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Flashcards in Antiarrhythmic drugs Deck (36):

Action potential phases

-Phase 0: depolarization by inflow of Na
-Phase 1: partial repolarization by outflow of K
-Phase 2: plateau by slow inward Ca
-Phase 3: repolarization by K outflow
-Phase 4: resting potential, but in pacemaker cells there is slow Na influx leading to autorhythmicity
-Refractor period: phases 1-3
-Drugs will target either phase 0 (prolong depolarization) or phase 3 (prolong depolarization)
-Targeting phase 0 means affecting Na permeability
-Targeting phase 2&3 means affecting K permeability (can also target both)


Inhibiting Na permeability

-Slows depolarization (phase 0)
-Slows conduction, decreases slope and magnitude of AP
-Prolongs P wave and QRS


Inhibiting K permeability

-Slows repolarization (extends phase 2 and 3)
-Prolongs AP duration (APD), prolongs refractory period
-Prolongs ST segment


How ventricular APs relate to ECG

-Phase 0 = QRS
-Phase 2 = ST segment
-Phase 3 = T wave
-Refractory period goes until the peak of the T wave (close to the resting potential in the AP)


Summary of drug effects on AP/ECG

-Inhibiting Na influx: prolongs phase 0 and decreases peak, prolongs P wave and QRS complex (get wider)
-Inhibiting K efflux: prolongs phase 2 (and 3) which widens the ST segment
-If you inhibit both K and Na you are prolonging phase 0, 2, and 3 which thus widens the P wave, QRS, and ST segment


Pacemaker cells and latent pacemakers 1

-Normal pacemakers are in the SA node (70/min)
-Latent pacemakers are in other areas like AV node (50/min) or conduction pathways (30/min) or ventricles (10/min)
-Latent pacemakers have slower phase 4 depolarization than SA node, thus are depolarized (controlled) by SA node


Pacemaker cells and latent pacemakers 2

-Ectopic pacemakers occur when the SA node does not fire and a latent pacemaker takes control of the rhythm
-Pacemaker rate is determined by the slope of phase 4 depolarization (larger the slope the greater the rate)
-Injured cardiac tissue can spontaneously depolarize, due to leaky membrane and less negative resting potential
-Can convert a pacemaker to latent pacemaker by slowing down phase 4 depolarization or increasing the threshold


Early afterdepolarization (EAD)

-Positive changes in membrane potential during depolarization
-Occur either in plateau phase (2) or repolarization (3)
-Prolongation of QT interval is big risk factor
-Greater risk when on K inhibitors b/c they prolong ST and thus QT


Torsades des pointes

-Wise QT can lead to ventricular tachycardia (torsades) in which each beat has a different morphology
-The danger is ventricular fibrillation
-Blocking K efflux increases the chance b/c it widens the QT


Delayed afterdepolarization (DAD)

-Ectopic beat (premature contraction) that occurs after repolarization is complete
-Occurs @ greater frequency when myocardium has high concentrations of Ca
-Think digitalis/digoxin (increases Ca)


Altered impulse conduction 1

-Functional: impulse encounters refractory period
-Fixed: impulse encounters area of scar/fibrosis
-Can result in brady or tachyarrhythmias
-Reentry may occur if there is a ring of tissue that does not conduct normally


Altered impulse conduction 2

-Bidirectional block: normal conduction of a ring of tissue, both sides of the ring conduct at equal velocity and cause the two impulses to cancel when they meet (does not form reentrant loop)
-Unidirectional block: when a ring of tissue does not conduct normally and forms a reentrant loop b/c part of it (fibroses areas) is no longer refractory when the retrograde impulse arrives (from the other side)


Converting unidirectional block to bidirectional block

-Prolonging the refractory period by reducing K permeability
-Or slowing depolarization by reducing Na permeability (affects ischemic/infarcted areas predominantly)
-Ectopic pacemakers are more sensitive to anti arrhythmic drugs than SA node


Prolonging refractory period in unidirectional blocks

-Inhibiting K permeability (efflux) will delay repolarization and prolong the refractory period
-When the retrograde impulse meets the ischemic tissue, the tissue will be in refractory period and unable to fire
-This creates a bidirectional block and eliminates the arrhythmia


