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  • Editd anti arrhythmic

    1. 1. ANTI-ARRHYTHMIC DRUGS Ma. Janetth B. Serrano, M.D.,DPBA
    2. 2. <ul><li>Cardiac Arrhythmias: </li></ul><ul><ul><li>25% treated with digitalis </li></ul></ul><ul><ul><li>50% anesthetized patients </li></ul></ul><ul><ul><li>80% patients with AMI </li></ul></ul><ul><li>reduced cardiac output </li></ul><ul><li>drugs or nonpharmacologic : </li></ul><ul><li>- pacemaker, cardioversion, catheter ablation, surgery </li></ul>ANTI – ARRHYTHMIC DRUGS
    3. 3. ELECTRO-PHYSIOLOGY OF NORMAL CARDIAC RHYTHM <ul><li>SA node </li></ul>AV node ATRIA His-Purkinje System VENTRICLES ANTI – ARRHYTHMIC DRUGS
    4. 4. IONIC BASIS OF MEMBRANE ELECTRICAL ACTIVITY <ul><li>Transmembrane potential of cardiac cells is determined by the concentrations of the ff. ions: </li></ul><ul><ul><li>Sodium, Potassium, Calcium </li></ul></ul><ul><li>The movement of these ions produces currents that form the basis of the cardiac action potential </li></ul>ANTI – ARRHYTHMIC DRUGS
    5. 5. PHASES OF ACTION POTENTIAL <ul><li>Phase 0 </li></ul><ul><li>>Rapid depolarization </li></ul><ul><li>>Opening fast Na+ </li></ul><ul><li>channels -> Na+ rushes in ->depolarization </li></ul>Phase 1 >Limited depolarization >Inactivation of fast Na+ channels -> Na+ ion conc equalizes >↑ K+ efflux & Cl- influx Phase 2 >Plateau Stage >Cell less permeable to Na+ >Ca++ influx through slow Ca++ channels >K+ begins to leave cell Phase 3 >Rapid repolarization >Na+ gates closed >K+ efflux >Inactivation of slow Ca++ channels Phase 4 >Resting Membrane Potential >High K+ efflux >Ca++ influx ANTI – ARRHYTHMIC DRUGS
    6. 6. MECHANISMS OF ARRHYTHMIA <ul><li>ARRHYTHMIA – absence of rhythm </li></ul><ul><li>DYSRRHYTHMIA – abnormal rhythm </li></ul>ARRHYTHMIAS result from: <ul><li>Disturbance in Impulse Formation </li></ul><ul><li>2. Disturbance in Impulse Conduction </li></ul><ul><li>Block results from severely depressed conduction </li></ul><ul><li>Re-entry or circus movement / daughter impulse </li></ul>ANTI – ARRHYTHMIC DRUGS
    7. 7. FACTORS PRECIPITATING CARDIAC ARRHYTHMIAS: <ul><li>1. Ischemia </li></ul><ul><ul><li>pH & electrolyte abnormalities </li></ul></ul><ul><ul><li>80% – 90% asstd with MI </li></ul></ul><ul><li>2. Excessive myocardial fiber stretch/ scarred/ diseased cardiac tissue </li></ul><ul><li>3. Excessive discharge or sensitivity to autonomic transmitters </li></ul><ul><li>4. Excessive exposure to foreign chemicals & toxic substances </li></ul><ul><ul><li>20% - 50% asstd with General Anesthesia </li></ul></ul><ul><ul><li>10% - 20% asstd with Digitalis toxicity </li></ul></ul>ANTI – ARRHYTHMIC DRUGS
    8. 8. <ul><li>Supraventricular: </li></ul><ul><li>- Atrial Tachycardia </li></ul><ul><li>- Paroxysmal Tachycardia </li></ul><ul><li>Multifocal Atrial Tachycardia </li></ul><ul><li>- Atrial Fibrillation </li></ul><ul><li>- Atrial Flutter </li></ul><ul><li>Ventricular: </li></ul><ul><li>Wolff-Parkinson-White (preexcitation syndrome) </li></ul><ul><li>Ventricular Tachycardia </li></ul><ul><li>Ventricular Fibrillation </li></ul><ul><li>Premature Ventricular Contraction </li></ul>ARRHYTHMIAS: ANTI – ARRHYTHMIC DRUGS
