Cardiac arrhythmia drugs Flashcards
What must happen in order for the heart to function effectively?
- Heart needs to contract sequentially (atria then ventricles) and synchronously
- Relaxation must occur between contractions
- Coordination of heartbeat is a result of a complex coordinated sequence of changes in membrane potentials and electrical discharges in various heart tissues
How does excitation spread throughout the heart normally?
- Sinoatrial node
- Passes through atria to AV node
- Passes through septum via Purkinje fibres
- ## Right and left bundle branches
Which section of an ECG represents the atrial contraction?
- P wave
Which section of an ECG represents the ventricular contraction?
- QRS complex
Which section of an ECG represents ventricular repolarisation?
- T wave
What maintains resting potential of the heart?
- Transmembrane electrical gradient is maintained
- Interior of cell is negative with respect to outside of cell
- Caused by unequal distribution of ions inside vs outside cell
- Na+ much higher outside cell than inside cell
- Ca2+ much higher outside cell than inside cell
- K+ much higher inside cell than outside cell
- Maintained by ion selective channels, active pumps and exchangers
Outline the fast cardiac action potential
- Phase 0: depolarisation due to influx of Na+
- Phase 1: early repolarisation due to outward movement of K+
- Phase 2: plateau due to Ca2+ influx (from sarcoplasmic reticulum)
- Phase 3: repolarisation due to efflux of K+
- Phase 4: resting phase
What is the effect of class 1 drugs?
- Slows phase 0
- Prevents influx of Na+
- Slows conduction in tissue
- Minor effects on action potential duration
What is the effect of class 2 drugs?
- Diminishes phase 4 depolarisation and automaticity
- Beta blockers
- AP duration slightly lengthened
Give some examples of class 3 drugs
- Amiodarone
- Dofetilide
- Sotalol
What is the effect of class 3 drugs?
- Block K+ channels
- Prolong phase 3 repolarisation without altering phase 0
- Increase effective refractory period
- Increase AP duration
What is the effect of class 4 drugs?
- Calcium channel blockers
- Cause decrease in inward Ca2+ currents
- Slow phase 4 spontaneous depolarisation
- Affect plateau phase of action potential
- Slow conduction in tissues dependent on calcium currents e.g. AV node
Outline the slow cardiac action potential
- Funny current leads to spontaneous depolarisation (slow Na+ channels) in phase 4
- Calcium influx leads to depolarisation in phase 0
- Potassium efflux in phase 3 leads to repolarisation
How do calcium channel blockers affect the slow cardiac action potential?
- Slows down conduction velocity
- Refractory period increases
- Takes longer for next heartbeat to occur
Which drugs affect automaticity?
- Beta agonists
- Muscarinic agonists
- Adenosine
Outline the mechanisms of arrhythmogenesis (abnormal impulse generation)
- Abnormal impulse generation
- Leads to automatic rhythms such as enhanced normal automaticity (increased APs from SA node) and ectopic focus (AP arises from sites other than SA node)
- OR triggered rhythms (delayed afterdepolarisations or early afterdepolarisations)
Outline the mechanisms of arrhythmogenesis (abnormal conduction)
- Conduction block - can be first degree, second degree, third degree
- Re-entry - circus movement and reflection
Outline how abnormal anatomic conduction occurs
- Some patients are born with an extra circuit that connects the atria and ventricles
- Present only in small populations
- Leads to pre-excitation
- Wolf-Parkinson-White syndrome
- See a delta wave on ECG and palpitations
Outline AV nodal re-entrant tachycardia
- Most common supraventricular tachycardia
- Involves a slow pathway and a fast pathway in right atrium
- Can occur around a scar
Outline the action of drugs that treat abnormal generation of arrhythmias?
- Decrease phase 4 slope
- In pacemaker cells
- Raises threshold
Outline the action of drugs that treat arrhythmias due to abnormal conduction
- Decrease conduction velocity
- Increases effective refractory period
What are the goals for treating arrhythmias?
- Restore normal sinus rhythm and conduction
- Prevent more serious and possibly lethal arrhythmias from occurring
What are the uses of antiarrhythmic drugs?
- Decrease conduction velocity
- Change duration of effective resting potential
- Suppress abnormal automaticity
Give some examples of class 1B agents
- Lidocaine - iv only
- Mexiletine - orally
What are the effects of class 1B agents on cardiac activity?
- Fast binding offset kinetics
- No change in phase 0 in normal tissue (no tonic block)
- Action potential duration slightly decreased
- Increase threshold that needs to be reached before Na+ channels need to be activated
- Decrease phase 0 conduction in fast beating or ischaemic tissue
What are the effects of class 1B agents on ECG?
- None in normal
- Increased QRS in fast beating or ischaemic tissue
What are the uses of class 1B agents?
- Acute: ventricular tachycardia (especially during ischaemia)
- Not used in atrial arrhythmias or AV junctional arrhythmias
What are the side effects of class 1B agents?
- Dizziness
- Drowsiness
- Abdominal upset
Give some examples of class 1C agents
- Flecainide (propafenone)
- Can be taken orally or IV