Q3 LONG ANSWER 10M ★ High-yield

Classify antiarrhythmic drugs. Describe amiodarone and add a note on proarrhythmia.

Pharmacology · 2nd Professional — Para-Clinical

Vaughan Williams Classification

Class	Mechanism	Drugs	ECG effect
IA	Sodium channel block, moderate; prolong repolarisation	Quinidine, procainamide, disopyramide	QRS and QT prolonged
IB	Sodium channel block, weak; shorten repolarisation; act on ischaemic and depolarised tissue	Lignocaine, mexiletine, phenytoin	Little change; QT may shorten
IC	Sodium channel block, marked; little effect on repolarisation	Flecainide, propafenone	QRS markedly prolonged
II	Beta-blockade	Propranolol, metoprolol, esmolol	PR prolonged; rate slowed
III	Potassium channel block; prolong repolarisation and refractoriness	Amiodarone, sotalol, dofetilide, dronedarone	QT prolonged
IV	Calcium channel block (nodal tissue)	Verapamil, diltiazem	PR prolonged
Unclassified	—	Adenosine, digoxin, magnesium, atropine, ivabradine	Varies

Amiodarone

Class III principally, but has properties of all four classes — sodium and calcium channel block, beta-blockade and potassium channel block; the most broadly effective antiarrhythmic
Uses — atrial fibrillation (conversion and maintenance), ventricular tachycardia and fibrillation, and in cardiac arrest refractory to defibrillation; effective where structural heart disease makes other agents unsafe
Remarkable pharmacokinetics — volume of distribution about 5,000 L and a half-life of 25 to 100 days; a loading regimen is essential and effects persist for months after stopping

System	Adverse effect
Thyroid	Both hypo- and HYPERthyroidism — each molecule carries two iodine atoms, giving an enormous iodine load; thyroid function must be checked before and every 6 months
Lung	Pulmonary fibrosis and pneumonitis — the most feared; may be irreversible and fatal
Liver	Raised transaminases; hepatitis; cirrhosis
Eye	Corneal microdeposits in almost all patients — usually harmless, causing haloes; rarely optic neuropathy
Skin	Photosensitivity and a slate-grey discolouration of exposed skin
Neurological	Peripheral neuropathy, tremor, ataxia
Cardiac	Bradycardia, heart block; QT prolongation but a low risk of torsades compared with other class III agents
Interactions	Raises digoxin and warfarin levels substantially — both doses must be reduced

CLINICAL PEARL

Amiodarone is the most effective antiarrhythmic and the most toxic, and the decision to use it is a decision to monitor for years. Its half-life of weeks means toxicity accumulates slowly and persists long after withdrawal. It is reserved for arrhythmias that genuinely threaten life or quality of life, with baseline and periodic thyroid, liver, lung and eye assessment built into the prescription from the start.

Proarrhythmia and QT Prolongation

Antiarrhythmic drugs can cause arrhythmia — the central paradox of the class
Torsades DE pointes — polymorphic ventricular tachycardia with a twisting axis, occurring on a background of prolonged QT; caused by class IA and III drugs, and by many non-cardiac drugs
Non-cardiac drugs prolonging QT — erythromycin and clarithromycin, fluoroquinolones, antipsychotics (haloperidol), antidepressants, ondansetron, antifungals, antimalarials
Precipitated by hypokalaemia, hypomagnesaemia, bradycardia, female sex, congenital long QT syndrome, and combining two QT-prolonging drugs
Treatment — stop the drug, intravenous magnesium sulphate, correct potassium, and increase the rate by pacing or isoprenaline; ordinary antiarrhythmics make it worse
The cast trial showed that flecainide and encainide, given after myocardial infarction to suppress ventricular ectopics, increased mortality — the classic warning against treating a surrogate marker rather than an outcome

Drugs for Specific Arrhythmias

Arrhythmia	Drug of choice
Paroxysmal supraventricular tachycardia	Vagal manoeuvres, then adenosine (rapid intravenous bolus; half-life about 10 seconds; causes transient flushing, chest tightness and a sense of impending doom — the patient must be warned)
Atrial fibrillation — rate control	Beta-blocker or verapamil/diltiazem; digoxin if there is heart failure or the patient is sedentary
Atrial fibrillation — rhythm control	Amiodarone; flecainide if the heart is structurally normal
Ventricular tachycardia	Amiodarone or lignocaine; DC cardioversion if unstable
Ventricular fibrillation	Defibrillation first; adrenaline and amiodarone as adjuncts
Torsades de pointes	Magnesium sulphate
Digoxin-induced arrhythmia	Correct potassium; phenytoin or lignocaine; Fab fragments
Bradycardia and heart block	Atropine; isoprenaline; pacing

Adenosine and Other Agents

Drug	Action	Practical points
Adenosine	Activates A1 receptors → transient complete AV block	Half-life about 10 seconds; must be given as a rapid bolus with a saline flush into a large vein; causes flushing, chest tightness and a sense of impending doom, so the patient must be warned. Contraindicated in asthma
Magnesium sulphate	Stabilises the membrane	The treatment of torsades DE pointes, and useful in digoxin toxicity
Atropine	Vagolytic	Symptomatic bradycardia and AV block
Ivabradine	Inhibits the If "funny" current in the SA node	Slows the rate without negative inotropy; causes luminous visual phenomena
Digoxin	Vagal enhancement	Rate control at rest; poor during exertion

Applied Aspects

Always correct potassium and magnesium first — many arrhythmias resolve with electrolyte correction alone, and no antiarrhythmic works reliably in their presence
In atrial fibrillation, rate control is as good as rhythm control for most patients, and carries less drug toxicity
Anticoagulation, not the antiarrhythmic, prevents the stroke in atrial fibrillation; the decision is made on the CHA2DS2-VASc score and is independent of whether rhythm is restored
Baseline and follow-up tests before amiodarone — thyroid, liver, chest radiograph, and eye examination; and warn about sun protection
Review every drug list for QT-prolonging combinations, particularly when adding an antibiotic or antiemetic to a patient already on an antiarrhythmic or antipsychotic
A defibrillator, not a drug, is the treatment for pulseless ventricular tachycardia and fibrillation; drugs are adjuncts and never delay defibrillation
Adenosine is contraindicated in asthma (bronchospasm) and its effect is blocked by theophylline and potentiated by dipyridamole
Verapamil must never be given for a broad-complex tachycardia of uncertain origin — if it is ventricular tachycardia, the result may be fatal hypotension
An implantable defibrillator outperforms every antiarrhythmic drug for prevention of sudden death in high-risk patients, and drugs are increasingly used to reduce shocks rather than as primary treatment

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