Antiarrhythmic drugs Flashcards
Sources
https://wchh.onlinelibrary.wiley.com/doi/10.1002/psb.1828
https://bnf.nice.org.uk/drugs/amiodarone-hydrochloride/
https://go.drugbank.com/drugs/DB01118
What are the different classes of antiarrhythmic drugs?
Class I
Class II
Class III
Class IV
Class V
According to the Vaughan Williams classification
Which subgroup are Class I drugs further subdivided into?
Ia
Ib
Ic
Subdivided according to the speed at which they cause association/dissociation in non-nodal cardiac myocytes
Which type of antiarrhythmic drugs fall under class I?
Sodium channel blockers
Block Na+ influx
How fast do class Ia agents act?
Act at an intermediate speed
Give examples of class Ia agents
Quinidine
Procainamide
How fast do class Ib agents act?
Fastest acting
How fast do class Ic agents act?
Slow
Give examples of class Ib agents
Lidocaine
Mexiletine
Give an example of a class Ic agents
Flecainide
Which class I drugs are not commonly used in clinical practice?
Ia
They are anticholinergics
What can procainamide be used for?
Mx of ventricular and supraventricular tachyarrhythmias
Can be given PO, IM or IV
What type of reaction can procainamide commonly cause in some patients?
Lupus-like reaction
What can quinidine be used for?
Prevention of ventricular arrhythmias most notably in Brugada syndrome and idiopathic VF
What is lidocaine useful for apart from being a local anaesthetic agent?
Mx of VT when given IV
What are the adverse effects of quinidine?
Prolonged QT interval (can be useful in in managing short QT syndromes)
Nausea
Abdominal cramps
Increases digitalis toxicity
What are the adverse effects of IV lidocaine?
CNS excitation/depression
Cardiovascular instability (inc. arrhythmias and bradycardia)
Hypotension
What is the name of the drug that is an analogue of lidocaine but with oral bioavailability?
Is it licensed for use in the UK
Mexiletine
Not licensed for use in UK but can be imported on a case-by-case basis
What are class Ic drugs like flecainide used to manage?
Paroxysmal AF
What are important contraindications for class Ic drugs?
Previous MI
Sustained ventricular arrhythmias
Life threatening VT or shock can be induced in these settings
Which type of antiarrhythmic drugs fall under class II?
Beta blockers
They block catecholamines at beta1-adrenoceptors prolonging repolarisation
What are the indications for class II drugs?
Mx of tachyarrhythmias - Tx + prevention
Rate control in AF and atrial flutter
Can also be beneficial in chronic HF, after a MI and in glaucoma
Name the non-selective class II drugs
Propranolol (10-40 mg TDS-QDS)
Carvedilol (3.125-25mg BD - max 50 mg if < 85kg)
Labetalol (50-400mg BD)
Sotalol (40-160mg BD)
Name the cardioselective class II drugs
Bisoprolol (1.25-20 mg OD)
Atenolol (25-50 mg BD)
Metoprolol (50-100mg BD-TDS)
Which type of antiarrhythmic drugs fall under class III?
Potassium channel blockers
In the cardiac action potential, what are K+ channels responsible for?
Repolarisation
Essentially it allows the heart to become depolarised again
What effect does blocking the K+ channels have on the action potential?
Slows repolarisation
Increases AP and refractory period
Slows conduction
Translate to a prolonged QT interval on ECG
Give examples of class III drugs
Amiodarone
Sotalol (40-160mg BD)
Dronedarone
What are the indications for amiodarone?
Rhythm control in AF/atrial flutter
Haemodynamically stable VF
What are the adverse effects of amiodarone esp. after prolonged use (i.e., > 6 months)?
Arrhythmias
Hepatic disorders - abnormal liver enzymes
Hyperthyroidism
Pulmonary fibrosis
Photosensitivity
Skin reactions - blue-grey skin discolourations
Corneal microdeposits
Peripheral neuropathy
Does not improve mortality in patients with HF
What are the rare side effects of amiodarone?
Bronchospasm in patients with respiratory failure
Headache
Idiopathic intercranial HTN
Nerve disorders
SIADH
What are the contraindications for class III drugs?
Pre-existing prolonged QT interval - worsening of this may cause polymorphic VT
Bradycardia
AV block
In which group of patients should sotalol be avoided?
HF
Significant renal impairment
Hypokalaemia
Apart from the generic class III drugs side effect, what are the more specific side effects of sotalol?
Chest pain
Breathlessness
Palpitations
Which type of antiarrhythmic drugs fall under class IV?
CCBs
Mainly the non-dihydropyridines
The dihydropyridines (e.g., amlodipine, nimodipine) do not have anti-arrhythmic properties
Give examples of class IV drugs
Diltiazem (PO 60 mg TDS/60mg BD in elderly - max 360mg per day)
Verapamil (PO 40-120mg TDS OR slow IV infusion 5-10mg over 2 mins/over 3 mins in elderly)
What are the indications of class IV drugs?
Prevention and Tx of SVTs:
- rate control in AF/atrial flutter
- fascicular VT
Helpful where beta-blockers are containdicated (e.g., in asthma) but should not be used concurrently with beta blockers due to risk of asystole
What are the contraindications of class IV drugs?
HF - as they reduce cardiac contractility
What are the adverse effects of class IV drugs?
Flushing
Dizziness
Headaches
Bradycardia
AV blocks
What additional side effects can verapamil cause?
Constipation
Rash
Nausea
What are class V agents?
Drugs that do not fit into the Vaughan Williams classification
Give examples of class V agents
Digoxin
Adenosine
What is the mechanism of digoxin?