    9. 9. CLASS I: Sodium Channel Blocking Drugs <ul><li>IA - lengthen AP duration </li></ul><ul><ul><ul><li>- Intermediate interaction with Na+ channels </li></ul></ul></ul><ul><ul><ul><li>- Quinidine, Procainamide, Disopyramide </li></ul></ul></ul><ul><li>IB - shorten AP duration </li></ul><ul><li>- rapid interaction with Na+ channels </li></ul><ul><li>- Lidocaine, Mexiletene, Tocainide, Phenytoin </li></ul><ul><li>IC - no effect or minimal  AP duration </li></ul><ul><li>- slow interaction with Na+ channels </li></ul><ul><li>- Flecainide, Propafenone, Moricizine </li></ul>ANTI – ARRHYTHMIC DRUGS
    10. 10. <ul><li>Increase AV nodal conduction </li></ul><ul><li>Increase PR interval </li></ul><ul><li>Prolong AV refractoriness </li></ul><ul><li>Reduce adrenergic activity </li></ul><ul><li>Propranolol, Esmolol, Metoprolol, Sotalol </li></ul>CLASS II: BETA-BLOCKING AGENTS ANTI – ARRHYTHMIC DRUGS
    11. 11. <ul><li>Prolong effective refractory period by prolonging Action Potential </li></ul><ul><ul><li>Amiodarone - Ibutilide </li></ul></ul><ul><ul><li>Bretylium - Dofetilide </li></ul></ul><ul><ul><li>Sotalol </li></ul></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS ANTI – ARRHYTHMIC DRUGS
    12. 12. CLASS IV: CALCIUM CHANNEL BLOCKERS <ul><li>Blocks cardiac calcium currents </li></ul><ul><li>-> slow conduction </li></ul><ul><li>-> increase refractory period </li></ul><ul><li>*esp. in Ca++ dependent tissues (i.e. AV node) </li></ul><ul><li>Verapamil, Diltiazem, Bepridil </li></ul>ANTI – ARRHYTHMIC DRUGS
    13. 13. Miscellaneous: <ul><li>ADENOSINE -> inhibits AV conduction & increases AV refractory period </li></ul><ul><li>DIGITALIS -> Indirectly alters autonomic outflow </li></ul><ul><li>MAGNESIUM -> Na+/K+ ATPase, Na+, K+, Ca++ channels </li></ul><ul><li>POTASSIUM -> normalize K+ gradients </li></ul>ANTI – ARRHYTHMIC DRUGS
    14. 14. <ul><li>Depress pacemaker rate </li></ul><ul><li>Depress conduction & excitability </li></ul><ul><li>Slows repolarization & lengthens AP duration </li></ul><ul><li>-> due to K+ channel blockade with reduction of repolarizing outward current -> reduce maximum reentry frequency -> slows tachycardia </li></ul><ul><li>(+) alpha adrenergic blocking properties -> vasodilatation & reflex ↑ SA node rate </li></ul>CLASS I: Sodium Channel Blocking Drugs CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS
    15. 15. CLASS I: SODIUM CHANNEL BLOCKERS <ul><li>Pharmacokinetics: </li></ul><ul><ul><li>Oral -> rapid GI absorption </li></ul></ul><ul><ul><li>80% plasma protein binding </li></ul></ul><ul><ul><li>20% excreted unchanged in the urine -> enhanced by acidity </li></ul></ul><ul><ul><li>t½ = 6 hours </li></ul></ul><ul><ul><li>Parenteral -> hypotension </li></ul></ul><ul><li>Dosage: 0.2 to 0.6 gm 2-4X a day </li></ul>CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS
    16. 16. CLASS I: SODIUM CHANNEL BLOCKERS <ul><li>Therapeutic Uses: </li></ul><ul><ul><li>Atrial flutter & fibrillation </li></ul></ul><ul><ul><li>Ventricular tachycardia </li></ul></ul><ul><ul><li>IV treatment of malaria </li></ul></ul><ul><li>Drug Interaction: </li></ul><ul><ul><li>Increases digoxin plasma levels </li></ul></ul>CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS
