Antiarrhythmic drugs

Question 1

What are the mechanisms of cardiac arrhythmias?

Answer 1

Result from disorders of impulse formation, conduction, or both

Causes of arrhythmias:

• Cardiac ischaemia
• Excessive discharge or sensitivity to autonomic transmitters
• Exposure to toxic substances
• Unknown etiology

Question 2

What are the classes of arrythmic mechanisms?

Answer 2

Automaticity:

• Enhanced
• Abnormal

Triggered activity:

• Early afterdepolarisation
• Delayed afterdepolarisation

Re-entry

Question 3

What are the principles of cardiac pharmacotherapy?

Answer 3

• Alter HR
• Increase force of cardiac muscle contraction
• Alter depolarisaton/repolarisation of the myocardium
• Alter blood flow through the coronary arteries

Question 4

Which drugs are used to alter HR?

What is their MoA?

Answer 4

• Beta blockers
  
  • Blocks B₁ receptors in the SA and AV nodes, blocking sympathetic input to reduce HR (reduces ventricular rate by blocking AV node)
• Atropine
  
  • Blocks Ach recceptors in SA and AV nodes, blocking parasympathetic input to increase HR

Question 5

Which drugs are used to increase the force of contraction of cardiac muscle?

Answer 5

• Cardiac glycoside (usually digoxin)

Question 6

How do cardiac glycosides (digoxin) increase force of contraction?

Answer 6

1. Inhibits Na⁺/K⁺ATPase pump, increasing intracellular Na⁺
2. Ca²⁺ exchanged passively for Na⁺ via Na⁺/K⁺ exchanger that relies on NA⁺ concentration gradient
3. = Increased cytoplasmic Ca²⁺ as less extruded
4. Increases vagal tone = reduced HR

Question 7

How do beta blockers reduce force of contraction as a side effect?

Answer 7

Block adrenergic receptors, blocking the effect of adrenaline.

Reduced iCa²⁺ therefore reduced force of contraction

Question 8

How do Ca²⁺ antagonists reduce force of contraction as a side effect?

Answer 8

Inhibit L-type Ca²⁺ channels, decreased iCa²⁺ , therefore reducing force of contraction

Question 9

Which drugs are used to alter depolarisation/repolarisation of the myocardium?

What are their classes?

Answer 9

Quinidine, Disopyramide: Class 1a

Lidocaine: Class 1b

Flecainide, Propafenone: Class 1c

Amiodarone, Dronedarone, Sotalol: Class III

Verapamil, Diltiazem : Class IV

Question 10

What is the mechanism of action of Lidocaine?

Answer 10

Lidocaine: Class 1b

Blocks Na+ channels in actively depolarising cells/ depolarised areas, shortening the action potential

Question 11

What is the mechanism of action of Quinidine?

Answer 11

Quinidine: Class 1a

Delay depolarisation by acting on fast Na+ channels

Question 12

What is the mechanim of action of amiodarone?

Answer 12

Class III

K⁺ channel blocker, delays repolarisation

Question 13

What is the mechanism of action of verapamil?

Answer 13

Verapamil: Class IV

Block L typeCa2+ channels

Shorten phase 0 and 2 of the cardiac action potential

Reduces iCa2+, therefore -ve inotropic effects on cardiomyocytes

Affect pacemaker cells- slow influx of Ca²⁺ (rate of discharge)-> reduce HR

Question 14

What is the mechanims of action of adenosine?

What is it used for?

Answer 14

Binds A₁ receptor in pacemaker tissue, inhibits adenylate cyclase, reduces cAMP; K⁺ efflux increases and cells are hyperpolarised.

Used IV to diagnose and treat AV node dependent tachycardias.

Question 15

Calcium channel blockers: describe the roles of non-dihydropyridines

Name 2 drugs from this class

Answer 15

Verapamil and diltiazem (class IV)

Work on the myocardium and arterioles:

• Anti-arrhythmic by AV node block
• Anti-angina
• Anti HTN by arteriolar relaxation