Editd anti arrhythmic - Presentation Transcript



Editd anti arrhythmic - Presentation Transcript

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

2.

o Cardiac Arrhythmias:

▪ 25% treated with digitalis

▪ 50% anesthetized patients

▪ 80% patients with AMI

o reduced cardiac output

o drugs or nonpharmacologic :

o - pacemaker, cardioversion, catheter ablation, surgery

ANTI – ARRHYTHMIC DRUGS

3. ELECTRO-PHYSIOLOGY OF NORMAL CARDIAC RHYTHM

o SA node

AV node ATRIA His-Purkinje System VENTRICLES ANTI – ARRHYTHMIC DRUGS

4. IONIC BASIS OF MEMBRANE ELECTRICAL ACTIVITY

o Transmembrane potential of cardiac cells is determined by the concentrations of the ff. ions:

▪ Sodium, Potassium, Calcium

o The movement of these ions produces currents that form the basis of the cardiac action potential

ANTI – ARRHYTHMIC DRUGS

5. PHASES OF ACTION POTENTIAL

o Phase 0

o >Rapid depolarization

o >Opening fast Na+

o channels -> Na+ rushes in ->depolarization

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. MECHANISMS OF ARRHYTHMIA

o ARRHYTHMIA – absence of rhythm

o DYSRRHYTHMIA – abnormal rhythm

ARRHYTHMIAS result from:

o Disturbance in Impulse Formation

o 2. Disturbance in Impulse Conduction

o Block results from severely depressed conduction

o Re-entry or circus movement / daughter impulse

ANTI – ARRHYTHMIC DRUGS

7. FACTORS PRECIPITATING CARDIAC ARRHYTHMIAS:

o 1. Ischemia

▪ pH & electrolyte abnormalities

▪ 80% – 90% asstd with MI

o 2. Excessive myocardial fiber stretch/ scarred/ diseased cardiac tissue

o 3. Excessive discharge or sensitivity to autonomic transmitters

o 4. Excessive exposure to foreign chemicals & toxic substances

▪ 20% - 50% asstd with General Anesthesia

▪ 10% - 20% asstd with Digitalis toxicity

ANTI – ARRHYTHMIC DRUGS

8.

o Supraventricular:

o - Atrial Tachycardia

o - Paroxysmal Tachycardia

o Multifocal Atrial Tachycardia

o - Atrial Fibrillation

o - Atrial Flutter

o Ventricular:

o Wolff-Parkinson-White (preexcitation syndrome)

o Ventricular Tachycardia

o Ventricular Fibrillation

o Premature Ventricular Contraction

ARRHYTHMIAS: ANTI – ARRHYTHMIC DRUGS

9. CLASS I: Sodium Channel Blocking Drugs

o IA - lengthen AP duration

▪ - Intermediate interaction with Na+ channels

▪ - Quinidine, Procainamide, Disopyramide

o IB - shorten AP duration

o - rapid interaction with Na+ channels

o - Lidocaine, Mexiletene, Tocainide, Phenytoin

o IC - no effect or minimal  AP duration

o - slow interaction with Na+ channels

o - Flecainide, Propafenone, Moricizine

ANTI – ARRHYTHMIC DRUGS

10.

o Increase AV nodal conduction

o Increase PR interval

o Prolong AV refractoriness

o Reduce adrenergic activity

o Propranolol, Esmolol, Metoprolol, Sotalol

CLASS II: BETA-BLOCKING AGENTS ANTI – ARRHYTHMIC DRUGS

11.

o Prolong effective refractory period by prolonging Action Potential

▪ Amiodarone - Ibutilide

▪ Bretylium - Dofetilide

▪ Sotalol

CLASS III: POTASSIUM CHANNEL BLOCKERS ANTI – ARRHYTHMIC DRUGS

12. CLASS IV: CALCIUM CHANNEL BLOCKERS

o Blocks cardiac calcium currents

o -> slow conduction

o -> increase refractory period

o *esp. in Ca++ dependent tissues (i.e. AV node)

o Verapamil, Diltiazem, Bepridil

ANTI – ARRHYTHMIC DRUGS

13. Miscellaneous:

o ADENOSINE -> inhibits AV conduction & increases AV refractory period

o DIGITALIS -> Indirectly alters autonomic outflow

o MAGNESIUM -> Na+/K+ ATPase, Na+, K+, Ca++ channels

o POTASSIUM -> normalize K+ gradients

ANTI – ARRHYTHMIC DRUGS

14.

o Depress pacemaker rate

o Depress conduction & excitability

o Slows repolarization & lengthens AP duration

o -> due to K+ channel blockade with reduction of repolarizing outward current -> reduce maximum reentry frequency -> slows tachycardia

o (+) alpha adrenergic blocking properties -> vasodilatation & reflex ↑ SA node rate

