CPRS20: Antiarrhythmic drugs Flashcards
What are the 4 classes of antiarrhythmic drugs?
Class 1: Na+ channel blockers
Class 2: B adrenergic receptor blockers
Class 3: K+ channel blockers
Class 4: Ca2+ channel blockers
At what stage does Na+ channel blockers (class 1 drugs) function?
Binds in activated (open) and inactivated state
The more frequently the channels are activated, the greater the degree of block
Decreased conduction velocity –> block tachycardias
What are the subtypes of class 1 antiarrhythmic drugs?
Class 1a (oldest type): procainamide, quinidine, disopyramide
Class 1b: lidocaine, mexiletine –> preferentially blcok premature beats
Class 1c: flecainide, encainide, propafenone –> decrease conduction
AE of class 1c drugs (flecainied, propafenone)?
Proarrhythmia
AE of propafenone: worsen heart failure
Structural similarities to propranolol (weak B adrenergic receptor blocking activitity -ve inotropic)
MoA of Class 1a drugs (procainamife, quinidine, disopyramide)
Inhibit increased automaticity, moderately decrease conduction
Block K channels: decrease rate of repolarization of cardiac cells, increase duration of action potential, increase effective refractory period (ERP)
AE of class 1a drugs (procainamide, quinidine, disopyramide)?
Pro arrhythmia: due to inhibition of K+ channels –> prolongation of the repolarization phase –> early afterdepolarization (risk of inducing torsades de pointes arrhythmia)
Anticholinergiv effect: tachycardia
GI disturbance
Lupus related symptoms: arthralgia and arthritis due to long term use of procainamide
Decreased force of contraction of heart: disopyramide>quinidine>procainamide
What is MoA of class 2 antiarrhythmic drugs?
Oppose B adrenergic stimulation
Decrease HR, increase AVN conduction time, decrease intracellular calcium overload (prevent delayed afterdepolarization automaticity)
Selective B1 adrenergic receptor blockers e.g. metoprolol, esmolol
Non selective B adrenergic receptor blockers e.g. propranolol –> for arrhythmia induced by adrenaline induced hypokalemia associated with severe stress (acute MI or resuscitation from cardiac arrest)
What is AE of class 2 antiarrhythmic drugs?
Decreased force and rate of contraction of heart: cautious in patients with heart failure
Bronchospasm: C/I in patients with asthma or other forms of obstructive airway disease
Hypoglycemia: C/I in patients with diabetes
What is MoA of class 3 antiarrhythmic drugs and examples of drug names?
K+ channel blockers: amiodarone, dofetilitide
Decrease rate of repolarization: increase action potential duration, increase effective refractory period, decrease automaticity, disable reentry
MoA and important risk for both dofetilitide and amiodarone?
Dofetilide: potent and pure blocker for rapidly activating delayed rectifier K+ channel
Risk of torsades de pointes: cautious with hypoK, avoided in patients with advanced renal failure or taking inhibitors of renal cation transport e.g. cimetidine
Amiodarone: in addition of K+ channel blockade. Block inactivated Na+ channels, weak adrenergic blocking activity, weak calcium channel blocking activity
Low incidence of torsades de pointes
Amiodarone AE and drug interactions
Pulmonary fibrosis
Hypersensitivity hepatitis
Photosensitivity
Corneal deposits
Thyroid abnormalities
Proarrhythmia
Interacts with CYP3A4
Increased by drugs inhibiting CYP3A4 (cimetidine)
Reduced by drugs inducing CYP3A4 (rifampin)
Amiodarone increases plasma levels of drugs that depend on CYP3A4 for metabolism (statins, warfarin, digoxin)
What is the MOA of class 4 antiarrhythmic drugs and give examples
CCB: verapamil, diltiazem
Decrease HR, AVN conduction velocity, decrease calcium overload (effective for DAD mediated arrhythmia)
What is the AE of class IV antiarrhythmic drugs?
Decrease force and rate of contraction of heart, AV block, hypotension, peripheral edema
Leads to heart failure
What is the MOA of adenosine?
Activates presynaptic purinergic receptors on sympathetic nerve terminals: decrease release of noradrenaline, decrease normal automaticity
Activate A1 receptors on SA and AVN: inhibit AC, decrease cAMP production, decrease Ca2+ overload
Activate K+ channels in SA and AVN: increase maximum diastolic potential, prolong phase 4 depolarization, decrease conduction velocity
What is AE of adenosine?
Flushing, hypotension due to activation of A2 receptors in vascular smooth muscle cells –> increases intracellular cAMP –> vasodilation
Chest pain and SOB
