1 / 52

ANTI-ARRHYTHMIC DRUGS

ANTI-ARRHYTHMIC DRUGS. Ma. Janetth B. Serrano, M.D.,DPBA. ANTI – ARRHYTHMIC DRUGS. Cardiac Arrhythmias: 25% treated with digitalis 50% anesthetized patients 80% patients with AMI reduced cardiac output drugs or nonpharmacologic :

Télécharger la présentation

ANTI-ARRHYTHMIC DRUGS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. ANTI-ARRHYTHMICDRUGS Ma. Janetth B. Serrano, M.D.,DPBA

  2. ANTI – ARRHYTHMIC DRUGS • Cardiac Arrhythmias: • 25% treated with digitalis • 50% anesthetized patients • 80% patients with AMI • reduced cardiac output • drugs or nonpharmacologic: - pacemaker, cardioversion, catheter ablation, surgery

  3. ANTI – ARRHYTHMIC DRUGS ELECTRO-PHYSIOLOGY OF NORMAL CARDIAC RHYTHM SA node ATRIA AV node His-Purkinje System VENTRICLES

  4. ANTI – ARRHYTHMIC DRUGS IONIC BASIS OF MEMBRANE ELECTRICAL ACTIVITY • Transmembrane potential of cardiac cells is determined by the concentrations of the ff. ions: • Sodium, Potassium, Calcium • The movement of these ions produces currents that form the basis of the cardiac action potential

  5. ANTI – ARRHYTHMIC DRUGS PHASES OF ACTION POTENTIAL Phase 0 >Rapid depolarization >Opening fast Na+ channels→ Na+ rushes in →depolarization Phase 2 >Plateau Stage >Cell less permeable to Na+ >Ca++ influx through slow Ca++ channels >K+ begins to leave cell Phase 1 >Limited depolarization >Inactivation of fast Na+ channels→ Na+ ion conc equalizes >↑ K+ efflux & Cl- influx Phase 3 >Rapid repolarization >Na+ gates closed >K+ efflux >Inactivation of slow Ca++ channels Phase 4 >Resting Membrane Potential >High K+ efflux >Ca++ influx

  6. ANTI – ARRHYTHMIC DRUGS MECHANISMS OF ARRHYTHMIA ARRHYTHMIA – absence of rhythm DYSRRHYTHMIA – abnormal rhythm ARRHYTHMIAS result from: • Disturbance in Impulse Formation 2. Disturbance in Impulse Conduction • Block results from severely depressed conduction • Re-entry or circus movement / daughter impulse

  7. ANTI – ARRHYTHMIC DRUGS FACTORS PRECIPITATING CARDIAC ARRHYTHMIAS: 1. Ischemia • pH & electrolyte abnormalities • 80% – 90% asstd with MI 2. Excessive myocardial fiber stretch/ scarred/ diseased cardiac tissue 3. Excessive discharge or sensitivity to autonomic transmitters 4. Excessive exposure to foreign chemicals & toxic substances • 20% - 50% asstd with General Anesthesia • 10% - 20% asstd with Digitalis toxicity

  8. Supraventricular: - Atrial Tachycardia - Paroxysmal Tachycardia Multifocal Atrial Tachycardia - Atrial Fibrillation - Atrial Flutter Ventricular: Wolff-Parkinson-White (preexcitation syndrome) Ventricular Tachycardia Ventricular Fibrillation Premature Ventricular Contraction ANTI – ARHYTHMIC DRUGS ARRHYTHMIAS:

  9. ANTI – ARRHYTHMIC DRUGS CLASS I: Sodium Channel Blocking Drugs • IA - lengthen AP duration - Intermediate interaction with Na+ channels - Quinidine, Procainamide, Disopyramide • IB - shorten AP duration - rapid interaction with Na+ channels - Lidocaine, Mexiletene, Tocainide, Phenytoin • IC - no effect or minimal  AP duration - slow interaction with Na+ channels - Flecainide, Propafenone, Moricizine

  10. ANTI – ARRHYTHMIC DRUGS CLASS II: BETA-BLOCKING AGENTS • Increase AV nodal conduction • Increase PR interval • Prolong AV refractoriness • Reduce adrenergic activity • Propranolol, Esmolol, Metoprolol, Sotalol

  11. ANTI – ARRHYTHMIC DRUGS ANTI – ARRHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS • Prolong effective refractory period by prolonging Action Potential • Amiodarone - Ibutilide • Bretylium - Dofetilide • Sotalol