CLASS I: Sodium Channel Blocking Drugs CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS

15. CLASS I: SODIUM CHANNEL BLOCKERS

o Pharmacokinetics:

▪ Oral -> rapid GI absorption

▪ 80% plasma protein binding

▪ 20% excreted unchanged in the urine -> enhanced by acidity

▪ t½ = 6 hours

▪ Parenteral -> hypotension

o Dosage: 0.2 to 0.6 gm 2-4X a day

CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS

16. CLASS I: SODIUM CHANNEL BLOCKERS

o Therapeutic Uses:

▪ Atrial flutter & fibrillation

▪ Ventricular tachycardia

▪ IV treatment of malaria

o Drug Interaction:

▪ Increases digoxin plasma levels

CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS

17. CLASS I: SODIUM CHANNEL BLOCKERS

o 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

CLASS IA: QUINIDINE ANTI – ARRHYTHMIC DRUGS

18.

o Less effective in suppressing abnormal ectopic pacemaker activity

o More effective Na+ channel blockers in depolarized cells

o Less prominent antimuscarinic action

o (+) ganglionic blocking properties -> ↓PVR -> hypotension (severe if rapid IV or with severe LV dysfunction)

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS

19.

o PHARMACOKINETICS:

o Oral, IV, IM

o N-acetylprocainamide (NAPA) -> major metabolite

o Metabolism: hepatic

o Elimination: renal

o t½ = 3 to 4 hrs.

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS

20.

o Dosage:

o Loading IV – 12 mg/kg at 0.3 mg/kg/min or less rapidly

o Maintenance – 2 to 5 mg/min

o Therapeutic Use:

o 2 nd DOC in most CCU for the treatment of sustained ventricular arrhythmias asstd. with MI

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS

21.

o Toxicity:

o - ppt. new arrhythmias

o - LE-like syndrome

o - pleuritis, pericarditis, parenchymal pulmonary disease

o - ↑ ANA

o - nausea, DHA, rash, fever, hepatitis, agranulocytosis

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI – ARRHYTHMIC DRUGS

22.

o More marked cardiac antimuscarinic effects than quinidine -> slows AV conduction

o Pharmacokinetics:

o - oral administration

o - extensive protein binding

o - t½ = 6 to 8 hrs

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI – ARRHYTHMIC DRUGS

23.

o Dosage : 150 mg TID up to 1 gm/day

o Therapeutic Use : Ventricular arrhythmias

o Toxicity:

o - negative inotropic action (HF without prior myocardial dysfunction)

o - Urinary retention, dry mouth, blurred vision, constipation, worsening glaucoma

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI – ARRHYTHMIC DRUGS

24.

o Approved only in serious ventricular arrhythmias

o Broad spectrum of action on the

o Very effective Na+ channel blocker but low affinity for activated channels

o Markedly lengthens AP by blocking also K+ channels

o Weak Ca++ channel blocker

o Noncompetetive inhibitor of beta adrenoceptors

o Powerful inhibitor of abnormal automaticity

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS

25.

o Slows sinus rate & AV conduction

o Markedly prolongs the QT interval

o Prolongs QRS duration

o ↑ atrial, AV nodal & ventricular refractory periods

o Antianginal effects – due to noncompetetive α & β blocking property and block Ca++ influx in vascular sm.m.

o Perivascular dilatation - α blocking property and Ca++ channel-inhibiting effects

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS

26.

o Pharmacokinetics:

o > t ½ = 13 to 103 days

o > effective plasma conc: 1-2 μ g/ml

o Dosage: - Loading – 0.8 to 1.2 g daily

o - Maintenance – 200 to 400 mg daily

o Drug Interaction: reduce clearance of warfarin, theophylline, quinidine, procainamide, flecainide

o Therapeutic Use: Supraventricular & Ventricular arrhythmias

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS

27.

o Toxicity:

o - fatal pulmonary fibrosis

o - yellowish-brown microcrystals corneal deposits

o - photodermatitis

o - grayish blue discoloration

o - paresthesias, tremor, ataxia & headaches

o - hypo - / hyperthyroidism

o - Symptomatic bradycardia or heart block

o - Ppt. heart failure

o - Constipation, hepatocellular necrosis, inflam’n, fibrosis, hypotension

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI – ARRHYTHMIC DRUGS

28.

o Intravenous route only

o Arrhythmias asstd with MI

o Potent abnormal cardiac activity suppressor

o Rapidly act exclusively on Na+ channels

o Shorten AP, prolonged diastole -> extends time available for recovery

o Suppresses electrical activity of DEPOLARIZED, ARRHYTHMOGENIC tissues only

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS

29.

o Pharmacokinetics:

o - Extensive first-pass hepatic metabolism

▪ - t ½ = 1 to 2 hrs

o Dosages: loading- 150 to 200 mg

o maintenance- 2-4 mg

o Drug Interaction:

o propranolol, cimetidine – reduce clearance

o Therapeutic Use:

o DOC for suppression of recurrences of ventricular tachycardia & fibrillation in the first few days after AMI.