Decreasing AP peak in unidirectional blocks 1

-Inhibiting Na influx will decrease the peak of phase 0 (depolarization) in ischemic/infarcted tissue (preferentially)
-Ischemic/infarcted tissue has fewer functioning Na channels, thus the resting potential is less negative, the slope of AP is decreased, and the magnitude of the AP is decreased


Decreasing AP peak in unidirectional blocks 2

-Further blocking Na influx results in a greatly reduced depolarization and prevents the damaged area from reaching threshold when the retrograde impulse arrives
-Since the retrograde impulse cannot cause the damaged area to depolarize to threshold (Na channels blocked) the retrograde impulse cannot continue and a unidirectional block is transformed into a bidirectional block


Antiarrhythmic drug (AADs) functions

-Decrease automaticity of ectopic pacemakers more than SA node
-Either decrease excitability/AP magnitude (Na inhibition) or increase refractory period (K inhibition) in more depolarized (ischemic/infarcted) tissue
-Other types of AADs: Ca blockers (nodes use Ca to depolarize, so these will mostly affect AV node arrhythmias), and BBs


Classes of AADs: Ia-c (1)

-Class Ia: blocks Na influx (moderate) and K efflux, thus slows depolarization/conduction (and reduces peak) in atria and ventricles, and prolongs repolarization (refractory) time (APD)
-Widens P, QRS, and ST segment
-Includes Quinidine, procainamide, disopyramide
-Class Ib: blocks Na influx (mild) only, and it shortens AP peak and repolarization time (in normal cells) but prolongs refractory period/APD (repolarization time) in ischemic cells (still inhibits phase 0 depolarization)


Classes of AADs: Ia-c (2)

-Class Ib works only in ischemic areas and only in ventricles, and in these areas has the same effect as class Ia (widens P, QRS, and ST segment)
-Includes lidocaine, mexilitine, tocainide
-Type Ic: blocks Na influx (strong) only, but does not change repolarization time
-Only prolongs phase 0 and lowers AP peak (prolongs P and QRS)
-Includes Fecanide and propafenone


Classes of AADs: II-misc. (1)

-Type II are BBs: diminsh phase 4 depolarization in pacemakers, thus reduce automaticity of ectopic pacemakers
-Type III block K efflux and markedly prolong repolarization time (ST segment)/APD/refractory period
-Works for both ventricular tachycardia and SVTs
-Type III includes amiodarone, sotalol, and ibutilide


Classes of AADs: II-misc. (2)

-Type IV are Ca influx blockers that work on the AV node mostly
-Prolongs depolarization (phase 4) and repolarization time in AV node, thus decreasing conduction time thru AV node
-Works only in SVTs
-Type IV includes verpamil and diltiazem
-Misc: adenosine and digoxin


Similarity btwn class I drugs

-All class I drugs slow depolarization of ectopic pacemaker cells by 2 ways
-They increase the threshold for AP (make threshold potential more positive- harder to reach)
-They also decrease the slope of phase 4 depolarization (increase the time to reach threshold)
-Both accomplished by blocking Na channels


Class Ia drugs 1

-These drugs block Na influx moderately, and K efflux
-They prolong phase 0 (and reduce AP magnitude) and prolong APD/refractory period (widens P, QRS, ST segment)
-All have some degree of vagolytic action (prevent Ach release from vagus)
-Quinidine: effective for atrial and ventricular arrhythmias, not used much due to side effects (toxic)


Class Ia drugs 2

-Most common negative side effects (NSE) of quinidine: GI disturbances (anorexia, nausea, vomiting, etc) and cinchonism (syndrome of headaches, tinnitus, dizziness)
-Increases risk of torsades de pointes (almost all AADs do this) b/c it increases ST segment (and thus QT interval)


Class Ia drugs 3

-Procainamide: Effective mostly for ventricular arrhythmias, also avoided due to toxic side effects
-NSEs of procainamide: lupus-like syndrome and tosades are most important
-Disopyramide: approved only for ventricular arrhythmias, but avoided due to NSEs
-NSEs: depression of cardiac conduction can precipitate heart failure, also torsades


