S7: interpreting ECGs, cardiac arrhythmias & CVS drugs

Question 1

Explain how arrhythmias can arise

Answer 1

Arrhythmia = abnormal heart rate or rhythm 
Tachycardia = ectopic pacemaker activity, afterdepolarisations, atrial flutter/atrial fibrillation, re-entry loop
Bradycardia = sinus bradycardia, conduction block

Question 2

Describe the re-entrant mechanism for generating arrhythmias

Answer 2

Block of conduction through damaged area region
Circus of excitation = excitation can take a long route to spread the wrong way through the damaged area
Possible to get several small re-entry loops in the atria -> atrial fibrillation

Question 3

List the 4 basic classes of anti-arrhythmic drugs

Answer 3

1) Drugs that block voltage-sensitive sodium channels
2) Antagonists of B-adrenoreceptors
3) Drugs that block potassium channels
4) Drugs that block calcium channels

Question 4

Describe the mechanism of action of class I drugs and their therapeutic use

Answer 4

Only blocks voltage gated Na+ channels in open or inactive state -> preferentially blocks damaged depolarised tissue
Little effect in normal cardiac tissue as it dissociates rapidly
Blocks during depolarisation but dissociates in time for next AP
Eg. lidocaine = slows upstroke, shortens AP, slows conduction velocity (used to be used following MI)

Question 5

Describe the mechanism of action of class II drugs and their therapeutic use

Answer 5

Blocks sympathetic action
Decrease slope of pacemaker potential in SA and slows conduction at AV node
Can prevent supraventricular tachycardia, used following MI, reduces O2 demand

Question 6

Describe the mechanism of action of class III drugs and their therapeutic use

Answer 6

Prolong the action potential by blocking K+ channels
Lengthens the absolute refractory period (can be pro-arrhythmic by prolonging QT interval)
Not generally used, except AMIODARONE (has other actions in addition to blocking K+ channels) which is used to treat tachycardia associated with Wolff-Parkinson-White syndrome

Question 7

Describe the mechanism of action of class IV drugs and their therapeutic use

Answer 7

Decreases slope of action potential at SA node, decreases AV nodal conduction, slows conduction & decreases force of contraction
Non-dihydropyridine types eg. verapamil (others act on vascular smooth muscle)

Question 8

Describe the mechanism of action of adenosine and its therapeutic use

Answer 8

Can be administered IV
Acts on A1 receptors at AV node
Enhances K+ conductance -> hyperpolarised cells of conducting tissue
Anti-arrhythmic

Question 9

Define the term ‘inotropic’ drug and the circumstances under which these drugs can be used

Answer 9

Positive inotropes = increase contractility and thus cardiac output
Cardiac glycosides (digoxin) = improves symptoms of heart failure but not long term outcome
B-adrenergic agonists (dobutamine) = cardiogenic shock, acute but reversible heart failure

Question 10

Explain the action of cardiac glycosides

Answer 10

Ca2+ is extruded via Na+/Ca2+ exchanger
Cardiac glycosides block Na+/K+ ATPase
Leads to rise in intracellular Na+ -> decrease in activity of Na+/Ca2+
Increase in intracellular Ca2+ -> more stored in SR
Increased force of contraction
Also cause increased vagal activity

Question 11

Describe how drugs can be used in the treatment of hypertension

Answer 11

Diuretics

ACE-inhibitors = inhibits the action of ACE which will reduce BP

Question 12

Explain the mechanism by which organic nitrates alleviate angina

Answer 12

Reaction of organic nitrates with thiols in VSM causes NO2- to be released
Nitric oxide is released endogenously from endothelial cells
NO activates guanylate cyclase
Increases cGMP
Lowers intracellular Ca2+ -> relaxation of VSM
Primary action: venodilation lowers preload, secondary action: coronary collateral arteries improve O2 delivery to the ischaemic myocardium

Question 13

Name some cardiovascular conditions which have an increased risk of thrombus formation and describe the pharmacological agents used to minimise this risk

Answer 13

Conditions: atrial fibrillation, acute myocardial infarction, mechanical prosthetic heart valves 
Anticoagulants = prevention of venous thromboembolism & DVT or atrial fibrillation
Eg. IV heparin, fractionated heparin, warfarin 
Antiplatelet drugs = prevention of platelet-rich arterial thrombus formation & following acute MI/high risk of MI
Eg. aspirin, clopidogrel

Question 14

Describe calcium channel blockers (dihydropyridine types)

Answer 14

Not effective in preventing arrhythmias but do act on vascular smooth muscle
Decrease peripheral resistance, decrease arterial BP -> decrease afterload
Useful in hypertension & angina
Eg. Amlodipine & nicardipine