EP3 Anti-arrhythmic drugs

Question 1

What are the 3 main mechanisms for tachyarrhythmias?

Answer 1

-Abnormal automaticity
-Triggered activity
-Reentry

Question 2

Vaughn-Williams classification of AADs

Answer 2

-Groups most AADs into 4 classes based on their mechanism

Question 3

Describe the action of Class I AADs (Na channel blockers)

Answer 3

-Block Na channels in the open or inactivated state
-This decreases the rise of phase 0 depolarisation and slows conduction velocity
-Class I AADs divided into 1A,1B, 1C

Question 4

Action of Class 1A AADs (Na channel blockers)?

Answer 4

Class 1A drugs
-moderately depress phase 0 depolarisation by blocking fast Na channels
-prolong repolarisation by blocking K channels
-results in prolonged action potential and refractory period

Question 5

Examples and side effects of Class 1A AADs (Na channel blockers)?

Answer 5

-Procainamide
-Quinidine (blurred vision, headache, tinnitus)
-Disopyramide (anti-cholinergic effects: blurred vision, constipation, dry mouth)

Question 6

Uses of Class 1A AADs (Na channel blockers)?

Answer 6

-Treat VT
-Treat recurrent AF

Question 7

Action of Class 1B AADs (Na channel blockers)?

Answer 7

-Shorten repolarisation by blocking Na channels that activate during late phase 2 of the action potential
-shorten duration of action potential and refractory period

Question 8

Examples and side effects of Class 1B AADs (Na channel blockers)?

Answer 8

-Lidocaine (CNS toxicity: seizures)
-Mexiletine (nausea and vomiting)

Question 9

Uses of Class 1B AADs (Na channel blockers)?

Answer 9

-Treatment of Ventricular arrhythmias

Question 10

Action of Class 1C AADs (Na channel blockers)?

Answer 10

-Powerful fast Na channel blockers
-Significantly depress phase 0 depolarisation
-Inhibit His-Purkinje conduction system
-Have a limited effect on repolarisation and refractory period

Question 11

Examples and side effects of Class 1C AADs (Na channel blockers)?

Answer 11

-Flecainide
-Propafenone
(Dizziness, blurred vision, nausea)

Question 12

Uses of Class 1C drugs (Na channel blockers)

Answer 12

-Treatment of refractory ventricular arrhythmias

Question 13

What is a risk of all Class 1 AADs (Na channel blockers)?

Answer 13

-They can be pro-arrhythmogenic

Question 14

Action of Class 2 AADs (beta blockers)?

Answer 14

-Act on beta 1 receptors
-Prevent the action of catecholamines on the heart
-Depress sinus node automaticity and slow conduction through AV node which causes decreased heart rate and contractility

Question 15

Uses of Class 2 AADs (beta blockers)?

Answer 15

-Used to treat arrhythmias provoked by increased sympathetic activity

Question 16

Examples of Class 2 AADs (beta blockers)?

Answer 16

-Propranolol
-Metoprolol
-Atenolol
-Esmolol (given IV in emergencies due to fast onset and short half life)

Question 17

Action of Class 3 AADs (K channel blockers)?

Answer 17

-Block K channels that are responsible for phase 3 repolarisation
-This increases duration of action potential and refractory period

Question 18

Uses of Class 3 AADs (K channel blockers)?

Answer 18

-Used to treat supraventricular/ventriuclar tachyarrhythmias
-Also AF/atrial flutter

Question 19

Examples and side effects of Class 3 AADs (K channel blockers)?

Answer 19

-Amiodarone (pulmonary fibrosis, skin discolouration, neuropathy, hepatotoxicity, corneal micro-deposits, thyroid dysfunction)
-Dronedarone (less lipophilic, shorter half life, no iodine, not as effective as ami)
-Sotalol (Block B receptors)
-Dofetilide, Ibutilide (most selective K channel blockers, but pro-arrhythmogenic)

Question 20

Action of Amiodarone (K channel blocker)

Answer 20

-Blocks K, Na, Ca channels
-Blocks alpha and beta receptors
-But has long half life so can stay in tissue for months

Question 21

Action of Class 4 AADs (Ca channel blocker)

Answer 21

-Block voltage-sensitive Ca channels during depolarisation in SA and AV nodes
-This causes slower conduction and reduced contractility of heart

Question 22

Uses of Class 4 AADs (Ca channel blocker)?

Answer 22

-Used to treat SVT and AF

Question 23

Examples and side effects of Class 4 AADs (Ca channel blocker)?

Answer 23

-Nondihydropyridine calcium channel blockers (e.g. Verapamil, Diltiazem)

Question 24

Which AADs do not fit into classes?

Answer 24

-Digoxin
-Adenosine
-Magnesium sulphate

Question 25

Action of Digoxin

Answer 25

-Inhibits NA/K pump by binding to K binding site
-Causes increased intracellular Na
-Casues Na/Ca exchanger to pump Na out and Ca in
-Increased intracellular Ca causes increased myocardial contractility

-Also stimulates parasympathetic system, increases activity of Vagus nerve, slowing Sinus discharge rate and decreased AV conduction

Question 26

Uses of Digoxin

Answer 26

-Heart failure
-AF

Question 27

Action of Adenosine

Answer 27

-Stimulates A1 adenosine receptors found in atrium, SA, AV node
-Causes decreased automaticity and conduction velocity and prolonged refractory period

Question 28

Uses of Adenosine

Answer 28

-Short half life, given IV
-Treats acute SVT
-Non-toxic
-Side effects: chest pain, hypotension

Question 29

Action of Magnesium sulphate

Answer 29

-Transports Na, K, Ca across cell membranes
-Mechanism unknown

Question 30

Uses of Magnesium sulphate

Answer 30

-Treats Torsades de Pointes
and digoxin-induced arrhythmias