    17. 17. CLASS I: SODIUM CHANNEL BLOCKERS <ul><li>Toxicity: </li></ul><ul><ul><li>Antimuscarinic actions -> inh. vagal effects </li></ul></ul><ul><ul><li>Quinidine syncope (lightheadedness, fainting) </li></ul></ul><ul><ul><li>Ppt. arrhythmia or asystole </li></ul></ul><ul><ul><li>Depress contractility & ↓ BP </li></ul></ul><ul><ul><li>Widening QRS duration </li></ul></ul><ul><ul><li>Diarrhea , nausea, vomiting </li></ul></ul><ul><ul><li>Cinchonism (HA, dizziness, tinnitus) </li></ul></ul><ul><ul><li>Rare: rashes, fever, hepatitis, thrombocytopenia,etc </li></ul></ul>CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS
    18. 18. <ul><li>Less effective in suppressing abnormal ectopic pacemaker activity </li></ul><ul><li>More effective Na+ channel blockers in depolarized cells </li></ul><ul><li>Less prominent antimuscarinic action </li></ul><ul><li>(+) ganglionic blocking properties -> ↓PVR -> hypotension (severe if rapid IV or with severe LV dysfunction) </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS
    19. 19. <ul><li>PHARMACOKINETICS: </li></ul><ul><li>Oral, IV, IM </li></ul><ul><li>N-acetylprocainamide (NAPA) -> major metabolite </li></ul><ul><li>Metabolism: hepatic </li></ul><ul><li>Elimination: renal </li></ul><ul><li>t½ = 3 to 4 hrs. </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS
    20. 20. <ul><li>Dosage: </li></ul><ul><li>Loading IV – 12 mg/kg at 0.3 mg/kg/min or less rapidly </li></ul><ul><li>Maintenance – 2 to 5 mg/min </li></ul><ul><li>Therapeutic Use: </li></ul><ul><li>2 nd DOC in most CCU for the treatment of sustained ventricular arrhythmias asstd. with MI </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS
    21. 21. <ul><li>Toxicity: </li></ul><ul><li>- ppt. new arrhythmias </li></ul><ul><li>- LE-like syndrome </li></ul><ul><li>- pleuritis, pericarditis, parenchymal pulmonary disease </li></ul><ul><li>- ↑ ANA </li></ul><ul><li>- nausea, DHA, rash, fever, hepatitis, agranulocytosis </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS
    22. 22. <ul><li>More marked cardiac antimuscarinic effects than quinidine -> slows AV conduction </li></ul><ul><li>Pharmacokinetics: </li></ul><ul><li>- oral administration </li></ul><ul><li>- extensive protein binding </li></ul><ul><li>- t½ = 6 to 8 hrs </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI – ARRHYTHMIC DRUGS
    23. 23. <ul><li>Dosage : 150 mg TID up to 1 gm/day </li></ul><ul><li>Therapeutic Use : Ventricular arrhythmias </li></ul><ul><li>Toxicity: </li></ul><ul><li>- negative inotropic action (HF without prior myocardial dysfunction) </li></ul><ul><li>- Urinary retention, dry mouth, blurred vision, constipation, worsening glaucoma </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI – ARRHYTHMIC DRUGS
    24. 24. <ul><li>Approved only in serious ventricular arrhythmias </li></ul><ul><li>Broad spectrum of action on the </li></ul><ul><li>Very effective Na+ channel blocker but low affinity for activated channels </li></ul><ul><li>Markedly lengthens AP by blocking also K+ channels </li></ul><ul><li>Weak Ca++ channel blocker </li></ul><ul><li>Noncompetetive inhibitor of beta adrenoceptors </li></ul><ul><li>Powerful inhibitor of abnormal automaticity </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS
    25. 25. <ul><li>Slows sinus rate & AV conduction </li></ul><ul><li>Markedly prolongs the QT interval </li></ul><ul><li>Prolongs QRS duration </li></ul><ul><li>↑ atrial, AV nodal & ventricular refractory periods </li></ul><ul><li>Antianginal effects – due to noncompetetive α & β blocking property and block Ca++ influx in vascular sm.m. </li></ul><ul><li>Perivascular dilatation - α blocking property and Ca++ channel-inhibiting effects </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS
