Antiarrhythmic drugs Flashcards
1
Q
Action potential phases
A
- 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)
2
Q
Inhibiting Na permeability
A
- Slows depolarization (phase 0)
- Slows conduction, decreases slope and magnitude of AP
- Prolongs P wave and QRS
3
Q
Inhibiting K permeability
A
- Slows repolarization (extends phase 2 and 3)
- Prolongs AP duration (APD), prolongs refractory period
- Prolongs ST segment
4
Q
How ventricular APs relate to ECG
A
- 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)
5
Q
Summary of drug effects on AP/ECG
A
- 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
6
Q
Pacemaker cells and latent pacemakers 1
A
- 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
7
Q
Pacemaker cells and latent pacemakers 2
A
- 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
8
Q
Early afterdepolarization (EAD)
A
- 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
9
Q
Torsades des pointes
A
- 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
10
Q
Delayed afterdepolarization (DAD)
A
- 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)
11
Q
Altered impulse conduction 1
A
- 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
12
Q
Altered impulse conduction 2
A
- 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)
13
Q
Converting unidirectional block to bidirectional block
A
- 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
14
Q
Prolonging refractory period in unidirectional blocks
A
- 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
15
Q
Decreasing AP peak in unidirectional blocks 1
A
- 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
16
Q
Decreasing AP peak in unidirectional blocks 2
A
- 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
17
Q
Antiarrhythmic drug (AADs) functions
A
- 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
18
Q
Classes of AADs: Ia-c (1)
A
- 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)
19
Q
Classes of AADs: Ia-c (2)
A
- 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
20
Q
Classes of AADs: II-misc. (1)
A
- 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
21
Q
Classes of AADs: II-misc. (2)
A
- 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
22
Q
Similarity btwn class I drugs
A
- 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
23
Q
Class Ia drugs 1
A
- 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)
24
Q
Class Ia drugs 2
A
- 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)
25
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
26
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)
27
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
28
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
29
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
30
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
31
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
32
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
33
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
34
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)
35
Adenosine
- 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
36
Digoxin
- 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