Class Ib drugs 1

-On normal cells these drugs shorten APD (repolarization) and prolong depolarization (also decrease AP peak)
-But these effects are not significant b/c these drugs only work on ischemic/infarcted tissue and in the ventricles
-In infarcted tissues Ib drugs have the same action as class Ia drugs: decrease AP peak and prolong depolarization, and prolong repolarization/APD (widen P, QRS, ST segment)
-Lidocaine: effective for acute ventricular arrhythmias during acute MI (no effect in atria)


Class Ib drugs 2

-Lidocaine is rapidly redistributed to peripheral tissues, and undergoes extensive 1st pass metabolism (cannot be taken orally)
-Reduced liver flow (HF) will increase serum concentrations
-Serum levels must be monitored, toxicity (neurologic) depends on serum levels, and routine use is contraindicated
-Other type Ib drugs (tocainide, mexiletine) are similar to lidocaine but are resistant to 1st pass metabolism and thus can be administered orally


Class Ic drugs 1

-Powerful inhibitors of Na influx, they greatly slow phase 0 depolarization and lower AP peak, w/o affecting repolarization/APD
-Prolong only P and QRS
-Flecainide: only approved for use of supra ventricular arrhythmias in normal hearts
-Is pro arrhythmic in setting of structural heart disease and ventricular arrhythmias


Class Ic drugs 2

-Flecainide is used in WPWS, since flecainide preferentially blocks conduction thru accessory pathways in setting of tachyarrhythmias
-Other adverse effects of flecainide: CNS (blurred vision, nausea, tremor, metallic taste), heart failure
-Propafenon: similar indications to flecainide (supra ventricular arrhtyhmias)
-Adverse effects: metallic taste, constipation, proarrhtyhmic


Class II drugs

-BBs, diminish phase 4 depolarization in nodes and decrease ectopic pacemaker depolarization
-Prolong AV conduction, decrease HR and contraction force
-Used in SVAs and ventricular ectopy, also prevent sudden cardiac death in acute MI
-Adverse effects: fatigue, lethargy, hyperglycemia, hypotension, bradycardia


Class III drugs 1

-Prolong APD by inhibiting K efflux, no change on phase 0
-Prolongs ST segment, APD, refractory period
-Amiodarone: widely used for atrial and ventricular arrhythmias
-Low toxicity (less risk of torsades), but slow hepatic metabolism and inhibits CYP450


Class III drugs 2

-NSEs of amiodarone: dose-dependent toxicity of pulmonary fibrosis, hyper or hypothyroidism, and hepatocellular necrosis
-Therefore need to have baseline PFT (pulm function tests), TFT (thyroid function test), and LFT (liver function test)
-Dronedarone: less toxic than amiodarone, so better for long-term use, but can increase mortality in those w/ HF


Class III drugs 3

-Dofetilide: oral only, used during Afib, but can lead to excessive QT prolongation and thus increases risk for torsades
-Ibutilide: IV only, otherwise same as dofetilide (contraindicated in those w/ LVH)
-Sotalol: oral only, used for atrial and ventricular arrhythmias, less QT prolongation so less risk of torsades


Class IV drugs

-Ca channel blockers (verapamil and diltiazem)
-They prolong AV nodal conduction and refractory time
-Decrease HR and contractility
-Only are affective in SVAs (no ventricular arrhythmia use)
-NSEs: contraindicated in those w/ LV dysfxn (HF)



-Binds to receptor and inhibits AC, thus inhibits the inward Ca current
-Since AV node utilizes Ca for depolarization adenosine slows conduction thru AV node and inhibits AV node reentry arrhythmias
-NSEs: flushing, dyspnea, chest pain, transient arrhythmias
-Contraindicated in asthma, heart block



-Cardiac glycoside, blocks Na/K ATPase
-This increase Na levels and in turn leads to deactivation of Na/Ca channel (brings Na in for Ca out)
-As Na levels rise there is less of a gradient for Na to enter via the Na/Ca channel so more Ca remains in the cell
-Digoxin increase cardiac contraction and slows AV conduction by increasing AV node refractory period
-Used in control of ventricular rate during Afib or atrial flutter
-Improves Sx from CHF exacerbations
-Narrow therapeutic index