  12. ANTI – ARRHYTHMIC DRUGS ANTI – ARRHYTHMIC DRUGS CLASS IV: CALCIUM CHANNEL BLOCKERS • Blocks cardiac calcium currents → slow conduction → increase refractory period *esp. in Ca++ dependent tissues (i.e. AV node) • Verapamil, Diltiazem, Bepridil

  13. ANTI – ARRHYTHMIC DRUGS Miscellaneous: • ADENOSINE → inhibits AV conduction & increases AV refractory period • MAGNESIUM→ Na+/K+ ATPase, Na+, K+, Ca++ channels • POTASSIUM → normalize K+ gradients

  14. ANTI – ARRHYTHMIC DRUGS ANTI – ARRHYTHMIC DRUGS CLASS I: Sodium Channel Blocking Drugs CLASS IA: QUINIDINE • Depress pacemaker rate • Depress conduction & excitability • Slows repolarization & lengthens AP duration → due to K+ channel blockade with reduction of repolarizing outward current → reduce maximum reentry frequency → slows tachycardia • (+) alpha adrenergic blocking properties → vasodilatation & reflex ↑ SA node rate

  15. ANTI – ARRHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: QUINIDINE • Pharmacokinetics: • Oral → rapid GI absorption • 80% plasma protein binding • 20% excreted unchanged in the urine → enhanced by acidity • t½ = 6 hours • Parenteral → hypotension • Dosage: 0.2 to 0.6 gm 2-4X a day

  16. ANTI – ARRHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: QUINIDINE • Therapeutic Uses: • Atrial flutter & fibrillation • Ventricular tachycardia • IV treatment of malaria • Drug Interaction: • Increases digoxin plasma levels

  17. ANTI – ARRHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: QUINIDINE • Toxicity: • Antimuscarinic actions → inh. vagal effects • Quinidine syncope (lightheadedness, fainting) • Ppt. arrhythmia or asystole • Depress contractility & ↓ BP • Widening QRS duration • Diarrhea, nausea, vomiting • Cinchonism (HA, dizziness, tinnitus) • Rare: rashes, fever, hepatitis, thrombocytopenia,etc

  18. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE • Less effective in suppressing abnormal ectopic pacemaker activity • More effective Na+ channel blockers in depolarized cells • Less prominent antimuscarinic action • (+) ganglionic blocking properties → ↓PVR → hypotension (severe if rapid IV or with severe LV dysfunction)

  19. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE PHARMACOKINETICS: • Oral, IV, IM • N-acetylprocainamide (NAPA) → major metabolite • Metabolism: hepatic • Elimination: renal • t½ = 3 to 4 hrs.

  20. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE • Dosage: Loading IV – 12 mg/kg at 0.3 mg/kg/min or less rapidly Maintenance – 2 to 5 mg/min • Therapeutic Use: 2nd DOC in most CCU for the treatment of sustained ventricular arrhythmias asstd. with MI

  21. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE • Toxicity: - ppt. new arrhythmias - LE-like syndrome - pleuritis, pericarditis, parenchymal pulmonary disease - ↑ ANA - nausea, DHA, rash, fever, hepatitis, agranulocytosis

  22. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE • More marked cardiac antimuscarinic effects than quinidine → slows AV conduction • Pharmacokinetics: - oral administration - extensive protein binding - t½ = 6 to 8 hrs

  23. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE • Dosage: 150 mg TID up to 1 gm/day • Therapeutic Use: Ventricular arrhythmias • Toxicity: - negative inotropic action (HF without prior myocardial dysfunction) - Urinary retention, dry mouth, blurred vision, constipation, worsening glaucoma

  24. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE • Approved only in serious ventricular arrhythmias • Broad spectrum of action on the • Very effective Na+ channel blocker but low affinity for activated channels • Markedly lengthens AP by blocking also K+ channels • Weak Ca++ channel blocker • Noncompetetive inhibitor of beta adrenoceptors • Powerful inhibitor of abnormal automaticity

  25. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE • Slows sinus rate & AV conduction • Markedly prolongs the QT interval • Prolongs QRS duration • ↑ atrial, AV nodal & ventricular refractory periods • Antianginal effects – due to noncompetetive α& β blocking property and block Ca++ influx in vascular sm.m. • Perivascular dilatation - αblocking property and Ca++ channel-inhibiting effects