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS

30.

o 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

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI – ARRHYTHMIC DRUGS

31.

o Congeners of lidocaine

o Oral route - resistant to first-pass hepatic metabolism

o Tptic use: ventricular arrhythmias

o Elimination t ½ = 8 to 20 hrs

o Dosage: Mexiletene – 600 to 1200 mg/day

o Tocainide – 800 to 2400 mg/day

o S/E: tremors, blurred vision, lethargy, nausea, rash, fever, agranulocytosis

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: TOCAINIDE & MEXILETENE ANTI – ARRHYTHMIC DRUGS

32.

o Anti-convulsant with anti-arrhythmic properties

o Suppresses ectopic pacemaker activity

o Useful in digitalis-induced arrhythmia

o Extensive, saturable first-pass hepatic metabolism

o Highly protein bound

o Toxicity: ataxia, nystagmus, mental confusion, serious dermatological & BM reactions, hypotension, gingival hyperplasia

o D/I: Quinidine, Mexiletene, Digitoxin, Estrogen, Theophyllin, Vitamin D

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: PHENYTOIN ANTI – ARRHYTHMIC DRUGS

33.

o Potent blocker of Na+ & K+ channels

o No antimuscarinic effects

o Used in patients with supraventricular arrhythmias

o Effective in PVC’s

o Hepatic metabolism & renal elimination

o Dosage: 100 to 200 mg bid

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: FLECAINIDE ANTI – ARRHYTHMIC DRUGS

34.

o (+) weak β -blocking activity

o Potency ≈ flecainide

o Average elim. t½ = 5 to 7 hrs.

o Dosage: 450 – 900 mg TID

o Tptic use: supraventricular arrhythmias

o Adv. effects: metallic taste, constipation, arrhythmia exacerbation

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: PROPAFENONE ANTI – ARRHYTHMIC DRUGS

35.

o Antiarrhythmic phenothiazine derivative

o Used in ventricular arrhythmias

o Potent Na+ channel blocker

o Donot prolong AP duration

o Dosage: 200 to 300 mg orally tid

o Adv. effects: dizziness, nausea

CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: MORICIZINE ANTI – ARRHYTHMIC DRUGS

36.

o ↑ AV nodal conduction time (↑ PR interval)

o Prolong AV nodal refractoriness

▪ Useful in terminating reentrant arrhythmias that involve the AV node & in controlling ventricular response in AF & A.fib.

o Depresses phase 4 -> slows recovery of cells, slows conduction & decrease automaticity

o Reduces HR, decrease IC Ca 2+ overload & inhibit after depolarization automaticity

o Prevent recurrent infarction & sudden death in patients recovering from AMI

CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS

37.

o “ membrane stabilizing effect”

▪ Exert Na+ channel blocking effect at high doses

▪ Acebutolol, metoprolol, propranolol, labetalol, pindolol

o “ intrinsic sympathetic activity”

▪ Less antiarrhythmic effect

▪ Acebutolol, celiprolol, carteolol, labetalol, pindolol

o Therapeutic indications:

▪ Supraventricular & ventricular arrhythmias

▪ hypertension

CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS

38.

o Propranolol – (+) MSA

o Acebutolol – as effective as quinidine in suppressing ventricular ectopic beats

o Esmolol - short acting hence used primarily for intra-operative & other acute arrhythmias

o Sotalol – has K+ channel blocking actions (class III)

CLASS II: BETA ADRENOCEPTOR BLOCKERS Specific agents: ANTI – ARRHYTHMIC DRUGS

39.

o Drugs that prolong effective refractory period by prolonging action potential

o Prolong AP by blocking K+ channels in cardiac muscle ( ↑ inward current through Na+ & Ca++ channels)

o Quinidine & Amiodarone -> prolong AP duration

o Bretylium & Sotalol -> prolong AP duration & refractory period

o Ibutilide & Dofetilide -> “pure” class III agents

o Reverse use-dependence

CLASS III: POTASSIUM CHANNEL BLOCKERS ANTI – ARRHYTHMIC DRUGS

40.

o Antihypertensive

o Interferes with neuronal release of catecholamines

o With direct antiarrhythmic properties

o Lengthens ventricular AP duration & effective refractory period

o Markedly ↑ strength of electrical stimulation needed to induce V.fib. & delays onset of fibrillation after acute coronary ligation

o (+) inotropic action

CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC DRUGS

41.