    26. 26. <ul><li>Pharmacokinetics: </li></ul><ul><li>> t ½ = 13 to 103 days </li></ul><ul><li>> effective plasma conc: 1-2 μ g/ml </li></ul><ul><li>Dosage: - Loading – 0.8 to 1.2 g daily </li></ul><ul><li>- Maintenance – 200 to 400 mg daily </li></ul><ul><li>Drug Interaction: reduce clearance of warfarin, theophylline, quinidine, procainamide, flecainide </li></ul><ul><li>Therapeutic Use: Supraventricular & Ventricular arrhythmias </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS
    27. 27. <ul><li>Toxicity: </li></ul><ul><li>- fatal pulmonary fibrosis </li></ul><ul><li>- yellowish-brown microcrystals corneal deposits </li></ul><ul><li>- photodermatitis </li></ul><ul><li>- grayish blue discoloration </li></ul><ul><li>- paresthesias, tremor, ataxia & headaches </li></ul><ul><li>- hypo - / hyperthyroidism </li></ul><ul><li>- Symptomatic bradycardia or heart block </li></ul><ul><li>- Ppt. heart failure </li></ul><ul><li>- Constipation, hepatocellular necrosis, inflam’n, fibrosis, hypotension </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS
    28. 28. <ul><li>Intravenous route only </li></ul><ul><li>Arrhythmias asstd with MI </li></ul><ul><li>Potent abnormal cardiac activity suppressor </li></ul><ul><li>Rapidly act exclusively on Na+ channels </li></ul><ul><li>Shorten AP, prolonged diastole -> extends time available for recovery </li></ul><ul><li>Suppresses electrical activity of DEPOLARIZED, ARRHYTHMOGENIC tissues only </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS
    29. 29. <ul><li>Pharmacokinetics: </li></ul><ul><li>- Extensive first-pass hepatic metabolism </li></ul><ul><ul><li>- t ½ = 1 to 2 hrs </li></ul></ul><ul><li>Dosages: loading- 150 to 200 mg </li></ul><ul><li>maintenance- 2-4 mg </li></ul><ul><li>Drug Interaction: </li></ul><ul><li>propranolol, cimetidine – reduce clearance </li></ul><ul><li>Therapeutic Use: </li></ul><ul><li>DOC for suppression of recurrences of ventricular tachycardia & fibrillation in the first few days after AMI. </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS
    30. 30. <ul><li>Toxicity: </li></ul><ul><ul><li>Ppt. SA nodal standstill or worsen impaired conduction </li></ul></ul><ul><ul><li>Exacerbates ventricular arrhythmias </li></ul></ul><ul><ul><li>Hypotension in HF </li></ul></ul><ul><ul><li>Neurologic: paresthesias, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions </li></ul></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS
    31. 31. <ul><li>Congeners of lidocaine </li></ul><ul><li>Oral route - resistant to first-pass hepatic metabolism </li></ul><ul><li>Tptic use: ventricular arrhythmias </li></ul><ul><li>Elimination t ½ = 8 to 20 hrs </li></ul><ul><li>Dosage: Mexiletene – 600 to 1200 mg/day </li></ul><ul><li>Tocainide – 800 to 2400 mg/day </li></ul><ul><li>S/E: tremors, blurred vision, lethargy, nausea, rash, fever, agranulocytosis </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: TOCAINIDE & MEXILETENE ANTI – ARRHYTHMIC DRUGS
