Anti-arrhythmic Drugs

Question 1

Define arrhythmia.

Answer 1

Abnormality in:
- HR.
- Regularity of HR.
- Site of impulse origin.
- Sequence of activation.
– disruption of conduction e.g. AV block.

Question 2

What is phase 0 of nodal action potential caused by?

Answer 2

Influx of Ca2+ ions.

Question 3

What do calcium channel blockers do?

Answer 3

Decrease phase 0 in nodal tissue.
- used to slow conduction through the AV node.
- useful for arrhythmias originating ABOVE the AV node.

Question 4

1. Which location in the heart is generally the pacemaker and why?
2. Normal SA node rate of firing.
3. Normal AV node rate of firing.
4. Normal Bundle of His rate of firing.
5. Normal Purkinje fibres rate of firing.

Answer 4

1. SA node. It is the area that usually depolarises fastest.
2. 80-120.
3. 60-70.
4. 40-50.
5. 30-40.

Question 5

1. What is happening during phase 0 of myocardial cell action potential.
2. Difference between atrial and ventricular myocardial cell AP.

Answer 5

1. Fast sodium channels opening and depolarising the cell.
2. Atrial much skinnier than ventricular.

Question 6

What do sodium channel blockers do?

Answer 6

Work on myocardial tissue:
- ventricular – class 1b e.g. lidocaine.
- atrial and ventricular.
– class 1a e.g. procainamide.
– class 1c e.g. flecainide.

Question 7

Causes of arrhythmia.

Answer 7

Structural remodelling.
- e.g. altered intracellular communication or extracellular matrix composition.
Electrical remodelling.
- e.g. altered ion channel function or intracellular calcium response.
Haemodynamics.
- e.g. sinus arrhythmia.
Endocrine.
- e.g. electrolyte disturbances.
Primary cardiac disease.
- structural remodelling.
– cardiomyopathies.
– MMVD.
Non-cardiac disease.
- Electrolyte disturbances due to metabolic disease.
– hyperkalaemia in blocked cats or Addison’s disease.
- Systemic disease (inflammation, neoplasia etc.)
– ectopic complexes in GDV or splenic neoplasia.

Question 8

Mechanisms of arrhythmia.

Answer 8

Abnormal automaticity.
Triggered activity.
Re-entry.

Question 9

1. Define automaticity.
2. So what is abnormal automaticity.

Answer 9

1. Spontaneous rhythmic depolarisation.
   Normal function of conduction system.
2. Spontaneous rhythmic depolarisation in cells outside conduction system.
   - diseased myocardial cells may develop abnormal automaticity.

Question 10

Triggered activity.

Answer 10

After depolarisations.
Oscillations during repolarisation.
Can trigger subsequent APs.

Question 11

Re-entry.

Answer 11

Abnormal circuit allows the impulse to self-perpetuate.

Question 12

First thing to do when arrhythmia identified.

Answer 12

Investigate for underlying disease and treat as appropriate.
- medical therapy for CHF.
- unblock a cat w/ urethral obstruction.
– hyperkalaemia.
- Sx for GDV.
– electrolyte abnormalities and cytokine release.

Question 13

Rule when giving anti-arrhythmic drugs.

Answer 13

Use only for haemodynamically significant arrhythmias.
Because anti-arrhythmic drugs can be pro-arrhythmic.
Treat the patient, not the ECG.

Question 14

Define supraventricular arrhythmias.

Answer 14

Originate in SA node, atrial myocardium or AV node.
P waves present (but might be hard to see).
QRS complexes usually look normal.

Question 15

Define ventricular arrhythmias.

Answer 15

Originate in the His-Purkinje system or ventricular myocardium.
No P waves present.
QRS complexes wide and bizarre.

Question 16

1. Vaughan Williams classification.
2. Name drug used as anti-arrhythmic that does not fall w/in the classification.

Answer 16

1. I = Na+ channel blockers.
   II = beta blockers.
   III = K+ channel blockers.
   IV = Ca2+ channel blockers.
   No Body Kills Cats.
2. Digoxin.

Question 17

1. Class Ia drugs used in vet med.
2. Class Ib drugs used in vet med.
3. Class Ic drugs.

Answer 17

1. Quinidine (PO horses).
   Procainamide.
2. Lidocaine (IV).
   Mexiletine (PO).
3. Flecainide.
   Propafenone.

Question 18

1. Class II drugs used in vet med.
2. Class II drugs not used in vet med.
3. Class III drugs used in vet med.
4. Class IV drugs used in vet med.
   – class IV not used in vet med.
5. What drug classes are used for both V and SV arrhythmias?
   – what classes are used for V arrhythmias only?
   – what classes are used for SV arrhythmias only?

Answer 18

1. Atenolol (B1 receptor antagonist) (PO).
   Esmolol (B1 receptor antagonist) (IV).
2. Propanolol.
3. Sotalol (also a beta blocker), Amiodarone (has effects of all classes) (high risk of anaphylaxis IV).
4. Diltiazem.
   – Verapamil, (amlodipine - works in vasculature rather than the heart).
5. Ia, Ic, II, III.
   – Ib.
   – IV.

Question 19

Class Ia drugs.

