Anti-arrhythmic Drugs Flashcards
Define arrhythmia.
Abnormality in:
- HR.
- Regularity of HR.
- Site of impulse origin.
- Sequence of activation.
– disruption of conduction e.g. AV block.
What is phase 0 of nodal action potential caused by?
Influx of Ca2+ ions.
What do calcium channel blockers do?
Decrease phase 0 in nodal tissue.
- used to slow conduction through the AV node.
- useful for arrhythmias originating ABOVE the AV node.
- Which location in the heart is generally the pacemaker and why?
- Normal SA node rate of firing.
- Normal AV node rate of firing.
- Normal Bundle of His rate of firing.
- Normal Purkinje fibres rate of firing.
- SA node. It is the area that usually depolarises fastest.
- 80-120.
- 60-70.
- 40-50.
- 30-40.
- What is happening during phase 0 of myocardial cell action potential.
- Difference between atrial and ventricular myocardial cell AP.
- Fast sodium channels opening and depolarising the cell.
- Atrial much skinnier than ventricular.
What do sodium channel blockers do?
Work on myocardial tissue:
- ventricular – class 1b e.g. lidocaine.
- atrial and ventricular.
– class 1a e.g. procainamide.
– class 1c e.g. flecainide.
Causes of arrhythmia.
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.
Mechanisms of arrhythmia.
Abnormal automaticity.
Triggered activity.
Re-entry.
- Define automaticity.
- So what is abnormal automaticity.
- Spontaneous rhythmic depolarisation.
Normal function of conduction system. - Spontaneous rhythmic depolarisation in cells outside conduction system.
- diseased myocardial cells may develop abnormal automaticity.
Triggered activity.
After depolarisations.
Oscillations during repolarisation.
Can trigger subsequent APs.
Re-entry.
Abnormal circuit allows the impulse to self-perpetuate.
First thing to do when arrhythmia identified.
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.
Rule when giving anti-arrhythmic drugs.
Use only for haemodynamically significant arrhythmias.
Because anti-arrhythmic drugs can be pro-arrhythmic.
Treat the patient, not the ECG.
Define supraventricular arrhythmias.
Originate in SA node, atrial myocardium or AV node.
P waves present (but might be hard to see).
QRS complexes usually look normal.
Define ventricular arrhythmias.
Originate in the His-Purkinje system or ventricular myocardium.
No P waves present.
QRS complexes wide and bizarre.
- Vaughan Williams classification.
- Name drug used as anti-arrhythmic that does not fall w/in the classification.
- I = Na+ channel blockers.
II = beta blockers.
III = K+ channel blockers.
IV = Ca2+ channel blockers.
No Body Kills Cats. - Digoxin.
- Class Ia drugs used in vet med.
- Class Ib drugs used in vet med.
- Class Ic drugs.
- Quinidine (PO horses).
Procainamide. - Lidocaine (IV).
Mexiletine (PO). - Flecainide.
Propafenone.
- Class II drugs used in vet med.
- Class II drugs not used in vet med.
- Class III drugs used in vet med.
- Class IV drugs used in vet med.
– class IV not used in vet med. - 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?
- Atenolol (B1 receptor antagonist) (PO).
Esmolol (B1 receptor antagonist) (IV). - Propanolol.
- Sotalol (also a beta blocker), Amiodarone (has effects of all classes) (high risk of anaphylaxis IV).
- Diltiazem.
– Verapamil, (amlodipine - works in vasculature rather than the heart). - Ia, Ic, II, III.
– Ib.
– IV.
Class Ia drugs.
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.
Class Ib drugs.
Lidocaine.
- Life-threatening V arrhythmias.
- Selective for:
– diseased tissue.
– partially depolarised cells.
– cells w/ longer AP duration.
- Lidocaine dosing.
- Lidocaine side effects.
- 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.
- 2mg/kg IV bolus (effect in 2 mins, 10-20mins duration of effect for dogs.
- Nausea, depression, seizures, liver dysfunction.
Class Ic drugs.
Most potent Na+ blockers.
Not commonly used as risk of cardiac arrest.
Beta blockers.
- Activity.
- Considerations.
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.
Beta blocker drugs (class II).
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.
Class III drugs.
- Action.
- Example.
– other activities.
– pharmacology.
- Example 2.
– other actions.
– pharmacology.
– monitoring?
- 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.
Class IV drugs.
- actions.
- drug example.
– pharmacology.
– actions.
– combination w/ what for rate control.
- drug example 2.
– action.
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.
Digoxin.
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.
Digoxin pharmacology.
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.
Treatment for supraventricular tachyarrhythmia in emergency
Diltiazem IV.
Procainamide IV.
Esmolol IV (Care if cardiac dysfunction).
Amiodarone IV.
- SV arrhythmia treatment when no cardiac dysfunction.
- Tx of SV arrhythmias associated w/ cardiac disease and AF.
- A-B-C-D.
- Sotalol PO.
Atenolol PO. - Diltiazem PO.
Digoxin PO. - A fib - give beta blockers, Ca2+ blockers and/or Digoxin.
- Emergency Tx of V tachyarrhythmias.
- V tachyarrhythmia Tx w/o cardiac dysfunction.
- Tx of V tachyarrhythmias associated w/ cardiac disease.
- Lidocaine IV.
Procainamide IV.
Esmolol IV (care if cardiac dysfunction).
Amiodarone IV. - Atenolol PO.
- Sotalol PO.
Amiodarone PO.