Reduces HR via vagal effects
Mechanism not completely understood
In which conditions is digoxin commonly used?
AF (rate control)
Atrial flutter
NOTE: it is not an anti-arrhythmic per se
Which drugs can potentiate the effects of digoxin?
Quinidine
Amiodarone
CCBs
Beta blockers
Which condition can potentiate the effect of digoxin?
Hypokalaemia
What can digoxin toxicity cause?
Both brady- and tachyarrhythmias (atrial tachycardia and bidirectional VT)
In which conditions is digoxin contraindicated?
AV block
Wolff-Parkinson-White syndrome
When should digoxin be given with caution and its dose adjusted?
In the elderly
In renal impairment
What is adenosine?
A purine nucleoside
Made from the breakdown of ATP
What is the pharmacodynamics of adenosine?
binds Gi-protein type 1 receptors in cardiomyocytes
allows rapid K+ efflux and rapid hyperpolarisation and blocks Ca2+ influx
The reduces HR and conduction velocity by blocking AV node
What is the half-life of adenosine?
10 seconds
(very short)
How is adenosine commonly administered and used?
Commonly administered IV as a bolus in the management of SVT: either by cardioverting re-entrant tachycardias, or temporarily slowing the tachycardia to allow assessment of the underlying rhythm
What can adenosine cause and what are the side effects associated with this?
Vasodilatation
- headaches
- flushing
Can also cause ‘feeling of impending doom’ as it cause bronchospasm
What are the dosing of lidocaine when being used to treat arrhythmias
Ventricular arrhythmias, especially after myocardial infarction in patients without gross circulatory impairment
for lidocaine hydrochloride
Initially by intravenous injection
Adult
100 mg, to be given as a bolus dose over a few minutes, followed immediately by (by intravenous infusion) 4 mg/minute for 30 minutes, then (by intravenous infusion) 2 mg/minute for 2 hours, then (by intravenous infusion) 1 mg/minute, reduce concentration further if infusion continued beyond 24 hours (ECG monitoring and specialist advice for infusion), following intravenous injection lidocaine has a short duration of action (lasting for 15–20 minutes). If an intravenous infusion is not immediately available the initial intravenous injection of 100 mg can be repeated if necessary once or twice at intervals of not less than 10 minutes.
Ventricular arrhythmias, especially after myocardial infarction in lighter patients or those whose circulation is severely impaired
for lidocaine hydrochloride
Initially by intravenous injection
Adult
Initially 50 mg, to be given as a bolus dose over a few minutes, followed immediately by (by intravenous infusion) 4 mg/minute for 30 minutes, then (by intravenous infusion) 2 mg/minute for 2 hours, then (by intravenous infusion) 1 mg/minute, reduce concentration further if infusion continued beyond 24 hours (ECG monitoring and specialist advice for infusion), following intravenous injection lidocaine has a short duration of action (lasting for 15–20 minutes). If an intravenous infusion is not immediately available the initial intravenous injection of 50 mg can be repeated if necessary once or twice at intervals of not less than 10 minutes.
What are the dosing of amiodarone?
Treatment of arrhythmias, particularly when other drugs are ineffective or contra-indicated
PO
200 mg 3 times a day for 1 week, then reduced to 200 mg twice daily for a further week, followed by maintenance dose, usually 200 mg daily or the minimum dose required to control arrhythmia
IV
Initially 5 mg/kg, to be given over 20–120 minutes with ECG monitoring, subsequent infusions given if necessary according to response; maximum 1.2 g per day.
Ventricular fibrillation or pulseless ventricular tachycardia refractory to defibrillation (for cardiopulmonary resuscitation)
IV
Initially 300 mg, dose to be given over at least 3 minutes, dose should be given from a pre-filled syringe or diluted in 20 mL Glucose 5%, then 150 mg if required, consult Resuscitation Council (UK) guidelines for further details.
What is the dosing of digoxin?
Rapid digitalisation, for atrial fibrillation or flutter
0.75–1.5 mg in divided doses, dose to be given over 24 hours, reduce dose in the elderly.
Maintenance, for atrial fibrillation or flutter
Maintenance 125–250 micrograms daily, dose according to renal function and initial loading dose, reduce dose in the elderly.
Heart failure (for patients in sinus rhythm)
62.5–125 micrograms once daily, reduce dose in the elderly
Emergency loading dose, for atrial fibrillation or flutter
Loading dose 0.75–1 mg, to be given over at least 2 hours, then (by mouth) maintenance - reduce dose in elderly
What is the dosing of adenosine?
Rapid reversion to sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory conducting pathways (e.g. Wolff-Parkinson-White syndrome),
Used to aid to diagnosis of broad or narrow complex supraventricular tachycardias
Initially 6 mg, administer into central or large peripheral vein and give over 2 seconds, cardiac monitoring required, followed by 12 mg after 1–2 minutes if required, then 12 mg after 1–2 minutes if required, increments should not be given if high level AV block develops at any particular dose
Rapid reversion to sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory conducting pathways (e.g. Wolff-Parkinson-White syndrome) in patients with a heart transplant,
Aid to diagnosis of broad or narrow complex supraventricular tachycardias in patients with a heart transplant
Initially 3 mg, administer into a central or large peripheral vein and give over 2 seconds, followed by 6 mg after 1–2 minutes if required, then 12 mg after 1–2 minutes if required, patients with a heart transplant are very sensitive to the effects of adenosine.
All are RAPID IV INFUSIONS
What is adenosine used to treat?
Supraventricular tachycardia (SVT)
