antiarrhythmic drugs Flashcards
What are the classes of antiarrhythmic drugs?
Class 1 (Na channel blockers), Class II (beta blockers), class III (Prolongation of phase 2), class IV (Ca channel blockers), unclassified drugs (ie. Adenosine)
What do class I drugs do?
Block Na channels in fast response cells, and to a lesser extent they block L-type Ca channels in slow response cells. All class I drugs decrease conduction rate and increase refractory period
What are examples of class Ia drugs?
quinidine, procainamide, disopyramide (quit procrastinating dis)
What do class Ia drugs do?
slow the upstroke of the fast response (by blocking Na channels), and they also delay the onset of repolarization (by blocking K channels, a class III effect)
How do Class Ia drugs prolong refractory period?
(i) via classic, use-dependent mechanism, similar to local anesthetics in action. (ii) because depolarization (phase 2 duration) is prolonged
What other actions does Quinidine have that are not related to Na channel block?
Prolongs AP duration by blocking K channels, vagal inhibitor (anti-choliergic) and it is an alpha-adrenergic receptor antagonist
Class Ib drug examples
lidocaine, mexiletine, phenytoin (little mexican phenytoin)
Class Ib actions
Pure class I action. Like class Ia drugs, class Ib drugs are use-dependent blockers of voltage-gated Na+ channels (slows upstroke and prolongs refractory period). Unlike class Ia drugs, Ib drugs do NOT prolong phase 2 of AP
Class Ic drug examples
propafenone, flecainide, encainide (probably forget encainide)
Class Ic drug actions
Use-dependent blockers of Na channels, produce most pronounced slowing of upstroke and midly prolongs phase 2 (by blocking K channels), powerful prolongation of tissue refractory period
What is use-dependence?
The block of Na+ channels by class I antiarrhythmic drugs is optimized so that Na+ channels in myocytes with abnormally high firing rates or abnormally depolarized membranes will be blocked to a greater degree than are Na+ channels in normal, healthy myocytes. Also important for class IV Ca channel blockers
Explain the mechanism of use-dependence
The hydrophilic drug can only enter/exit the channel when the channel is open
How do use dependent channel blockers prolong the refractory period?
These drugs block initially by entering the open channel, but they have a higher affinity for the inactivated state of the channel. That means they stabilize the inactivated state, thus prolonging the time the channel spends in the inactivated state
What is another mechanism that some class I drugs use to prolong refractory period?
Class Ia drugs prolong phase 2 and delay repolarization via a class III action (blocks K channels). Prolonged phase 2 means myocyte is depolarized for longer and more Na channels become inactivated, making refractory period longer.
How do Class I drugs suppress re-entrant arrhythmias?
- slowing AP conduction velocity (reducing upstroke rate) 2. Prolonging refractory period
Explain how slowed conduction velocity suppresses re-entry
Reduced upstroke results in slower conduction velocity and a slower AP is more likely to fail to propagate trhough a depressed region. This converts a uni-directional block into a bi-directional block
Explain how prolonging refractory period suppresses re-entry
Refractory tissue will not generate an AP, so re-entry of excitation is prevented
What are examples of Class II drugs?
propranolol, metoprolol, esmolol
Class II drug actions
Beta-adrenergic receptor blockers reduce pacing rate (automaticity) and prolong refractory period in SA/AV nodes by reducing funny current, L-type Ca and Ks current. This reduces rate of diastolic depolarization, reduces upstroke rate, and slowes repolarization in AV node.
What are class II drugs used for?
terminate arrhythmias that involve AV nodal re-entry, and in controlling ventricular rate during atrial fibrillation.
Class III drug examples
ibutilide, dofetilide, amiodarone, sotalol, bretylium
What do class III drugs do?
Block K channels (ibutilide and dofetilide specifically block Kr). This prolongs phase 2 in fast Aps and prolongs the refractory period.
How do class III drugs prolong the refractory period?
Prolonged duration of phase 2 leads to increased inactivation of Na channels
What other actions does amiodarone have (in addition to blocking K channels?)
reduces conduction velocity and increases refractory period by blocking Na+ channels. Also decreases rate of diastolic depolarization (phase 4) in automatic cells, thus reducing firing rate
