15b – CV Arrhythmias

Question 1

Types of arrhythmias

Answer 1

• Tachycardia*
• Bradycardia
• Fibrillation*
• Conduction abnormalities
• *where most of our drugs target and treat

Question 2

Tachycardia

Answer 2

• HR too high
• *normal in physical activity but problem if too far

Question 3

Bradycardia

Answer 3

• HR too low
• *normal in sleep
• Could do a pacemaker in our animals, but tend not too

Question 4

Fibrillation

Answer 4

• Uncoordinated, rapid excitation/contraction

Question 5

Review of cardiac electrophysiology

Answer 5

• P wave: atrium depolarizes (SA node fastest)
• QRS complex: ventricular depolarizes
• T wave: repolarization of ventricle

Question 6

Phases of electrophysiology: ventricle depolarization

Answer 6

Phase 0: rapid depolarization, large Na influx and tapers with time
Phase 1: Na Ca exchange
*Phase 2: PLATEAU phase: pausing in depolarized stated (VG Ca channels open=Ca INFLUX!)
Phase 3: K channels open (slower): K efflux begins=brings down membrane potential
Phase 4: resting membrane potential

Question 7

Phase 4 in pacemakers

Answer 7

• Funny current: mix of Na and Ca channels that SLOWLY LEAK and cause a slow spontaneous depolarization until threshold=AP!

Question 8

Supraventricular tachycardia (problem in pacemakers)

Answer 8

• *increased automaticity if
  o Slope of phase 4 increased
  o Lower threshold potential (TP is more NEGATIVE)
  o Maximum diastolic potential (MDP) is more positive

Question 9

Premature ventricular contraction

Answer 9

• *ventricular tachycardia
• Early or late afterdepolarization
  o From abnormal Ca influx into cardiac cells DURING or immediately AFTER phase 3 of ventricular AP
• *another QRS before the next P-wave could happen
  o Absence of P waves!
  o INDEPENDENT of atrial depolarization

Question 10

Damage to Purkinje system (unidirectional conduction block)

Answer 10

• Ischemic or congenital damage to branches
• *no spread on damaged side so (no ‘forward excitation’)
  o Gets excited from the non-damaged side
• SELF-EXCITATION LOOP (‘backward excitation’)
  o INDEPENDENT of pacemaker inputs
• *most common cause of ventricular tachycardias

Question 11

Anti-arrhythmic drugs

Answer 11

• Grouped based on where they act
• *major effect (ignore the other effects)
• SIDE EFFECT: fatal cardiac arrhythmias

Question 12

Class I: effects

Answer 12

• *Na-channel inhibitor
• Decrease Na current=prolongs QRS phase
  o Reduces HR and cardiomyocyte excitability
• *do NOT want to block all of THEM

Question 13

What are Class I anti-arrhythmic drugs used for?

Answer 13

• Ventricular arrhythmias
  o Particularly tachycardias
  o Some in supraventricular arrhythmias

Question 14

Class Ia: targets and effects

Answer 14

• All cardiac cells
  o Including ventricular myocytes
• *decrease maximum of AP=longer depolarization=wider QRS
• Longer QT interval
  o Repolarization is NOT effect
  o Due to extra QRS time

Question 15

Class Ib: targets and effects

Answer 15

• Damaged ventricular myocytes
  o Usually problems with repolarization
• Doesn’t effect much as there should be lots of HEALTHY cells still
• Only effecting phase 0 in damaged cells
• QRS is similar

Question 16

Class Ic: targets and effects

Answer 16

• All cardiac cells, some preference for conduction cells
• Profound effect on phase 0=slows rate of depolarization
  o Slows spread of excitation=WIDEN QRS
  o Slightly longer QT interval

Question 17

Class Ia: drug examples

Answer 17

• *Quinidine
• Procainamide
  o not used much in dogs (hard for them to activate it)

Question 18

Use Quinidine to

Answer 18

• slow down HR, but may suppress cardiac contractility
• good to use for supra and ventricular arrhythmias
• *VERY FLEXIBLE DRUG
• Beware of side effects

Question 19

Class Ib: drug example

Answer 19

• Lidocaine

Question 20

Class II: main effect

Answer 20

• *beta-1 adrenergic receptor antagonist
  o Decrease cAMP=decreased contractility and HR
• Negative chronotrope, dromotrope and inotrope

Question 21

Class II: drug examples

Answer 21

• Metoprolol
• Atenolol

Question 22

What are Class II anti-arrhythmic drugs used for?

Answer 22

• Supraventricular tachycardias
  o Particularly where excessive sympathetic stimulation is the cause

Question 23

Class III: main effect

Answer 23

• *K-channel inhibitor
  o Prolonged refractory period (slow down repolarization)
• DELAYS time until opening, but then all open and rapidly repolarization like normal
  o Prolongs plateau phase
  o Reduces HR
• QRS is NOT affected
• Prolonged QT interval
• *relatively safe!

Question 24

Class III: other effects (not a strong)

Answer 24

• Block beta1 adrenergic receptors
• Block Na channels

Question 25

Class III: drug examples

Answer 25

• Amiodarone
• Bretylium
• Sotalol

Question 26

What are Class III anti-arrhythmic drugs used for?

Answer 26

• Refractory ventricular tachycardias
  o Especially those arising from re-entry

Question 27

Amiodarone

Answer 27

• Complex with lots of iodine’s
  o Can accumulate=’silver/purple cast’ to the skin
• *takes a long time to reach steady state

Question 28

Class IV: main effect

Answer 28

• Ca-channel inhibitor
• *more of an effect in pacemakers
  o Decreases contractility and HR
  o Vasodilation
• *don’t want it to have an effect in cardiomyocytes
  o it would DECREASE CONTRACTILITY
• Ca channels involved in the funny current are inhibited=takes longer for it to generate enough depolarization

Question 29

What are Class IV anti-arrhythmic drugs used for?

Answer 29

• Supraventricular tachycardias
• *good choice in hypertrophic cardiomyopathy

Question 30

Class IV: drug examples and when do you NOT use them?

Answer 30

• Verapamil
• Diltiazem
• **DO NOT USE IN DILATED CARDIOMYOPATHY (could decrease contractility too much)
• Can use in hypertrophic cardiomyopathy

Question 31

Class II and IV effects on SA node end up looking similar (pacemaker AP=no plateau phase)

Answer 31

• Phase 4 (funny current: spontaneous depolarization)
  o *slower rate of depolarization (longer to reach threshold=SLOWS HR
  o LONGER PR INTERVAL (p-wave may look similar)
• May have a stronger repolarization
• *longer PP interval (more so the ‘TP interval’)
• **relatively SAFE