block Atropine Ventricular tachycardia Class I, II, III Premature ventricular complexes Class II, IV Mg++ salts Digitalis toxicity Class IB Mg++ salts; KCl
  42. 42. Diagnosis Treatment Avoid Atrial Fibrillation in Patient with WPW Syndrome Direct Cardioversion+Lidocaine or Procainamide Or Ibutilide Digoxin Amiodarone Verapamil WPW and Pseudo-Inferior MI Betablocker CCB Quinidine Flecainide Pace-maker Digoxin Verapamil Atrial Flutter with 2:1 Av Conduction Digoxin 0.25 Esmolol 0.5 Mg/Kg Amiodarone 150mg Quinidine Ventricular tachycardia Magnesium-Sulphate Procainamide Amiodarone Lidocaine If failed: Cardioversion Verapamil Adenosine Atrial flutter Digoxin 0.25 Esmolol 0.5 Mg/Kg Amiodarone 150mg Quinidine
  43. 43. Drug choice in treating chronic or persistent atrial fibrillation Associated factors First choice Second choice Avoid Acute systemic illness Nothing or II IV, II I II Disopyramide Sotalol/Amiodar one Sotalol, IC Sotalo, IC Digoxin II IC Digoxin, IV IA, III Paroxysmal exercise induced vagal origin elderly Sustained AF ventricular rate control cardioversion Respiratory disorders II, IV, Digoxin II, sotalol IHD Sotalol Amiodarone I Heart failure Amiodarone Digoxin I Hypertension Sotalol Amiodarone
  44. 44. Drug classes in chronic tachyarrythmias SA node Commonly used Also used Atria AV node Accessory Ventricles pathway II II IV IV for urgent cardioversion II IC II III Digoxin III IC IA Digoxin IC II IA I
  45. 45. Common therapeutic problems in the management of arryhthmias Problem Management Narrow therapeutic range of digoxin Encourage compliance and perform TDM Beta blockers contraindicated in bronchial and peripheral vascular diseases Consider verapamil or diltiazem Verapamil induced constipation Give regular laxatives Pro-arrythmic actions of antiarrhytmics Minimise requirements of drugs , else switch to pacemaker or elctrical therapy Amiodarone sun burn Stay indoors , use sunblock