    32. 32. <ul><li>Anti-convulsant with anti-arrhythmic properties </li></ul><ul><li>Suppresses ectopic pacemaker activity </li></ul><ul><li>Useful in digitalis-induced arrhythmia </li></ul><ul><li>Extensive, saturable first-pass hepatic metabolism </li></ul><ul><li>Highly protein bound </li></ul><ul><li>Toxicity: ataxia, nystagmus, mental confusion, serious dermatological & BM reactions, hypotension, gingival hyperplasia </li></ul><ul><li>D/I: Quinidine, Mexiletene, Digitoxin, Estrogen, Theophyllin, Vitamin D </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: PHENYTOIN ANTI – ARRHYTHMIC DRUGS
    33. 33. <ul><li>Potent blocker of Na+ & K+ channels </li></ul><ul><li>No antimuscarinic effects </li></ul><ul><li>Used in patients with supraventricular arrhythmias </li></ul><ul><li>Effective in PVC’s </li></ul><ul><li>Hepatic metabolism & renal elimination </li></ul><ul><li>Dosage: 100 to 200 mg bid </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: FLECAINIDE ANTI – ARRHYTHMIC DRUGS
    34. 34. <ul><li>(+) weak β -blocking activity </li></ul><ul><li>Potency ≈ flecainide </li></ul><ul><li>Average elim. t½ = 5 to 7 hrs. </li></ul><ul><li>Dosage: 450 – 900 mg TID </li></ul><ul><li>Tptic use: supraventricular arrhythmias </li></ul><ul><li>Adv. effects: metallic taste, constipation, arrhythmia exacerbation </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: PROPAFENONE ANTI – ARRHYTHMIC DRUGS
    35. 35. <ul><li>Antiarrhythmic phenothiazine derivative </li></ul><ul><li>Used in ventricular arrhythmias </li></ul><ul><li>Potent Na+ channel blocker </li></ul><ul><li>Donot prolong AP duration </li></ul><ul><li>Dosage: 200 to 300 mg orally tid </li></ul><ul><li>Adv. effects: dizziness, nausea </li></ul>CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: MORICIZINE ANTI – ARRHYTHMIC DRUGS
    36. 36. <ul><li>↑ AV nodal conduction time (↑ PR interval) </li></ul><ul><li>Prolong AV nodal refractoriness </li></ul><ul><ul><li>Useful in terminating reentrant arrhythmias that involve the AV node & in controlling ventricular response in AF & A.fib. </li></ul></ul><ul><li>Depresses phase 4 -> slows recovery of cells, slows conduction & decrease automaticity </li></ul><ul><li>Reduces HR, decrease IC Ca 2+ overload & inhibit after depolarization automaticity </li></ul><ul><li>Prevent recurrent infarction & sudden death in patients recovering from AMI </li></ul>CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS
    37. 37. <ul><li>“ membrane stabilizing effect” </li></ul><ul><ul><li>Exert Na+ channel blocking effect at high doses </li></ul></ul><ul><ul><li>Acebutolol, metoprolol, propranolol, labetalol, pindolol </li></ul></ul><ul><li>“ intrinsic sympathetic activity” </li></ul><ul><ul><li>Less antiarrhythmic effect </li></ul></ul><ul><ul><li>Acebutolol, celiprolol, carteolol, labetalol, pindolol </li></ul></ul><ul><li>Therapeutic indications: </li></ul><ul><ul><li>Supraventricular & ventricular arrhythmias </li></ul></ul><ul><ul><li>hypertension </li></ul></ul>CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS
    38. 38. <ul><li>Propranolol – (+) MSA </li></ul><ul><li>Acebutolol – as effective as quinidine in suppressing ventricular ectopic beats </li></ul><ul><li>Esmolol - short acting hence used primarily for intra-operative & other acute arrhythmias </li></ul><ul><li>Sotalol – has K+ channel blocking actions (class III) </li></ul>CLASS II: BETA ADRENOCEPTOR BLOCKERS Specific agents: ANTI – ARRHYTHMIC DRUGS
