EP3 Anti-arrhythmic drugs Flashcards
What are the 3 main mechanisms for tachyarrhythmias?
-Abnormal automaticity
-Triggered activity
-Reentry
Vaughn-Williams classification of AADs
-Groups most AADs into 4 classes based on their mechanism
Describe the action of Class I AADs (Na channel blockers)
-Block Na channels in the open or inactivated state
-This decreases the rise of phase 0 depolarisation and slows conduction velocity
-Class I AADs divided into 1A,1B, 1C
Action of Class 1A AADs (Na channel blockers)?
Class 1A drugs
-moderately depress phase 0 depolarisation by blocking fast Na channels
-prolong repolarisation by blocking K channels
-results in prolonged action potential and refractory period
Examples and side effects of Class 1A AADs (Na channel blockers)?
-Procainamide
-Quinidine (blurred vision, headache, tinnitus)
-Disopyramide (anti-cholinergic effects: blurred vision, constipation, dry mouth)
Uses of Class 1A AADs (Na channel blockers)?
-Treat VT
-Treat recurrent AF
Action of Class 1B AADs (Na channel blockers)?
-Shorten repolarisation by blocking Na channels that activate during late phase 2 of the action potential
-shorten duration of action potential and refractory period
Examples and side effects of Class 1B AADs (Na channel blockers)?
-Lidocaine (CNS toxicity: seizures)
-Mexiletine (nausea and vomiting)
Uses of Class 1B AADs (Na channel blockers)?
-Treatment of Ventricular arrhythmias
Action of Class 1C AADs (Na channel blockers)?
-Powerful fast Na channel blockers
-Significantly depress phase 0 depolarisation
-Inhibit His-Purkinje conduction system
-Have a limited effect on repolarisation and refractory period
Examples and side effects of Class 1C AADs (Na channel blockers)?
-Flecainide
-Propafenone
(Dizziness, blurred vision, nausea)
Uses of Class 1C drugs (Na channel blockers)
-Treatment of refractory ventricular arrhythmias
What is a risk of all Class 1 AADs (Na channel blockers)?
-They can be pro-arrhythmogenic
Action of Class 2 AADs (beta blockers)?
-Act on beta 1 receptors
-Prevent the action of catecholamines on the heart
-Depress sinus node automaticity and slow conduction through AV node which causes decreased heart rate and contractility
Uses of Class 2 AADs (beta blockers)?
-Used to treat arrhythmias provoked by increased sympathetic activity
Examples of Class 2 AADs (beta blockers)?
-Propranolol
-Metoprolol
-Atenolol
-Esmolol (given IV in emergencies due to fast onset and short half life)
Action of Class 3 AADs (K channel blockers)?
-Block K channels that are responsible for phase 3 repolarisation
-This increases duration of action potential and refractory period
Uses of Class 3 AADs (K channel blockers)?
-Used to treat supraventricular/ventriuclar tachyarrhythmias
-Also AF/atrial flutter
Examples and side effects of Class 3 AADs (K channel blockers)?
-Amiodarone (pulmonary fibrosis, skin discolouration, neuropathy, hepatotoxicity, corneal micro-deposits, thyroid dysfunction)
-Dronedarone (less lipophilic, shorter half life, no iodine, not as effective as ami)
-Sotalol (Block B receptors)
-Dofetilide, Ibutilide (most selective K channel blockers, but pro-arrhythmogenic)
Action of Amiodarone (K channel blocker)
-Blocks K, Na, Ca channels
-Blocks alpha and beta receptors
-But has long half life so can stay in tissue for months
Action of Class 4 AADs (Ca channel blocker)
-Block voltage-sensitive Ca channels during depolarisation in SA and AV nodes
-This causes slower conduction and reduced contractility of heart
Uses of Class 4 AADs (Ca channel blocker)?
-Used to treat SVT and AF
Examples and side effects of Class 4 AADs (Ca channel blocker)?
-Nondihydropyridine calcium channel blockers (e.g. Verapamil, Diltiazem)
Which AADs do not fit into classes?
-Digoxin
-Adenosine
-Magnesium sulphate
Action of Digoxin
-Inhibits NA/K pump by binding to K binding site
-Causes increased intracellular Na
-Casues Na/Ca exchanger to pump Na out and Ca in
-Increased intracellular Ca causes increased myocardial contractility
-Also stimulates parasympathetic system, increases activity of Vagus nerve, slowing Sinus discharge rate and decreased AV conduction
Uses of Digoxin
-Heart failure
-AF
Action of Adenosine
-Stimulates A1 adenosine receptors found in atrium, SA, AV node
-Causes decreased automaticity and conduction velocity and prolonged refractory period
Uses of Adenosine
-Short half life, given IV
-Treats acute SVT
-Non-toxic
-Side effects: chest pain, hypotension
Action of Magnesium sulphate
-Transports Na, K, Ca across cell membranes
-Mechanism unknown
Uses of Magnesium sulphate
-Treats Torsades de Pointes
and digoxin-induced arrhythmias
