Antiarrhythmics

How is cardiac muscle different to other types of muscle?

Relaxation must occur between contractions → exhibit tetany → contract and hold contraction for certain length of time

Where is the SA node located and what does it do?

Inferior to the superior vena cava

Pacemaker of the heart → sets sinus rhythm (60-80bpm)

Where is the AV node located and what does it do?

Inferior to the pulmonary trunk

Gives time for atria to contract so the ventricles can fill

What is the order of conduction in the heart?

1. SA node

2. AV node

3. Common bundle

4. Bundle (bundle of his)

5. Purkinje fibres → contraction from apex to base

What causes the P wave?

Atrial depolarisation

What causes the QRS complex?

Ventricular depolarisation

** atrial depolarisation is hidden

What causes the T wave?

Ventricular repolarisation

** repolarisation starts at the base

What forms the U wave on the ECG?

Delayed depolarisation from ventricles

What are the 2 subsets of tachyarrhythmias?

Supraventricular (involve atria or AV node)

Ventricular

what is Wolff-Parkinson-white syndrome?

Current goes down an accessory pathway (bundle of kent) and cause extra contractions in the ventricles → can lead to re-entry circuits

** AVRT

How do contractile cells generate an action potential?

Phase O (upstroke/ deplorasitaion): voltage gated (fast( Na+ channels open: -70 → +20

Phase 1 (initial repolarisation): Fast Na+ channels close. K+ channels open → K+ moves out → 0mV

Phase 2 (plateau): K+ moves out and Ca2+ moves in

Phase 3 (final repolarisation): L-type Ca2+ channels close. Ca2+ is taken back to SR by sodium-calcium exchanger and calcium proton ATPase pumps. Slow K+ channels open and K+ exits the cell

What are the different classes of antiarrhythmics?

• Class I: Na channel blocker

• Class II: beta blocker

• Class III: k channel blocker

• Class IV: Ca channel blocker

Name the sodium channel blockers

1a: Quinidine, Procainamide
1b: Lidocaine
1c: Flecainide

Ic > Ia > Ib

Name some beta blockers

Propranolol, Bisoprolol, Metoprolol

** class II

Name some potassium channel blockers

Amiodarone, Sotalol (also beta blcoker)

** class III

Name some calcium channel blockers

Verapamil, Diltiazem

** class IV

How do sodium channel blockers work?

Blocks Sodium Channels – affects the Rapid Depolarisation (Phase 0) →slowing of conduction within the cardiac muscle

Ia agents are midway, but also prolongs repolarisation (quinidine, procainamide)

Ib agents associate and dissociate rapidly (lidocaine) → binds in Phase 0 but dissociates in time for the next action potential

Ic agents associate and dissociate much more slowly (flecainide)

ECG effects of class Ia Na+ blockers and their side effects

** oral/ IV

↑ QRS, ± PR, ↑QT

side effects:

• Hypotension, reduced cardiac output

• GI symptoms

** pro-arythmic drugs → Torsades de pointes

ECG effects of class Ib Na+ blockers and their side effects

** oral/ IV

↑ QRS

Side effects:

• Dizziness

• Drowsiness

• GI upset

ECG effects of class Ic Na+ blockers and their side effects

** oral/ IV

↑ QRS, ↑ PR, ↑ QT

side effects:

• Proarrhythmic → sudden death especially with chronic use and in structural heart disease

• GI symptoms

When do you use each Na+ channel blocker?

Ia: not used often

• Quinidine: AF/Flutter, Brugada Syndrome

• Procainamide: supraventricular and ventricular tachycardias

Ib: Acute Ventricular Tachycardias

Ic:

• AF & Flutter

• Premature Ventricular contractions

• Wolff-Parkinson-White Syndrome

ECG effects of beta blockers and side effects

↑ PR, ↓ Heart Rate

Side effects:

• bronchospasm

• hypotension

• don’t use in partial AV block or acute heart failure (are used in stable heart failure)
  

When do you use beta blockers?