    39. 39. <ul><li>Drugs that prolong effective refractory period by prolonging action potential </li></ul><ul><li>Prolong AP by blocking K+ channels in cardiac muscle ( ↑ inward current through Na+ & Ca++ channels) </li></ul><ul><li>Quinidine & Amiodarone -> prolong AP duration </li></ul><ul><li>Bretylium & Sotalol -> prolong AP duration & refractory period </li></ul><ul><li>Ibutilide & Dofetilide -> “pure” class III agents </li></ul><ul><li>Reverse use-dependence </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS ANTI – ARRHYTHMIC DRUGS
    40. 40. <ul><li>Antihypertensive </li></ul><ul><li>Interferes with neuronal release of catecholamines </li></ul><ul><li>With direct antiarrhythmic properties </li></ul><ul><li>Lengthens ventricular AP duration & effective refractory period </li></ul><ul><li>Markedly ↑ strength of electrical stimulation needed to induce V.fib. & delays onset of fibrillation after acute coronary ligation </li></ul><ul><li>(+) inotropic action </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC DRUGS
    41. 41. <ul><li>Intravenous administration </li></ul><ul><li>Dosage: 5 mg/kg </li></ul><ul><li>Tptic Use: ventricular fibrillation </li></ul><ul><li>In emergency setting, during attempted resuscitation from ventricular fibrillation when lidocaine & cardioversion have failed </li></ul><ul><li>S/E: postural hypotension*** </li></ul><ul><li>ppt. ventricular arrhythmia </li></ul><ul><li>nausea & vomiting </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC DRUGS
    42. 42. <ul><li>Nonselective beta-blocker that also slows repolarization & prolongs AP duration </li></ul><ul><li>Effective antiarrhythmic agent </li></ul><ul><li>Used in supraventricular & ventricular arrhythmias in pediatric age group </li></ul><ul><li>Renal excretion </li></ul><ul><li>Dosage: 80 – 320 mg bid </li></ul><ul><li>Toxicity: torsades de pointes </li></ul><ul><li>beta-blockade symptoms </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS SOTALOL ANTI – ARRHYTHMIC DRUGS
    43. 43. <ul><li>Slows repolarization </li></ul><ul><li>Prolong cardiac action potentials </li></ul><ul><li>MOA: > enhance inward Na+ current </li></ul><ul><li>> by blocking I kr- </li></ul><ul><li>> both </li></ul><ul><li>routes: Oral, IV (1 mg over 10min) </li></ul><ul><li>Clin. Uses: atrial flutter, atrial fibrillation </li></ul><ul><li>Toxicity: Torsades de pointes </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS IBUTILIDE ANTI – ARRHYTHMIC DRUGS
    44. 44. <ul><li>A potential I kr- blocker </li></ul><ul><li>Dosage: 250-500 ug bid </li></ul><ul><li>Clin. Uses: Atrial flutter & fibrillation </li></ul><ul><li>Renal excretion </li></ul><ul><li>Toxicity: Torsade de pointes </li></ul>CLASS III: POTASSIUM CHANNEL BLOCKERS DOFETILIDE ANTI – ARRHYTHMIC DRUGS
    45. 45. <ul><li>Blocks both activated & inactivated calcium channels </li></ul><ul><li>Prolongs AV nodal conduction & effective refractory period </li></ul><ul><li>Suppress both early & delayed afterdepolarizations </li></ul><ul><li>May antagonize slow responses in severely depolarized tissues </li></ul><ul><li>Peripheral vasodilatation -> HPN & vasospastic disorders </li></ul>CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC DRUGS
