Download 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
o
o
o
Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
Block results from severely depressed conduction
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
o
o
o
o
o
o
o
o
o
o
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
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
o
o
o
o
Increase AV nodal conduction
Increase PR interval
Prolong AV refractoriness
Reduce adrenergic activity
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
o
o
o
o
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
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
o
o
o
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)
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI –
ARRHYTHMIC DRUGS
19.
o
o
o
o
o
o
PHARMACOKINETICS:
Oral, IV, IM
N-acetylprocainamide (NAPA) -> major metabolite
Metabolism: hepatic
Elimination: renal
t½ = 3 to 4 hrs.
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI –
ARRHYTHMIC DRUGS
20.
o
o
o
o
o
Dosage:
Loading IV – 12 mg/kg at 0.3 mg/kg/min or less rapidly
Maintenance – 2 to 5 mg/min
Therapeutic Use:
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
o
o
o
o
o
Toxicity:
- ppt. new arrhythmias
- LE-like syndrome
- pleuritis, pericarditis, parenchymal pulmonary disease
- ↑ ANA
- nausea, DHA, rash, fever, hepatitis, agranulocytosis
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: PROCAINAMIDE ANTI –
ARRHYTHMIC DRUGS
22.
o
o
o
o
o
More marked cardiac antimuscarinic effects than quinidine -> slows AV conduction
Pharmacokinetics:
- oral administration
- extensive protein binding
- t½ = 6 to 8 hrs
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI –
ARRHYTHMIC DRUGS
23.
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: DISOPYRAMIDE ANTI –
ARRHYTHMIC DRUGS
24.
o
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI –
ARRHYTHMIC DRUGS
25.
o
o
o
o
o
o
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 - α blocking property and Ca++ channel-inhibiting effects
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI –
ARRHYTHMIC DRUGS
26.
o
o
o
o
o
Pharmacokinetics:
> t ½ = 13 to 103 days
> effective plasma conc: 1-2 μ g/ml
Dosage: - Loading – 0.8 to 1.2 g daily
- Maintenance – 200 to 400 mg daily
o
o
Drug Interaction: reduce clearance of warfarin, theophylline, quinidine, procainamide,
flecainide
Therapeutic Use: Supraventricular & Ventricular arrhythmias
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI –
ARRHYTHMIC DRUGS
27.
o
o
o
o
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IA: AMIODARONE ANTI –
ARRHYTHMIC DRUGS
28.
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: LIDOCAINE ANTI –
ARRHYTHMIC DRUGS
29.
o
o
o
o
o
o
o
o
Pharmacokinetics:
- Extensive first-pass hepatic metabolism
 - t ½ = 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.
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
o
o
o
o
o
o
Congeners of lidocaine
Oral route - resistant to first-pass hepatic metabolism
Tptic use: ventricular arrhythmias
Elimination t ½ = 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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: TOCAINIDE & MEXILETENE
ANTI – ARRHYTHMIC DRUGS
32.
o
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IB: PHENYTOIN ANTI –
ARRHYTHMIC DRUGS
33.
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: FLECAINIDE ANTI –
ARRHYTHMIC DRUGS
34.
o
o
o
o
o
o
(+) 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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: PROPAFENONE ANTI –
ARRHYTHMIC DRUGS
35.
o
o
o
o
o
o
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
CLASS I: SODIUM CHANNEL BLOCKERS CLASS IC: MORICIZINE ANTI –
ARRHYTHMIC DRUGS
36.
o
o
o
o
o
↑ 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 Ca 2+ overload & inhibit after depolarization automaticity
Prevent recurrent infarction & sudden death in patients recovering from AMI
CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS
37.
o
o
o
“ 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
CLASS II: BETA ADRENOCEPTOR BLOCKERS ANTI – ARRHYTHMIC DRUGS
38.
o
o
o
o
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)
CLASS II: BETA ADRENOCEPTOR BLOCKERS Specific agents: ANTI – ARRHYTHMIC
DRUGS
39.
o
o
o
o
o
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
o
Reverse use-dependence
CLASS III: POTASSIUM CHANNEL BLOCKERS ANTI – ARRHYTHMIC DRUGS
40.
o
o
o
o
o
o
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
CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC
DRUGS
41.
o
o
o
o
o
o
o
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
CLASS III: POTASSIUM CHANNEL BLOCKERS BRETYLIUM ANTI – ARRHYTHMIC
DRUGS
42.
o
o
o
o
o
o
o
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
CLASS III: POTASSIUM CHANNEL BLOCKERS SOTALOL ANTI – ARRHYTHMIC
DRUGS
43.
o
o
o
o
o
o
o
o
Slows repolarization
Prolong cardiac action potentials
MOA: > enhance inward Na+ current
> by blocking I kr> both
routes: Oral, IV (1 mg over 10min)
Clin. Uses: atrial flutter, atrial fibrillation
Toxicity: Torsades de pointes
CLASS III: POTASSIUM CHANNEL BLOCKERS IBUTILIDE ANTI – ARRHYTHMIC
DRUGS
44.
o
o
o
o
o
A potential I kr- blocker
Dosage: 250-500 ug bid
Clin. Uses: Atrial flutter & fibrillation
Renal excretion
Toxicity: Torsade de pointes
CLASS III: POTASSIUM CHANNEL BLOCKERS DOFETILIDE ANTI – ARRHYTHMIC
DRUGS
45.
o
o
o
o
o
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
CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC
DRUGS
46.
o
o
o
o
o
o
o
o
o
Oral administration -> 20% bioavailability
t ½ = 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
CLASS IV: CALCIUM CHANNEL BLOCKERS VERAPAMIL ANTI – ARRHYTHMIC
DRUGS
47.
o
o
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
CLASS IV: CALCIUM CHANNEL BLOCKERS DILTIAZEM & BEPRIDIL ANTI –
ARRHYTHMIC DRUGS
48.
o
o
Indirectly alters autonomic outflow by increasing parasympathetic tone & decreasing
sympathetic tone
Results in decreased conduction time & increased refractory period in the AV node
MISCELLANEOUS ANTIARRHYTHMIC AGENTS: DIGITALIS ANTI – ARRHYTHMIC
DRUGS
49.
o
o
o
o
A nucleoside that occurs naturally in the body
t ½ ≈ 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
MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI –
ARRHYTHMIC DRUGS
50.
o
o
o
o
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
MISCELLANEOUS ANTIARRHYTHMIC AGENTS: ADENOSINE ANTI –
ARRHYTHMIC DRUGS
51.
o
o
Effective in patients with recurrent episodes of torsades de pointes (MgSO 4 1 to 2 g
IV) & in digitalis-induced arrhythmia
MOA: unknown -> influence Na+/K+ ATPase, Na+ channels, certain K+ and Ca++
channels
MISCELLANEOUS ANTIARRHYTHMIC AGENTS: MAGNESIUM ANTI –
ARRHYTHMIC DRUGS
52.
o
o
o
o
Therapy directed toward normalizing K+ gradients & pools in the body
Effects of increasing serum K+:
 1. resting potential depolarizing action
 2. membrane potential stabilizing action
Hypokalemia:
 ↑ risk of early & delayed afterdepolarization
 ↑ ectopic pacemaker activity esp if (+) digitalis
Hyperkalemia:
 Depression of ectopic pacemakers
 Slowing of conduction
ANTI – ARRHYTHMIC DRUGS MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
POTASSIUM