Answer 19

Quinidine.
- horses for cardioversion of atrial fibrillation.
- pro-arrhythmic, increases ventricular rate in atrial fibrillation, can become hypotensive.
Procainamide.
- SV and V arrhythmias (SA).
- Expensive.

Question 20

Class Ib drugs.

Answer 20

Lidocaine.
- Life-threatening V arrhythmias.
- Selective for:
– diseased tissue.
– partially depolarised cells.
– cells w/ longer AP duration.

Question 21

1. Lidocaine dosing.
2. Lidocaine side effects.

Answer 21

1. • 2mg/kg IV bolus (effect in 2 mins, 10-20mins duration of effect for dogs.
     – switch to CRI 20-50micrograms/kg/min IV.
     - 0.5-1mg/kg bolus in cats.
     – switch to CRI 10-25micrograms/kg IV.
     - 0.25-0.5mg/kg in large animals IV.
2. Nausea, depression, seizures, liver dysfunction.

Question 22

Class Ic drugs.

Answer 22

Most potent Na+ blockers.
Not commonly used as risk of cardiac arrest.

Question 23

Beta blockers.
- Activity.
- Considerations.

Answer 23

Reduce pacemaker current in phase 4.
- decrease rate of spontaneous depolarisation.
Slow sinus and AV node conduction.
Inhibit afterdepolarisations (trigger activity).
Reduce intracellular Ca2+ overload.
Reduce HR, negative inotropy.
- can make things worse for a patient in active heart failure.
Care if respiratory disease present.
- can cause bronchoconstriction if block B2 receptors.
Do not stop suddenly - wean dose.

Question 24

Beta blocker drugs (class II).

Answer 24

Atenolol (B1 blocker).
- PO, low dose, titrate up.
- Supraventricular and ventricular arrhythmias.
Esmolol (B1 blocker).
- IV (emergencies), CRI.
- Ultra-short acting.
- Supraventricular and ventricular arrhythmias.
Propranolol (B1 and B2 blocker).
- PO, rarely used.

Question 25

Class III drugs.
- Action.
- Example.
– other activities.
– pharmacology.
- Example 2.
– other actions.
– pharmacology.
– monitoring?

Answer 25

• Block K+ channels.
• Prolong refractory period and AP duration.
• Sotalol.
  – Also beta blocker.
  – SV and V arrhythmias.
  – PO –> BID, steady state 2-3d.
  – Do not stop suddenly (beta blocking activity).
• Amiodarone.
  – class I, III (II, IV) actions.
  – V and SV arrhythmias.
  – can result in reduced systolic function.
  – PO, long half life, loading doses then maintenance doses.
  – IV (allergic reactions) – Nexterone.
  – Side effects: GI, hepatotoxicity, thyroid.
  – monitor serum chemistry every 3m.

Question 26

Class IV drugs.
- actions.
- drug example.
– pharmacology.
– actions.
– combination w/ what for rate control.
- drug example 2.
– action.

Answer 26

Block Ca2+ channels.
Inhibit inward movement of Ca2+.
- slow phase 4.
- slow AVN conduction.
- decrease automaticity.
- reduce contractility.
- vasodilation (Amlodipine).
Diltiazem.
- PO (diff formulations), IV.
- Quick onset of action (PO).
- Slow AVN conduction.
– SV tachyarrhythmias (e.g. AF, atrial tachycardia etc.)
- Combination w/ digoxin for rate control (AF).
- Verapamil.
– second choice, more negative inotropic effect.

Question 27

Digoxin.

Answer 27

Parasympathomimetic.
- Decreases SA node firing.
- Slows AVN conduction.
AF.
- In combination w/ Diltiazem for rate control.
V small positive inotropic effect.
- Inhibits Na+/K+ATPase.
– uses sodium calcium exchanger to get rid of sodium another way.
– Increases intracellular Ca2+ (increases contractility).
–> Can be pro-arrhythmic – V arrhythmias.

Question 28

Digoxin pharmacology.

Answer 28

Low doses!
- 0.003-0.005 mg/kg BID PO, max o.25mg/dog.
3-5d until therapeutic levels.
Adverse effects = GI, arrhythmia.
Trough levels after 7d (6-8h post pill).
Low levels (0.5-1.0nmol/L): positive vagomimetic effect, reduced toxicity.

Question 29

Treatment for supraventricular tachyarrhythmia in emergency

Answer 29

Diltiazem IV.
Procainamide IV.
Esmolol IV (Care if cardiac dysfunction).
Amiodarone IV.

Question 30

1. SV arrhythmia treatment when no cardiac dysfunction.
2. Tx of SV arrhythmias associated w/ cardiac disease and AF.
3. A-B-C-D.

Answer 30

1. Sotalol PO.
   Atenolol PO.
2. Diltiazem PO.
   Digoxin PO.
3. A fib - give beta blockers, Ca2+ blockers and/or Digoxin.

Question 31

1. Emergency Tx of V tachyarrhythmias.
2. V tachyarrhythmia Tx w/o cardiac dysfunction.
3. Tx of V tachyarrhythmias associated w/ cardiac disease.

Answer 31

1. Lidocaine IV.
   Procainamide IV.
   Esmolol IV (care if cardiac dysfunction).
   Amiodarone IV.
2. Atenolol PO.
3. Sotalol PO.
   Amiodarone PO.