    46. 46. <ul><li>Oral administration -> 20% bioavailability </li></ul><ul><li>t ½ = 7 hrs </li></ul><ul><li>Liver metabolism </li></ul><ul><li>Dosage: </li></ul><ul><li>IV: 5-10 mg every 4-6 hrs or infusion of 0.4 ug/kg/min </li></ul><ul><li>Oral: 120-640 mg daily, divided in 3-4 doses </li></ul><ul><li>Tptic use: SVT, AF, atrial fib, ventricular arrhythmias </li></ul><ul><li>Toxicity: AV block, can ppt. sinus arrest </li></ul><ul><li>constipation, lassitude, nervousness, peripheral edema </li></ul>CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC DRUGS
    47. 47. <ul><li>Similar efficacy to verapamil in supraventricular arrhythmias & rate control in atrial fibrillation </li></ul><ul><li>Bepridil </li></ul><ul><ul><li>AP & QT prolonging action-> ventricular arrhythmias but may ppt. torsade de pointes </li></ul></ul><ul><ul><li>Rarely used -> primarily to control refractory angina </li></ul></ul>CLASS IV: CALCIUM CHANNEL BLOCKERS DILTIAZEM & BEPRIDIL ANTI – ARRHYTHMIC DRUGS
    48. 48. <ul><li>Indirectly alters autonomic outflow by increasing parasympathetic tone & decreasing sympathetic tone </li></ul><ul><li>Results in decreased conduction time & increased refractory period in the AV node </li></ul>MISCELLANEOUS ANTIARRHYTHMIC AGENTS: DIGITALIS ANTI – ARRHYTHMIC DRUGS
    49. 49. <ul><li>A nucleoside that occurs naturally in the body </li></ul><ul><li>t ½ ≈ 10 seconds </li></ul><ul><li>MOA: enhances K+ conductance & inhibits cAMP-induced Ca++ influx -> results in marked hyperpolarization & suppression of Ca++-dependent AP </li></ul><ul><li>IV bolus: directly inhibits AV nodal conduction & ↑ AV nodal refractory period </li></ul>MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI – ARRHYTHMIC DRUGS
    50. 50. <ul><li>DOC for prompt conversion of paroxysmal SVT to sinus rhythm due to its high efficacy & very short duration of action </li></ul><ul><li>Dosage: 6-12 mg IV bolus </li></ul><ul><li>D/I: </li></ul><ul><ul><li>theophylline, caffeine – adenosine receptor blockers </li></ul></ul><ul><ul><li>Dipyridamole – adenosine uptake inhibitor </li></ul></ul><ul><li>Toxicity: flushing, SOB or chest burning, atrial fibrillation, headache, hypotension, nausea, paresthesia </li></ul>MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI – ARRHYTHMIC DRUGS
    51. 51. <ul><li>Effective in patients with recurrent episodes of torsades de pointes (MgSO 4 1 to 2 g IV) & in digitalis-induced arrhythmia </li></ul><ul><li>MOA: unknown -> influence Na+/K+ ATPase, Na+ channels, certain K+ and Ca++ channels </li></ul>MISCELLANEOUS ANTIARRHYTHMIC AGENTS: MAGNESIUM ANTI – ARRHYTHMIC DRUGS
    52. 52. <ul><li>Therapy directed toward normalizing K+ gradients & pools in the body </li></ul><ul><li>Effects of increasing serum K+: </li></ul><ul><ul><li>1. resting potential depolarizing action </li></ul></ul><ul><ul><li>2. membrane potential stabilizing action </li></ul></ul><ul><li>Hypokalemia: </li></ul><ul><ul><li>↑ risk of early & delayed afterdepolarization </li></ul></ul><ul><ul><li>↑ ectopic pacemaker activity esp if (+) digitalis </li></ul></ul><ul><li>Hyperkalemia: </li></ul><ul><ul><li>Depression of ectopic pacemakers </li></ul></ul><ul><ul><li>Slowing of conduction </li></ul></ul>ANTI – ARRHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS: POTASSIUM

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