CVS 14 - Arrhythmias + Anti-Arrhythmic Drugs

Question 1

What are the 4 causes of tachycardias?

What are the 2 causes of bradycardia?

Answer 1

Tachycardia:

1) Ectopic pacemaker activity
2) Afterdepolarisations (abnormal DP’s following AP’s)
3) Atrial flutter/fibrillation
4) Re-entry loops

Bradycardia:

1) Sinus bradycardia - e.g.: sick sinus syndrome or drugs
2) Conduction block - problems at AV node

Question 2

What are early + delayed after-depolarisations (EAD’s + DAD’s)?

Answer 2

• EAD’s are abnormal depolarisations in phase 2 or 3 of the myocyte AP. More likely to occur if AP’s are prolonged (e.g.: by drugs) as there’s longer time for Ca2+ channels to recover.
• DAD’s are abnormal depolarisations during phase 4 of the myocyte AP, usually due to elevated IC Ca2+ levels.

Question 3

What are re-entry loops?

Answer 3

• A block of conduction in a damaged area means the excitation does not take the normal route, instead taken an alternative pathway looping back on itself, setting up a circus of excitation.
• You can get multiple re-entry loops in the atria leading to Afib.

Question 4

Give an example of a class 1 anti-arrythmic agent + explain how it works/what its effects on the AP is.
When is this agent used?

Answer 4

• Lidocaine (1b), use-dependent block of Na+ channels, only in open or inactivate state so preferentially blocks depolarised tissue. Blocks during DP but dissociates in time for next AP.
• Slows upstroke, shortens RP/AP, slows conduction velocity.
• Used to be used following MI, preventing automatic firing of DP’d damaged ventricular tissue.

Question 5

Give an example of a class 2 anti-arrhythmic agent + explain how it works.
What is this agent used for?

Answer 5

• Propranolol or atenolol.
• Blocks B1-Adr’s in the heart, to decrease the slope of pacemaker potential in SAN cells + slows conduction at AVN.
• Can prevent supraventricular tachycardia, used following MI (as MI causes increased SNS activity) + reduces O2 demand (reducing myocardial ischaemia).

Question 6

How do class 3 anti-arrhythmic agents work? 
Why are they generally not used in practice?
What is the one exception + what is it used for?

Answer 6

• Prolong the AP by blocking K+ channels, lengthening the absolute refractory period.
• Because they are pro-arrhythmic by prolonging the QT interval which can cause Ca2+ channels to reactivate, leading to EAD’s.
• Amiodarone, used to treat tachycardia associated with WPW syndrome.

Question 7

How do class 4 anti-arrhythmic agents work? (give examples)

Answer 7

• Verapamil, diltiazem
• Ca2+ channel blockers
• Decreases the slope of the upstroke/AP at the SAN, decreases AV nodal conduction + decreases force of contraction (negative inotropy).

Question 8

How does adenosine work as an anti-arrhythmic?

What is it used to treat?

Answer 8

• Acts on A1-adr’s at AV node, increases K+ conductance to hyperpolarise cells.
• Useful for terminating re-entrant SVT.

Question 9

How do ACE inhibitors treat hypertension + heart failure? (give an example)

Answer 9

• Perindopril
• Inhibits ACE to prevent to conversion of Agl into Agll, thus preventing vasoconstriction, production of aldosterone + Na+ reabsorption. Decreases circulating volume to reduce BP.
• Also decreases vasomotor tone to reduce afterload, and reduce blood volume to reduce preload which both work to reduce the workload of the heart in HF.

Question 10

When might ARB’s be used instead of ACE inhibitors?

Answer 10

• ACE inhibitors can result in excess bradykinin which results in a dry cough
• Use ARB’s in those who cant tolerate ACE inhibitors (e.g.: losartan)

Question 11

What are diuretics used to treat?

Answer 11

• HF + Hypertension
• Loop diuretics useful in congestive HF, e.g.: furosemide by reducing pulmonary and peripheral oedema by decreasing Na+ retention.

Question 12

What are DHP Ca2+ channel blockers used to treat + how?

Answer 12

• DHP Ca2+ channels blockers not effective as anti-arrhythmics
• Act on vascular smooth muscle to reduce Ca2+ entry and induce relaxation of peripheral vessels
• Useful for hypertension, angina, coronary artery spasms - e.g.: Amlodipine + nifedipine

Question 13

How do cardiac glycosides work as a positive inotrope?

How do cardiac glycosides reduce HR?

Answer 13

• E.g.: Digoxin
• Blocks the Na/K ATPase, increasing IC Na+
• Decreases efflux of Ca2+ via NCX (decreased Na+ concentration gradient)
• Increased Ca2+ ions stored in SR leading to increased force of contraction.
• Also increase vagal activity, which slows AV conduction + decreases HR.

Question 14

What are B1-Adr agonists used to treat? (give an example)

Answer 14

• E.g.: dobutamine

- Stimulate receptors at SAN + AVN used in cardiogenic shock or acute + reversible heart failure.

Question 15

Why is it better to use ACE inhibitors or ARB’s to treat HF than cardiac glycosides?

Answer 15

• Cardiac glycosides only relieve symptoms by making heart contract harder, but this is not good long-term
• Better to reduce workload by using ACEi’s, ARB’s or even B-blockers.

Question 16

How are nitrates used in the treatment of angina? (give examples)

Answer 16

• Reaction of organic nitrates with thiols in vascular smooth muscle causes NO2 release. NO2 is reduced to NO.
• NO activates GC, increases cGMP, lowers IC Ca2+ and causes relaxation of vascular SM. Therefore how a powerful vasodilatory effect on veins.
• This lowers preload (to reduce work load of heart + lowers O2 demand) + improves O2 delivery to ischaemic myocardium
• GTN spray or isosorbide dinitrate (longer lasting).

Question 17

Which conditions carry an increased risk of thrombus formation?
What are the 2 main kinds of antithrombotic drugs?

Answer 17

• Atrial fibrillation, Acute MI + Mechanical prosthetic heart valves.
  1) Anticoagulants - prevent venous thromboembolism, e.g.: heparin which inhibits thrombin or warfarin which antagonises the action of vit K.
  2) Antiplatelets - prevents platelet rich arterial thrombus formation following acute MI - e.g.: aspirin.