ANTI-ARRHYTHMIC for mbbs bds bsc nursing

ANTI-ARRHYTHMIC for mbbs bds bsc nursing

1. ANTI-ARRHYTHMICANTI-ARRHYTHMIC
DRUGSDRUGS
DRN.RAVEENDRAKUMAR
M.D
ASSOCIATEPROFESSOR
ASRAM

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

4. 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
ANTI – ARRHYTHMIC DRUGS

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

6. 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
ANTI – ARRHYTHMIC DRUGS

7. 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:

8. 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
ANTI – ARRHYTHMIC DRUGS

9. 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

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

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

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

13. 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
ANTI – ARRHYTHMIC DRUGSANTI – ARRHYTHMIC DRUGS
CLASS I: Sodium Channel Blocking Drugs
CLASS IA: QUINIDINE

14. CLASS I: SODIUM CHANNEL BLOCKERS
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
ANTI – ARRHYTHMIC DRUGS
CLASS IA: QUINIDINE

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

16. CLASS I: SODIUM CHANNEL BLOCKERS
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
ANTI – ARRHYTHMIC DRUGS
CLASS IA: QUINIDINE

17. Less effective in suppressing abnormal ectopic
pacemaker activity
More effective Na+ channel blockers in
depolarized cells
Less prominent antimuscactirinic action
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE

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

19. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE

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

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

22. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: DISOPYRAMIDE

23. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: AMIODARONE

24. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: AMIODARONE

25. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: AMIODARONE

26. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: AMIODARONE

27. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE

28. 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.
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE

29. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE

30. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: TOCAINIDE & MEXILETENE

31. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: PHENYTOIN

32. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: FLECAINIDE

33. (+) 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: PROPAFENONE

34. 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
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: MORICIZINE

35. ↑ 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
ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS

36. “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
ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS

37. 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)
ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS
Specific agents:

38. 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
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS

39. 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
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
BRETYLIUM

40. 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
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
BRETYLIUM

41. 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
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
SOTALOL

42. 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
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
IBUTILIDE

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

44. 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
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
VERAPAMIL

45. 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
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
VERAPAMIL

46. 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
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
DILTIAZEM & BEPRIDIL

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

48. 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
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
ADENOSINE

49. 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
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
ADENOSINE

50. 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
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
MAGNESIUM

51. 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 – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
POTASSIUM