Anti-Arrhythmic Drugs

Question 1

Drugs which Induce Dysrhymias

Answer 1

Sympathomimetic Drugs: Increase automaticity

Digitalis
• Drugs prolonging QT time:
– Anti-dysrhythmic drugs
– Antihistamines
– Antipsychotics
– Cisapride, etc.( Torsades de pointes)

Question 2

Anti-Dysrhythmic drugs

Answer 2

Anti-dysrhythmic effects via
–  cardiac automaticity
–  in SA or AV node
• All have an effect on ion flux
across membranes.
– prolong AP
– effective refractory period

Question 3

Vaughan-Williams Classification of antidysrhythmic drugs

Answer 3

CLASS I : Na channel blockers

CLASS II : Beta blockers

CLASS III: K channel blockers

CLASS IV: Ca channel blockers

Other drugs digoxin, adenosine, etc.

Question 4

Class 1 Anti-dysrhythmic drugs

Answer 4

All block rapid sodium channels,
therefore prolong the refractory period
in myocardial tissue where the AP is
dependent on sodium flux, like atrial
myocytes, His-Purkinje system and
ventricular myocardium.
• So: effective for re-entry dysrhythmia

Question 5

What do different classes of drugs do?

Answer 5

CLASS IA: Open channels

CLASS IB: Inactive channels

CLASS IC: Open channels

Question 6

Class 1A

Answer 6

Quinidine
Procainamide
Disopyramide

Open channels
Dissociates slowly
Inhibits fast sodium
channels (intermediate
effect)
 Prolong APD by blocking
potassium efflux channels.
 Prolongs repolarization
 Delay conduction via atria,
AV node, bundle of His
 Prolong ventricular
refractory and QT interval

Question 7

Quinidine

Answer 7

Class 1A
Isomere of Quinine – cinchona bark
• Use declined due to side effects
• Indications:
– Supraventricular and ventricular dysrhythmias

Question 8

Quinidine: Side effects

Answer 8

• 30% - GIT: nausea, vomiting, diarrhoea
• Hypotension: Especially with IV: ? Alpha
antagonist
• Cinchonism: headache, tinnitus, visual
disturbances
• Hypersensitivity: thrombocytopenia
• Widening of QRS and QT prolongation
– Torsades de pointes
– “Quinidine syncope" :
– Sudden death (0.5 – 4%)

Question 9

Procainamide

Answer 9

Effect like quinidine
• SE:
– Lupus: reversible arthralgia and rash
• Indications:
– Less hypotension
– Oral/IV: supraventricular and ventricular
dysrhythmias
– Use generally less than before

Question 10

Disopyramide

Answer 10

1A
Oral for ventricular dysrhythmias
• Negative inotropic and antimuscarinic.
– Caution in heart failure and elderly

Question 11

Class 1B

Answer 11

Inhibit fast sodium channels
 WEAKEST SODIUM CHANNEL
BLOCKERS: little change in
QRS duration in normal cardiac
tissue and minimal effect on
repolarization.
 Shorten repolarization
 Shorten duration of AP and
refractory period
– Lidocaine = lignocaine

Question 12

Lidocaine

Answer 12

Only IV; Extensive first pass metabolism
• Therapeutic range: 2-6 ug/ml
• Metabolism dependent on liver blood flow:
Congestive heart failure, cardiogenic shock
leads to raised plasma levels
• Propranolol, verapamil, cimetidine may cause
increased levels
• Indication: Ventricular tachy-dysrhythmias

Question 13

SE of Lidocaine

Answer 13

CNS: ( > 5 ug/ml)
– Circum-oral paresthesia
– Tinnitus
– Slurred speech
– Confusion
– Drowsiness
– Convulsions, CNS suppression
• Delay conduction in in normal
cardiac tissue

Question 14

Mexiletine

Answer 14

Class 1B

Oral for sympotomatic ventricular dysrhytmias

Question 15

Class 1C

Answer 15

Flecainide, Propafenone
• More potent effect op fast
sodium channels
• Suppress Phase 0 of AP
• Delay depolarisation
significantly
• Delay conduction
• Minimal effect on
repolarisation

Question 16

Flecainide

Answer 16

Indications:
Supraventricular dysrhythmias and lifethreatening ventricular dysrhythmias
• SE:

Question 17

SE of Flecainide

Answer 17

– Increase mortality in patients after myocardial
infarction
– Bronchospasm
– Leukopenia, Thrombocytopenia
– Convulsions

