CVS Physiology and Antiarrhythmics Flashcards
(112 cards)
1
Q
describe the P wave
A
Atrial depolarization
[Initiation - phase 4 Ih channels / phase 0 Ca++ channels in SA node]
2
Q
describe the PR interval
A
Conduction time thru AV node [Phase 0 Ca++ channels in AV node]
-beginning of P to beginning of QRS
3
Q
describe the QRS interval
A
Ventricular depolarization-conduction thru His-Purkinje [Phase 0 Na+ channels]
4
Q
describe the QT interval
A
Action potential duration [phase 2-3 K+ channels]
-beginning of QRS to end of T wave
5
Q
describe the T wave
A
Ventricular repolarization
6
Q
The targets for antiarrhythmic drugs and the basis for their current classification scheme are ____
A
the ion channels that underlie the cardiac action potential.
7
Q
Describe the phases of the ionic basis of slow response
A
(cells in SA node, AV node)
Phase 4: Results from gradual increase of depolarizing current (If: Na+ and Ca++ [T-type]) and a gradual decrease in repolarizing potassium current (IK1) during diastole.
Phase 0: Slow upstroke carried by L-type Ca++ current (ICa).
Phase 3: Repolarization, activation of K+ channels (IK) and inactivation of L-type Ca++.
8
Q
Describe the phases of the ionic basis of fast response
A
PHASE 0: Stable membrane potential until external depolarization opens membrane channels with rapid inward movement of Na+ ions.
PHASE 2: Slow inward movement of Ca++ ions [ICa] balanced by outward movement of K+ ions [IKr] leads to plateau (prolonged) phase of depolarization. The L-type Ca++ current is coupled to cardiomyocyte contraction.
PHASE 3: Ca++ channel inactivation occurs slowly with gradual increase of K+ permeability leading to final repolarization which allows return of Na+ channels from inactivated to resting state (now able to activate in response to action potential).
PHASE 4: Return to resting potential, outward K+ current is sufficient to maintain relatively stable negative resting potential. [Na+ pump and Na+/Ca++ exchanger maintain ionic steady state]
9
Q
Property of automaticity (impulse initiation) is influenced by:
A
slope of phase 4 depolarization, resting Em, and threshold potential
10
Q
The autonomic nervous system (β1-adrenergic and M2-muscarinic receptors) affects the properties of automaticity via
A
- regulation of ion channels that include Ca++ (phase 0),
- K+ (phase 3), and
- the Na+/Ca++ channels of phase 4 (If)
11
Q
What phase of ionic basis?
Stable membrane potential until external depolarization opens membrane channels with rapid inward movement of Na+ ions.
A
phase 0
fast
12
Q
What phase of ionic basis?
: Return to resting potential, outward K+ current is sufficient to maintain relatively stable negative resting potential. [Na+ pump and Na+/Ca++ exchanger maintain ionic steady state]
A
phase 4
fast
13
Q
What phase of ionic basis?
Slow inward movement of Ca++ ions [ICa] balanced by outward movement of K+ ions [IKr] leads to plateau (prolonged) phase of depolarization. The L-type Ca++ current is coupled to cardiomyocyte contraction.
A
phase 2
fast
14
Q
What phase of ionic basis?
Ca++ channel inactivation occurs slowly with gradual increase of K+ permeability leading to final repolarization which allows return of Na+ channels from inactivated to resting state (now able to activate in response to action potential).
A
phase 3
fast
15
Q
what is automaticity
A
Automaticity is the ability of certain cardiac cells to alter resting membrane potential to excitation threshold WITHOUT external stimulus (slow spontaneous depolarization occurs during phase 4).
16
Q
___ possesses highest intrinsic automaticity and serves as normal pacemaker of heart for impulse initiation.
A
SA node
17
Q
What displays automaticity (they are latent pacemakers that can become dominant under certain conditions when the SA node is damaged)
A
- SA node (tissue w/ greatest automaticity)
- specialized atrial muscle fibers
- AV nodal cells (50-60bpm)
- His Purkinje cells (30-40bpm)
18
Q
Impulse conduction throughout most of the heart occurs due to ___ resulting from ___. The exception is ________
A
membrane depolarization
opening of sodium channels (phase 0, fast response)
The exception is conduction through the AV node which results from the opening of calcium channels (phase 0, slow response
19
Q
describe impulse conduction from the SA node through the atrial muscle
A
- Electrical impulses are normally initiated in the SA node, the tissue with greatest automaticity (phase 4 spontaneous depolarization) and spreads like wave through atrial muscle cells (phase 0 Na+ current).
