A short review by Dr. SWETHA YOUTUBE LINK FOR AUDIO AND VIDEO-https://youtu.be/cj0bCwx4A_Y

1. Dr . SWETHA

2. INTRODUCTION:
• CLASS -1 ANTI-ARRHYTHMIC DRUGS are also known as Sodium Channel
Blockers.

3. CLASSIFICATION
• Class-1 Anti- Arrhythmic drugs are further classified as 1a, 1b, 1c based on their
mechanism of action, effect on Action Potential Duration, binding and
dissociation from sodium channels.
CLASS1a
• Sodium channel
blockade with
prolonged
refractoriness.
CLASS 1b
• Sodium channel
blockade with
shortened
refractoriness.
CLASS1c
• 1c-Sodium channel
blockade with
minimal effect on
refractoriness.

4. Quinidine
Disopyramide
Procainamide
Lignocaine
Mexiletine
Phenytoin
Tocainide
Propafenone
Moricizine
Encainide
Flecainide
Queen D P
L. M. P. Test
PM’s
EF
Class 1a
Class 1b
Class 1c
DRUGS

5. P
QRS
T
NORMAL
PHYSIOLOGY
P-0:Na+entry into the cell
P-1: some K+leaving the cell
P-2: Ca+2 entry into the cell
P-3: K+leaving the cell
rapidly
P-0:Rapid depolarization
P-1:Early Repolarization
P-2:Plateau Phase
P-3:Rapid Repolarization
P-4:Resting membrane
state
QRS Complex :ventricular
contraction, P-0
T wave : ventricular relaxation, P-3
QT interval-Beginning of
depolarization to end of
repolarization
QT interval = Action Potential
Duration
Q
R
S
QT interval

6. MECHANISM OF ACTION
CLASS 1a ANTI- ARRHYTHMIC DRUGS
Membrane
potential
Time
Class 1a - Moderate depression of slope of
depolarization
Normal
ERP
AP
D
P
Q
R
S
T
Widened QRS complex and Prolonged QT

7. CLASS-1b ANTI- ARRHYTHMIC DRUGS
MECHANISM OF ACTION Cont….d
Membrane
potential
Time
Class 1b-slight depression of slope of
depolarization
Normal
ERP
AP
D
P
Q
R
S
T
QT
interval
Widened QRS complex
and shortened QT
interval

8. CLASS 1c ANTI- ARRHYTHMIC DRUGS
MECHANISM OF ACTION Cont….d
Membrane
potential
Time
Normal
Normal
ERP
Normal
APD
P
Q
R
S
T
QT
interval
Widened QRS complex
and normal QT interval
Class 1c
Markedly depressed slope of depolarization

9. DIFFERENCES AMONG CLASS 1 ANTI-ARRHYTHMIC DRUGS
PROPERTY CLASS 1a CLASS 1b CLASS 1c
Na+ channel blockade Moderate Weak Powerful
Effect on K+ channels Block Open No effect
Action Potential
Action Potential Duration
(APD) &
Effective Refractory
Period(EFP)
Increases Decreases Normal
Na+ channel blockade -1c > 1a > 1b
Action Potential Duration &Effective Refractory Period-1a > 1c > 1b

10. Act on Contractile cardiac myocyte but not on Pace maker cells.
Reduce automaticity.
Inhibit arrhythmic myocardial excitation of higher frequency.
Prevent re-entry in Atrial and ventricular tissues
Do not alter the Resting Membrane Potential (Membrane stabilizers).
Exhibit use dependent block.
COMMON PROPERTIES OF CLASS 1 ANTI-ARRHYTHMIC DRUGS

11. QUINIDINE (1a)
• Isomer of quinine derived from Cinchona bark.
PHARMACOKINETICS:
 Absorbed orally
 short acting
 highly plasma protein bound
 undergoes glucuronidation
 high 1st pass metabolism
 Eliminated by kidneys
ATRIAL FLUTTER ATRIAL FIBRILLATIONS
VENTRICULAR FIBRILLATIONS
CARDIAC USES
EXTRA-CARDIAC USES
• Exhibits anti-malarial, anticholinergic, α- blocking, uterine stimulant and
antipyretic properties.