Question 18

Class II: B-blockers

Types
MOA

Answer 18

No-selective: Propranolol, Sotalol and Timolol

Cardio-selective: Atenolol,Metoprolol and Esmolol

A and B-Blockers: Labetalol and Carvedilol

Question 19

Class II

Answer 19

Inhibit sympathetic
activity: therefore
• cardiac automaticity
and conduction
– ↓ heart rate
– ↓ AV conduction

Prevent shortening of refractory period
on all levels.
ischemia-dependent VF, exercise
induced dysrhythmias, prolonged QT
syndrome

Question 20

SE of B-blockers

Answer 20

Bronchospasm
• Heart failure
• Bradycardia; AV Block
• Peripheral arterial insufficiency in patients
with peripheral vascular disease or
Raynaud’s
• Depression
• Dreams
• Sexual Dysfunction

Question 21

Class III: K+ Channel Blockers

Answer 21

Suppress re-entry
dysrhythmias, except TdP, in
atria and ventricles. Especially
effective in AF, atrial flutter, and
monomorphic ventricular
tachycardia.
More pronounced prolongation
of AP @ slow heart rate:
“reversed use-dependent.

Question 22

Class III: K+ Blockers,Drugs

Answer 22

Amiodarone
• Ibutilide
• Dofetilide
• Sotalol

Question 23

Amiodarone

Answer 23

K channel blocker
• Na channel blocker: (Class 1a)
• Alfa & Beta – blocking activity
(non-competitive; weak)
• Calcium channel blocker
• Oral/ IV
• T½: 30-60 DAYS
• Indications: Supraventricular and
Ventricular dysrhythmias

Question 24

Amiodarone: SE

Answer 24

Causes dysrhythmias in 2%, but seldom
Torsades de pointes
– Hypotension, AV block, various other
dysrhythmias
• Severe pulmonary fibrosis – Fatal
• Blue discolouration of face (5%)
• Thyroid dysfunction (5%)
• Yellow/brown discolouration of eyes
• Hepatic dysfunction: may be irreversible
• Constipation (20%)

Question 25

Amiodarone-Drug Interactions

Answer 25

Inhibits CYP3A and P-glycoprotein.
• Digoxin, warfarin, anti-dysrhythmic
drugs, anticonvulsants, etc.

Question 26

Class IV: Calcium Channel Blockers

Answer 26

Non-dihydropyridine calcium channel
blockers:
Block L- type, high voltage- calcium channels
Verapamil and Diltiazem :
– SA & AV node
– Decrease SA Automaticity
– Decrease AV Node conduction velocity
– Slow down ventricular rate during AF

Question 27

Indications for Class IV drugs

Answer 27

For acute supra-ventricular tachydysrhythmias
• Heart rate control in AF.
– Lower both resting and exercise heart rate
(digoxin lowers heart rate during rest in AF).
• Also prevent VT or VF due to coronary
artery spasm.

Question 28

Other anti-dysrhythmic drugs

Answer 28

Digitalis: Atrial fibrillation and severe heart
failure
• Adenosine: Supraventricular tachycardia
• Magnesium: Ventricular and
supraventricular dysrhythmias
• Adrenaline: Cardiac arrest and fibrillation
• Atropine: bradycardia

Question 29

Adenosine

Answer 29

Drug of choice for acute PSVT
• t½ = 10 seconds.
• Mechanism of action:
• Activates adenosine (A1) receptors
– →Activates Ach-sensitive K channels and
blocks Ca influx
– →Suppresses SA and AV nodes, vasodilation
of coronary vessels
• Cell hyperpolarizes

Question 30

Adenosine and Pharmcological Cardioversion

Answer 30

AV node conduction is blocked completely for a
couple of seconds short asystole
 Terminates SVT by preventing retrograde
conduction of re-entry impulses via AV node.

Question 31

Side effects of Adenosine

Answer 31

Blushing (20%)
• Shortness of breath, bronchospasm
• Headache
• Hypotension
• Nausea
• Paresthesia
• CONTRA INDICATION : HEART
TRANSPLANT

Question 32

Digoxin

Answer 32

vagal tone, slows AV conduction and
prolongs AV node refractory period.
• Used in AF for rate control (β-blockers and
CCBs preferred: more rapid onset of
action and AV node blockade)
• Digoxin:
– < bradycardia than β-blockers,
– < cardiac contractility than verapamil.

Question 33

Magnesium Sulfate

Answer 33

Mg due to loop diuretics or pathology: 
dysrhythmias, CHF.
i.v.
INDICATIONS:
• HYPOMAGNESEMIA
• DIGOXIN TOXICITY
• TORSADES DE POINTES