Yang Yang AP and Antiarrhythmics Flashcards
Important ion channels in the heart
-Sodium channels
-Calcium channels
-Potassium channels
-HCN channels
-hERG channels (avoid targeting when developing new drugs)
Potassium concentration outside the cell
5 mM
Sodium concentration outside the cell
142 mM
Calcium concentration outside the cell
5 mM
Chloride concentration outside the cell
103 mM
Potassium concentration inside the cell
148 mM
Sodium concentration inside the cell
10 mM
Calcium concentration inside the cell
<1 uM
Chloride concentration inside the cell
4 mM
Voltage value inside the cell
-70 mV
Voltage value outside the cell
0 mV
What are pacemaker cells?
-Specialized, non-contractile cells
-Physiologically depolarized
-High automaticity
-Ca2+-dependent spikes
What are ventricular myocytes?
-Contractile cells
-Hyperpolarized
-Low automaticity
-Na+-dependent spikes
Common arrhtyhmias
-Atrial sinus arrhythmia
-Re-entry arrhythmias
-Atrial fibrillation
-Wolf-Parkinson White
-Monomorphic ventricular tachycardia
-AV nodal re-entrant tachycardia
-Premature ventricular complexes
Re-entry arrhythmia requirements
-Multiple parallel pathways
-Unidirectional block
-Conduction time greater than ERP (effective refractory period)
What are class 1 antiarrhythmic drugs?
Na+ channel blockers
What are class 2 antiarrhythmic drugs?
Beta-adrenergic antagonists
What are class 3 antiarrhythmic drugs?
Agents that prolong refractory period (K+ channel blockers)
What are class 4 antiarrhythmic drugs?
Ca2+ channel blockers
Class 2 antiarrhythmic drug mechanism of action
-Beta adrenergic blockers
-Slows pacemaker and Ca2+ currents in SA, AV node
-Increase refractoriness of SA, AV node
-Increase P-R interval
-Arrhythmias involving catecholamines (epinephrine, norepinephrine, etc . . .)
Class 4 antiarrhythmic drug mechanism of action
-Ca2+ channel blockers
-Frequency-dependent block
-Increase refractoriness of AV node and P-R interval
-Protect ventricular rate from atrial tachycardia
Beta blockers used as antiarrhythmics
-Esmolol
-Acebutolol
-Propranolol
Beta blocker clinical use as antiarrhythmics
-Arrhythmias involving catecholamines
-Atrial arrhythmias (protect ventricular rate)
-Post-MI prevention of ventricular arrhythmias
-Prophylaxis in Long QT syndrome (catechol.-sens)
Calcium channel blockers used as antiarrhythmics
-Verapamil
-Diltiazem
Calcium channel blocker clinical use as antiarrhythmics
-Block re-entrant arrhythmias involving AV node
-Protect ventricular rate in atrial flutter and atrial fibrillation
Class 1A antiarrhythmic effect on action potential
-Mixed block: Na+ and K+ channels
-Blocks open state
-Moderate, incomplete dissociation
-Widen QRS
-Prolonged QT
Class 1B antiarrhythmic effect on action potential
-Na+ channel block
-Blocks open and inactivated state
-Rapid, complete dissociation
-Slight narrowing of action potential
-No clinically significant effect on ECG
Class 1C antiarrhythmic effect on action potential
-Strong Na+ channel block
-Blocks open state
-Very slow, incomplete dissociation
-Widen QRS
Class 1A antiarrhythmic drugs
-Quinidine
-Procainamide
-Disopyramide
Class 1B antiarrhythmic drugs
-Lidocaine
-Mexiletine
-Tocainide
-Phenytoin
Class 1C antiarrhythmic drugs
-Flecainide
-Propafenone
-Moricizine
Quinidine clinical pearls
-2-8% risk of torsades de pointes
-Aniti-muscarinic activity
Procainamide clinical pearls
-Lupus-like syndrome
-Ganglionic blocker
Disopyramide clinical pearls
-Anti-muscarinic activity
Lidocaine clinical pearls
-IV only; not effective orally
-Among top choices for rapid control of ventricular arrhythmias
-Only ventricular, not atrial
Mexiletine clinical pearls
-Orally available, similar to lidocaine in efficacy
Flecainide clinical pearls
-Ventricular and supraventricular
-Orally available
Propafenone clinical pearls
-Ventricular and supraventricular
-Beta receptor blocking activity
-Orally available
Class 3 antiarrhythmics mechanism of action
-Block IKr, prolong action potential duration and Q-T interval
-Increases effective refractory period
-In re-entrant circuit, increased ERP above conduction time around circuit will terminate re-entry
Why can class 3 antiarrhythmics cause TDP?
-IKr block induces EADs and triggered upstrokes
-Multifocal/polymorphic ventricular tachycardia
-Can degenerate into ventricular fibrillation
Class 3 antiarrhythmic drugs
-Amiodarone
-Dronedarone
-Ibutilide
-Sotalol
-Dofetilide
Amiodarone clinical use
-Top choice for rate control in A-fib, suppression of post-MI ventricular arrhythmias
Dronedarone clinical use
A-fib
Sotalol clinical use
Prevent A-fib re-occurrence
Ibutilide clinical use
Convert A-fib to sinus rhythm
