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
What are the effects of class 1C agents on cardiac activity?
- Very slow binding offset kinetics (>10s)
- Substantially decreases phase 0 (Na+ conduction)
- Decrease automaticity and increase threshold
- Increase action potential duration (K+) and refractory period, especially in rapidly depolarising atrial tissue
What are the effects of class 1C agents on ECG?
- Increased PR interval
- Increased QRS complex
- Increased QT interval
What are the uses of class 1C drugs?
- Wide spectrum
- Used for supraventricular arrhythmias (fibrillation and flutter)
- Premature ventricular contractions
- Wolf-Parkinson-White syndrome
What are the side effects of class 1C drugs?
- Pro-arrhythmia and sudden death (especially with chronic use and in structural heart disease)
- Increased ventricular response to supraventricular arrhythmias (flecainide flutter)
- CNS and gastrointestinal effects
Give some examples of class II agents
- Propranolol - oral and IV
- Bisoprolol - oral
- Metoprolol - 5mg IV, oral too
- Esmolol - IV only (very short half life)
What are the cardiac effects of class II agents?
- Increased APD and refractory period in AV node to slow Av conduction velocity
- Decrease phase 4 depolarised agent (catecholamine dependent)
What are the effects of class II agents on ECG?
- Increased PR interval
- Decreased HR
What are the uses of class II agents?
- Treating sinus and catecholamine dependent tachycardia
- Converting re-entrant arrhythmias at AV node
- Protecting ventricles from high atrial rates (slow AV conduction) in atrial flutter or atrial fibrillation
What are the side effects of Class II agents?
- Bronchospasm
- Hypotension
- Don’t use in partial AV block or acute heart failure
Give some examples of Class III agents
- Amiodarone - oral or IV (long half life)
- Sotalol - oral absorption
What are the cardiac effects of class III agents?
- Increase refractory period and action potential duration by slowing K+ movement
- Decrease phase 0 and conduction (Na+)
- Increase threshold
- Decrease phase 4 (beta block and calcium channels blocked)
- Decrease speed of AV conduction
What are the effects of class III agents on ECG?
- Increase PR interval
- Increase QRS complex
- Increase QT interval
- Decrease HR
What are the uses of amiodarone?
- Very wide spectrum but useful for most arrhythmias
What are the side effects of amiodarone?
- Many serious side effects that may increase with time
- Pulmonary fibrosis
- Hepatic injury
- Increase LDL cholesterol
- Thyroid disease
May need to reduce dose of digoxin and monitor warfarin more closely
What are the cardiac effects of sotalol?
- Increases action potential duration and refractory period in atrial and ventricular tissue
- Slow phase 4 (beta blocker)
- Slow AV conduction
What are the effects of sotalol on the ECG?
- Increases QT interval
- Decrease HR
What are the uses of sotalol?
- Wide spectrum
- Supraventricular and ventricular tachycardia
What are the side effects of sotalol?
- Proarrhythmic
- Fatigue
- Insomnia
What are some examples of class IV agents?
- Verapamil - oral or IV
- Diltiazem - oral
What are the cardiac effects of class IV agents?
- Slow conduction through AV (Ca2+)
- Increase refractory period in AV node
- Increase slop of phase 4 in SA to slow HR
What are the effects of class IV agents on ECG?
- Increased PR interval
- Increased or decreased HR (depends on BP response and baroreflex)
What are the uses of class IV agents?
- Control ventricles during supraventricular tachycardia
- Convert supraventricular tachycardia (re-entry around AV)
What are the side effects of class IV drugs?
- Caution when partial AV block is present. Can get asystole if beta blocker is on board
- Caution when hypotension, decreased cardiac output or sick sinus
- Some gastrointestinal problems
Outline the administration of adenosine
- Rapid IV bolus
- Very short half life (seconds)
What is the mechanism of action of adenosine?
- Natural nucleoside that binds A1 receptors
- Blocks adenylyl cyclase
- Reduces cAMP
- Activates K+ currents in AV and SA node
- Causes hyperpolarisation
- Decreases HR
- Leads to decreased Ca2+ currents
- Increases refractory period in AV node
What are the cardiac effects of adenosine?
- Slows AV conduction
What are the uses of adenosine?
- Convert re-entrant supraventricular arrhythmias
- Diagnosis of coronary artery disease
How is ivabradine administered?
- Orally in 2.5mg bd
- Dosing up to 10 mg bd
What is the mechanism of action of ivabradine?
- Blocks funny current ion channels highly expressed in sinus node
What are the cardiac effects of ivabradine?
- Slows sinus node
- BP not affected
What are the side effects of ivabradine?
- Flashing lights
- Teratogenicity not known
What are the uses of ivabradine?
- Reduce inappropriate sinus tachycardia
- Reduce heart rate in heart failure and angina
What is the mechanism of action of digoxin?
- Enhances vagal activity
- Increases K+ currents and decreases Ca2+ currents to increase refractory period
- Slows AV conduction
- Slows HR
What are the uses of digoxin?
- Treatment to reduce ventricular rates in atrial fibrillation and flutter
What is the mechanism of action of atropine?
- Selective muscarinic antagonist
What are the cardiac effects of atropine?
- Block vagal activity to speed AV conduction and increase HR
- Used to treat vagal bradycardia
Which drugs should be prescribed for AF?
For rate control:
- Bisoprolol first line
- Verapamil if asthma
- Diltiazem and digoxin
For rhythm control:
- Sotalol
- Flecainide with bisoprolol
- Amiodarone
Should flecainide be used alone in atrial flutter?
- No
- Give AV nodal blocking drugs to reduce ventricular rates in atrial flutter
Which IV drugs are given to treat ventricular tachycardia?
- Depends on what drugs have already been prescribed
- IV metoprolol if not on bisoprolol
- IV lignocaine if not on mexiletine
- Amiodarone if not taking it and already on bisoprolol/mexiletine
- IV metoprolol/lignocaine or amiodarone
What is the best drug to treat Wolf-Parkinson-White syndrome?
- Flecainide
- (Amiodarone)
- Avoid AV nodal blocking drugs due to risk of pre-excited AF and therefore VF
Which drugs are used acutely in re-entrant narrow complex tachycardia?
- Adenosine
- Verapamil
- Flecainide
Which drugs are used to treat chronic re-entrant narrow complex tachycardia?
- Bisoprolol, verapamil
- Sotalol
- Flecainide
- Amiodarone
Which drugs are given to treat ectopic beats?
- Bisoprolol first line
- Calcium channel blockers if asthma
- Flecainide and sotalol with amiodarone last resort
Which drugs are used to treat sinus tachycardia?
- Ivabradine
- Bisoprolol, verapamil