o Intravenous administration

o Dosage: 5 mg/kg

o Tptic Use: ventricular fibrillation

o In emergency setting, during attempted resuscitation from ventricular fibrillation when lidocaine & cardioversion have failed

o S/E: postural hypotension***

o ppt. ventricular arrhythmia

o nausea & vomiting

CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC DRUGS

42.

o Nonselective beta-blocker that also slows repolarization & prolongs AP duration

o Effective antiarrhythmic agent

o Used in supraventricular & ventricular arrhythmias in pediatric age group

o Renal excretion

o Dosage: 80 – 320 mg bid

o Toxicity: torsades de pointes

o beta-blockade symptoms

CLASS III: POTASSIUM CHANNEL BLOCKERS SOTALOL ANTI – ARRHYTHMIC DRUGS

43.

o Slows repolarization

o Prolong cardiac action potentials

o MOA: > enhance inward Na+ current

o > by blocking I kr-

o > both

o routes: Oral, IV (1 mg over 10min)

o Clin. Uses: atrial flutter, atrial fibrillation

o Toxicity: Torsades de pointes

CLASS III: POTASSIUM CHANNEL BLOCKERS IBUTILIDE ANTI – ARRHYTHMIC DRUGS

44.

o A potential I kr- blocker

o Dosage: 250-500 ug bid

o Clin. Uses: Atrial flutter & fibrillation

o Renal excretion

o Toxicity: Torsade de pointes

CLASS III: POTASSIUM CHANNEL BLOCKERS DOFETILIDE ANTI – ARRHYTHMIC DRUGS

45.

o Blocks both activated & inactivated calcium channels

o Prolongs AV nodal conduction & effective refractory period

o Suppress both early & delayed afterdepolarizations

o May antagonize slow responses in severely depolarized tissues

o Peripheral vasodilatation -> HPN & vasospastic disorders

CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC DRUGS

46.

o Oral administration -> 20% bioavailability

o t ½ = 7 hrs

o Liver metabolism

o Dosage:

o IV: 5-10 mg every 4-6 hrs or infusion of 0.4 ug/kg/min

o Oral: 120-640 mg daily, divided in 3-4 doses

o Tptic use: SVT, AF, atrial fib, ventricular arrhythmias

o Toxicity: AV block, can ppt. sinus arrest

o constipation, lassitude, nervousness, peripheral edema

CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC DRUGS

47.

o Similar efficacy to verapamil in supraventricular arrhythmias & rate control in atrial fibrillation

o Bepridil

▪ AP & QT prolonging action-> ventricular arrhythmias but may ppt. torsade de pointes

▪ Rarely used -> primarily to control refractory angina

CLASS IV: CALCIUM CHANNEL BLOCKERS DILTIAZEM & BEPRIDIL ANTI – ARRHYTHMIC DRUGS

48.

o Indirectly alters autonomic outflow by increasing parasympathetic tone & decreasing sympathetic tone

o Results in decreased conduction time & increased refractory period in the AV node

MISCELLANEOUS ANTIARRHYTHMIC AGENTS: DIGITALIS ANTI – ARRHYTHMIC DRUGS

49.

o A nucleoside that occurs naturally in the body

o t ½ ≈ 10 seconds

o MOA: enhances K+ conductance & inhibits cAMP-induced Ca++ influx -> results in marked hyperpolarization & suppression of Ca++-dependent AP

o IV bolus: directly inhibits AV nodal conduction & ↑ AV nodal refractory period

MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI – ARRHYTHMIC DRUGS

50.

o DOC for prompt conversion of paroxysmal SVT to sinus rhythm due to its high efficacy & very short duration of action

o Dosage: 6-12 mg IV bolus

o D/I:

▪ theophylline, caffeine – adenosine receptor blockers

▪ Dipyridamole – adenosine uptake inhibitor

o Toxicity: flushing, SOB or chest burning, atrial fibrillation, headache, hypotension, nausea, paresthesia

MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI – ARRHYTHMIC DRUGS

51.

o Effective in patients with recurrent episodes of torsades de pointes (MgSO 4 1 to 2 g IV) & in digitalis-induced arrhythmia

o MOA: unknown -> influence Na+/K+ ATPase, Na+ channels, certain K+ and Ca++ channels

MISCELLANEOUS ANTIARRHYTHMIC AGENTS: MAGNESIUM ANTI – ARRHYTHMIC DRUGS

52.

o Therapy directed toward normalizing K+ gradients & pools in the body

o Effects of increasing serum K+:

▪ 1. resting potential depolarizing action

▪ 2. membrane potential stabilizing action

o Hypokalemia:

▪ ↑ risk of early & delayed afterdepolarization

▪ ↑ ectopic pacemaker activity esp if (+) digitalis

o Hyperkalemia:

▪ Depression of ectopic pacemakers

▪ Slowing of conduction

ANTI – ARRHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS: POTASSIUM

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