• Sinus and Catecholamine dependent tachycardia

• Re-entrant arrhythmias at AVN

• Protecting Ventricles from High Atrial Rates

How do beta blockers work?

Work by activating adenylyl cyclase→ produces cAMP → causes phosphorylation of Protein Kinase A (PKA) → acts on multiple downstream targets to produce r esponses

→ Positive Inotropy (predominantly in ventricular myocytes)

→ Positive Chronotropy (predominantly at SAN)

** block the effects of sympathetic activity on the SAN and AVN

How do potassium channel blockers work?

They prolong the plateau phase & repolarisation due to K+ channel blockade

Leads to:

• ↑ Action Potential Duration (APD)

• ↑ Refractory period

ECG effects of potassium channel blockers and side effects

Amiodarone (PO/ IV):

• ↑ QRS, ↑ PR, ↑ QT, ↓ Heart Rate

• Side effects: Pulmonary Fibrosis, Liver Disease, Thyroid Disease, Photosensitivity, Optic Neuritis

Sotolol (PO):

• ↑ QT, ↓ Heart Rate

• Side effects: Proarrhythmia, Fatigue, Insomnia

** solotol is also a beta blocker antagonist but has more of an effect on k+ channels

What happens in nodal cells?

1. Phase 4(diastole): funny Na+ channels open + T type Ca2+ channels open → reaches threshold (-40mV)

2. Phase 0 (upstroke): L-type Ca2+ channels open → +10mV → Ions move to contractile cells via gap junctions

3. Phase 3 (final repolarisation): L-type Ca2+ channels inactivate. K

4. + channels activate and K+ leaves the cell → cell depolarises

Difference between rate control and rhythm control drugs

Rate: increased heart rate due to increased automaticity of the AV node → Class II + Class IV + class V

** Adenosine, Beta blocker, Calcium channel blocker, Digoxin (ABCD)

Rhythm: due to increased automaticity within the contractile cells (atria/ventricles) → Class I + Class III

Why should class Ic not be given to people with ischaemic or structural heart conditions?

Can be pro arrhythmic for those patients

Ischaemic/sacr tissue conduct in a different way

How do you treat tosades’s the pointes

Magnesium sulphate → decreases QT

ECG effects of calcium channel blockers and side effects

↑ PR, ↑↓ Heart Rate

Side effects:

• Asystole in presence of β-blocker

• Caution in hypotension and reduced cardiac output

• GI upset (constipation)

How do calcium channel blockers work?

Results in delayed depolarisation of SAN

Reduction in conduction velocity (and slight increase to refractory period)

When do you use calcium channel blockers?

Supraventricular tachycardia

When do you use potassium channel blockers?

Most Arrhythmias including supraventricular & ventricular tachycardias

How does adenosine work?

Nucleoside binds to A1 receptors and activates K+ channels in SAN and AVN

→ leads to hyperpolarisation → reduced HR

→ refractory period increase due to decreased calcium activity

→ Slows AV conduction

** given IV

When would you use adenosine?

Convert re-entrant supraventricular arrhythmias

Coronary Artery Disease investigations

How do Cardiac Glycosides (Digoxin) work?

Inhibits 3Na+/2K+ ATPase

Enhances Vagal activity & causes direct AVN block

Slows AV conduction and slows heart rate

Side effects if digoxin?

Confusion, dizziness

GI Upset

Blurred Vision

Photosensitity

Skins Rashes

Arrhythymia (palpitations)

When would you use digoxin?

Reduce Ventricular rates in AF/Flutter

How does Ivabridine work?

Blocks funny ion current highly expressed in sinus node

Slows impulse generation at SA Node

** given orally

Side effects of Ivabridine

Flashing Lights

Teratogenicity → avoid in Pregnancy

When would you use Ivabridine?

↓ Heart Rate in HFrEF / Ischaemic heart disease

** has no effect on bp/ contractility

How does atropine work and when can we use it?

Selective muscarinic antagonist → blocks vagal activity to speed AV conduction and increase heart rate

Vagal Bradycardias