  26. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE • Pharmacokinetics: > t½ = 13 to 103 days > effective plasma conc: 1-2 μg/ml • Dosage: - Loading – 0.8 to 1.2 g daily - Maintenance – 200 to 400 mg daily • Drug Interaction: reduce clearance of warfarin, theophylline, quinidine, procainamide, flecainide • Therapeutic Use: Supraventricular & Ventricular arrhythmias

  27. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE • Toxicity: - fatal pulmonary fibrosis - yellowish-brown microcrystals corneal deposits - photodermatitis - grayish blue discoloration - paresthesias, tremor, ataxia & headaches - hypo - / hyperthyroidism - Symptomatic bradycardia or heart block - Ppt. heart failure - Constipation, hepatocellular necrosis, inflam’n, fibrosis, hypotension

  28. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE • Intravenous route only • Arrhythmias asstd with MI • Potent abnormal cardiac activity suppressor • Rapidly act exclusively on Na+ channels • Shorten AP, prolonged diastole → extends time available for recovery • Suppresses electrical activity of DEPOLARIZED, ARRHYTHMOGENIC tissues only

  29. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE • Pharmacokinetics: - Extensive first-pass hepatic metabolism - t½ = 1 to 2 hrs • Dosages: loading- 150 to 200 mg maintenance- 2-4 mg • Drug Interaction: propranolol, cimetidine – reduce clearance • Therapeutic Use: DOC for suppression of recurrences of ventricular tachycardia & fibrillation in the first few days after AMI.

  30. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE • Toxicity: • Ppt. SA nodal standstill or worsen impaired conduction • Exacerbates ventricular arrhythmias • Hypotension in HF • Neurologic: paresthesias, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions

  31. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: TOCAINIDE & MEXILETENE • Congeners of lidocaine • Oral route - resistant to first-pass hepatic metabolism • Tptic use: ventricular arrhythmias • Elimination t½ = 8 to 20 hrs • Dosage: Mexiletene – 600 to 1200 mg/day Tocainide – 800 to 2400 mg/day • S/E: tremors, blurred vision, lethargy, nausea, rash, fever, agranulocytosis

  32. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: PHENYTOIN • Anti-convulsant with anti-arrhythmic properties • Suppresses ectopic pacemaker activity • Useful in digitalis-induced arrhythmia • Extensive, saturable first-pass hepatic metabolism • Highly protein bound • Toxicity: ataxia, nystagmus, mental confusion, serious dermatological & BM reactions, hypotension, gingival hyperplasia • D/I: Quinidine, Mexiletene, Digitoxin, Estrogen, Theophyllin, Vitamin D

  33. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: FLECAINIDE • Potent blocker of Na+ & K+ channels • No antimuscarinic effects • Used in patients with supraventricular arrhythmias • Effective in PVC’s • Hepatic metabolism & renal elimination • Dosage: 100 to 200 mg bid

  34. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: PROPAFENONE • (+) weak β-blocking activity • Potency ≈ flecainide • Average elim. t½ = 5 to 7 hrs. • Dosage: 450 – 900 mg TID • Tptic use: supraventricular arrhythmias • Adv. effects: metallic taste, constipation, arrhythmia exacerbation

  35. ANTI – ARHYTHMIC DRUGS CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: MORICIZINE • Antiarrhythmic phenothiazine derivative • Used in ventricular arrhythmias • Potent Na+ channel blocker • Donot prolong AP duration • Dosage: 200 to 300 mg orally tid • Adv. effects: dizziness, nausea

  36. ANTI – ARHYTHMIC DRUGS CLASS II: BETA ADRENOCEPTOR BLOCKERS • ↑ AV nodal conduction time (↑ PR interval) • Prolong AV nodal refractoriness • Useful in terminating reentrant arrhythmias that involve the AV node & in controlling ventricular response in AF & A.fib. • Depresses phase 4 → slows recovery of cells, slows conduction & decrease automaticity • Reduces HR, decrease IC Ca2+ overload & inhibit after depolarization automaticity • Prevent recurrent infarction & sudden death in patients recovering from AMI

  37. ANTI – ARHYTHMIC DRUGS CLASS II: BETA ADRENOCEPTOR BLOCKERS • “membrane stabilizing effect” • Exert Na+ channel blocking effect at high doses • Acebutolol, metoprolol, propranolol, labetalol, pindolol • “intrinsic sympathetic activity” • Less antiarrhythmic effect • Acebutolol, celiprolol, carteolol, labetalol, pindolol • Therapeutic indications: • Supraventricular & ventricular arrhythmias • hypertension