12. QUINIDINE (1a) Cont….d
Torsade's de pointes
Thrombocytopenia
Hypotension
Cinchonism
Diarrhea(GI upset)
DRUG INTERACTIONS:
• Reduces Digoxin clearance.
• Enzyme inhibitor, inhibits
CYP2D6, drug like Warfarin,
Codeine.
• Induced by Phenytoin,
Phenobarbitone
• Plasma quinidine concentration is
increased by Cimetidine and
Verapamil
TH,C
D
DEVIL PC
ADVERSE EFFECTS:

13. PROCAINAMIDE (1a)
• Analogue of Procaine
PHARMACOKINETICS:
 Administered by IV route or oral.
Metabolized by Acetylation,
Metabolite is N-acetyl procainamide,
Metabolism shows genetic variations.
 Eliminated by kidneys
• Administered as a loading dose of
10mg/kg at a rate of 20mg/min
followed by maintenance dose of
2mg/min.
• Hypotension
• Torsade’s de pointes
• SLE
• Bone marrow depression
Acute Supra
ventricular and
Ventricular
tachyarrhythmia
s
CLINICAL USES:
ADVERSE EFFECTS:

14. DISOPYRAMIDE (1a)
PHARMACOKINETICS:
 Absorbed orally.
 Shows plasma concentration
dependent plasma protein
binding.
 Metabolized in liver.
 Eliminated by kidneys.
• Also possess anticholinergic activity
• Useful in reducing muscle mass
• HOCM
ADVERSE EFFECTS:
• Torsade’s de pointes
• Anti cholinergic side effects
AT
Cardiac uses-
Extra cardiac uses-

15. LIGNOCAINE (1b)
• Local anesthetic with anti arrhythmic property.
• Selectively acts on diseased or ischemic myocardium.
PHARMACOKINETICS:
 Has a rapid onset but short
duration of action.
 IV route is preferred.
 Metabolized in liver.
DRUG OF
CHOICE
Ventricular
Tachycardia
Ventricular
Fibrillations
Digoxin induced
arrhythmias
Anesthesia induced
arrhythmias
Arrhythmias in
ICU
AMI induced
arrhythmias
ADVERSE EFFECTS:
 Nystagmus.
 Drowsiness.
 Dysarthria
 Tremors
 Muscle twitching
 Convulsions
CLINICAL USES:

16. PHENYTOIN (1b)
• Anti epileptic with anti arrhythmic property.
• Used as alternative to Lignocaine.
• Was used previously as drug of choice for digoxin induced arrhythmias.
ADVERSE EFFECTS:
• Potent enzyme inducer.
• Follows zero-order kinetics at therapeutic concentration.
Ataxia Nystagmus Mental confusion Hypotension
PHARMACOKINETICS:

17. MEXILETINE(1b)
• Analogue of Lignocaine.
TOCAINIDE (1b)
• Analogue of Lignocaine.
• Adverse effects include nausea, vomiting, hypotension and neurological
such as ataxia, tremors, dizziness, blurred vision. These can be minimized
by taking the drug with food
• Mainly useful in post-MI Ventricular arrhythmias. Other use is phantom limb
• Adverse effects include bone marrow depression and pulmonary fibrosis.
This drug is not used presently.
• Used in Ventricular arrhythmias.
Mexiletine or Tocainide can be used in combination with Quinidine or Sotalol to
increase efficacy and reduce toxicity of individual agent.

18. PROPAFENONE (1c)
• Possess mild β- blocking and calcium channel blocking properties.
PHARMACOKINETICS:
 Well absorbed orally.
 Metabolism generates 2 metabolites.1)5-hydroxy propafenone(CYP2D6 mediated)
2)N-desalkyl propafenone(weak Na+, β-blocker)
 Eliminated by liver and kidney.
• Supra ventricular arrhythmias.
• Ventricular arrhythmias.
• Refractory arrhythmias.
CLINICAL USES:

19. PROPAFENONE (1c) Cont….d
ADVERSE EFFECTS:
• Cardiac heart failure.
• Sinus bradycardia and
bronchospasm(β- blocking
action) .
DRUG INTERACTIONS:
• Quinidine and Fluoxetine inhibit CYP2D6
mediated metabolism of propafenone in
fast metabolizers.
• Dose should be Hepatic disease .
MORICIZINE (1c)
• Phenothiazine analogue.
• Useful for chronic treatment of ventricular arrhythmias.
• Contra-indicated in patients immediately after MI.
• Not preferred currently.

20. FLECAINIDE (1c)
• Analogue of Procainamide.
• Used for re-entrant atrio-ventricular tachycardia(Nodal tachycardia, WPW
Syndrome) or any tachycardia due accessory/aberrant pathways from atria/ventricle.
• Adverse effects: nausea, abdominal discomfort, blurred vision, tremors,
dizziness.
• Contra-indications: Cardiac failure, Sick sinus syndrome and in patients with past
history of MI or recovering MI.
ENCAINIDE (1c)
• It is no more used.