  38. ANTI – ARHYTHMIC DRUGS CLASS II: BETA ADRENOCEPTOR BLOCKERS Specific agents: • Propranolol – (+) MSA • Acebutolol – as effective as quinidine in suppressing ventricular ectopic beats • Esmolol - short acting hence used primarily for intra-operative & other acute arrhythmias • Sotalol – has K+ channel blocking actions (class III)

  39. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS • Drugs that prolong effective refractory period by prolonging action potential • Prolong AP by blocking K+ channels in cardiac muscle (↑ inward current through Na+ & Ca++ channels) • Quinidine & Amiodarone → prolong AP duration • Bretylium & Sotalol → prolong AP duration & refractory period • Ibutilide & Dofetilide→ “pure” class III agents • Reverse use-dependence

  40. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM • Antihypertensive • Interferes with neuronal release of catecholamines • With direct antiarrhythmic properties • Lengthens ventricular AP duration & effective refractory period • Markedly ↑ strength of electrical stimulation needed to induce V.fib. & delays onset of fibrillation after acute coronary ligation • (+) inotropic action

  41. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS • Intravenous administration • Dosage: 5 mg/kg • Tptic Use: ventricular fibrillation • In emergency setting, during attempted resuscitation from ventricular fibrillation when lidocaine & cardioversion have failed • S/E: postural hypotension*** ppt. ventricular arrhythmia nausea & vomiting BRETYLIUM

  42. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS SOTALOL • Nonselective beta-blocker that also slows repolarization & prolongs AP duration • Effective antiarrhythmic agent • Used in supraventricular & ventricular arrhythmias in pediatric age group • Renal excretion • Dosage: 80 – 320 mg bid • Toxicity: torsades de pointes beta-blockade symptoms

  43. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS • Slows repolarization • Prolong cardiac action potentials • MOA: > enhance inward Na+ current > by blocking Ikr- > both • routes: Oral, IV (1 mg over 10min) • Clin. Uses: atrial flutter, atrial fibrillation • Toxicity: Torsades de pointes IBUTILIDE

  44. ANTI – ARHYTHMIC DRUGS CLASS III: POTASSIUM CHANNEL BLOCKERS DOFETILIDE • A potential Ikr- blocker • Dosage: 250-500 ug bid • Clin. Uses: Atrial flutter & fibrillation • Renal excretion • Toxicity: Torsade de pointes

  45. ANTI – ARHYTHMIC DRUGS CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL • Blocks both activated & inactivated calcium channels • Prolongs AV nodal conduction & effective refractory period • Suppress both early & delayed afterdepolarizations • May antagonize slow responses in severely depolarized tissues • Peripheral vasodilatation → HPN & vasospastic disorders

  46. ANTI – ARHYTHMIC DRUGS CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL • Oral administration → 20% bioavailability • t½ = 7 hrs • Liver metabolism • Dosage: IV: 5-10 mg every 4-6 hrs or infusion of 0.4 ug/kg/min Oral: 120-640 mg daily, divided in 3-4 doses • Tptic use: SVT, AF, atrial fib, ventricular arrhythmias • Toxicity: AV block, can ppt. sinus arrest constipation, lassitude, nervousness, peripheral edema

  47. ANTI – ARHYTHMIC DRUGS CLASS IV: CALCIUM CHANNEL BLOCKERS • Similar efficacy to verapamil in supraventricular arrhythmias & rate control in atrial fibrillation • Bepridil • AP & QT prolonging action→ ventricular arrhythmias but may ppt. torsade de pointes • Rarely used → primarily to control refractory angina DILTIAZEM & BEPRIDIL

  48. ANTI – ARHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS: DIGITALIS • Indirectly alters autonomic outflow by increasing parasympathetic tone & decreasing sympathetic tone • Results in decreased conduction time & increased refractory period in the AV node

  49. ANTI – ARHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE • A nucleoside that occurs naturally in the body • t½ ≈ 10 seconds • MOA: enhances K+ conductance & inhibits cAMP-induced Ca++ influx → results in marked hyperpolarization & suppression of Ca++-dependent AP • IV bolus: directly inhibits AV nodal conduction & ↑ AV nodal refractory period

  50. ANTI – ARHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE • DOC for prompt conversion of paroxysmal SVT to sinus rhythm due to its high efficacy & very short duration of action • Dosage: 6-12 mg IV bolus • D/I: • theophylline, caffeine – adenosine receptor blockers • Dipyridamole – adenosine uptake inhibitor • Toxicity: flushing, SOB or chest burning, atrial fibrillation, headache, hypotension, nausea, paresthesia

More Related