- The atrium contracts [P wave on EKG] and the impulse reaches AV node
- [PR interval on EKG is measure of conduction time from atrium thru AV node].
20
Q
describe the impulse conduction through the AV node
A
Acts as gate, allows ventricles to fill completely prior to contractions and prevents excessive impulses from reaching ventricles. Nodal cells are slow response cells and phase 0 current is carried by Ca++ ions. AV node can spontaneously depolarize if SA node damaged (known as nodal rhythm of 40-60 bpm).
21
Q
Describe the impulse conduction through the His-Purkinje System through Ventricular muscle
A
- Impulse reaches terminal portion of electrical system of Purkinje fibers. Spreads like wave through ventricular muscle to cause contractions
- [QRS duration on EKG indicates time required for activation of all ventricular cells] giving rise to heartbeat or pulse wave. - Ventricular repolarization then occurs
- [T wave on EKG] as diastole begins [QT interval on EKG reflects duration of ventricular action potential]
22
Q
During phase 0 of the ventricular action potential, sodium channels in the ___ state ___ to depolarize the cell
A
resting
open-activate
23
Q
What is the primary determinant of conduction velocity?
A
the magnitude of the phase 0 depolarizing Na+ current that is the primary determinant of conduction velocity
24
Q
The channels are then inactivated and no longer permit sodium entry during phases ____
A
1, 2, and 3
25
Channels must return to the ___ state before they can open-activate again during the next action potential
resting state (phase 4)
26
Transitions between the states of the Na+ channel are dependent on ___
membrane potential and time
```
M= activation gate
H= inactivation gate
```
27
Magnitude of depolarizing current is influenced by:
1. Rate of phase 0 depolarization → greater rate, greater conduction velocity (related to number of sodium channels in resting state and able to open following depolarization)
2. Membrane potential (Em)
3. effective refractory period (ERP)
4. AP duration (APD)
28
Class I antiarrhythmic drugs that block phase 0 Na+ channels will have what effect?
slow the rate of depolarization and slow conduction velocity
29
Less negative resting potential (from ischemic tissue damage) results in a ___ number of inactivated fast sodium channels and a ___ conduction velocity (contributes to conduction abnormalities --> arrhythmias)
greater
reduced
30
how does membrane potential influence the magnitude of depolarizing current?
-affects number of channels in resting state available to open. At less negative resting membrane potentials [-75 to -55 mV]), resting Na+ channels begin to inactivate and fewer are available (resting) to contribute to the rate of phase 0 depolarization.
31
conduction velocity is ____ by sub-threshold depolarization of resting membrane potential.
slowed
32
__, __, and ___ are common causes of depolarization (by __) all of which can result in impaired conduction with arrhythmogenic potential
Injury to cell, ischemia, or excessive stretch
increasing membrane potential (Em)
33
How does effective refractory period (ERP) influence the magnitude of depolarizing current?
reflects the time for sufficient sodium channels to return from the inactivated state to the resting state to support a subsequent action potential.
34
How does action potential duration (APD) influence the magnitude of depolarizing current?
- reflects the return of the Em to the diastolic resting membrane potential (-80-90 mV).
- An increase in APD, by sustaining a depolarized Em and slowing Na+ channel recovery, will increase the effective refractory period and impair impulse conduction.
35
An increase in APD, by sustaining a depolarized Em and slowing Na+ channel recovery, will have what effect on ERP and conduction
increase the effective refractory period and impair impulse conduction
36
Class III antiarrhythmic agents that block phase 3 K+ channels will have what effect on Em, APD, and conduction
sustain a depolarized Em, increase APD, and impair conduction
37
Describe Class I antiarrhythmics
1. ALL members block sodium channels and affect phase 0 of fast response cells (major) and phase 4 of slow response cells (minor).
2. They will slow or block conduction (especially in depolarized cells) and slow or abolish abnormal pacemakers.
3. The subclasses will differ in their effects on K+ channels which are reflected by differing effects on the action potential and EKG.
38
What are Class Ia antiarrhythmics
- Quinidine (Quinaglute®),
- Procainamide (Procan®),
- Disopyramide (Norpace®)
39
Describe Class Ia antiarrhythmics
*blocks Na+ channels and blocks K+ channels to prolong refractory period
1. Moderate Na+ channel blockade with K+ channel blockade
2. Repolarization delayed, wide action potential, prolongs QRS and QT interval
40
What are examples of Class Ib antiarrhythmic drugs
- Lidocaine (Xylocaine®),
| - Phenytoin (Dilantin®)
41
Describe Class Ib antiarrhythmic drugs
1. Mild Na+ channel blockade without K+ channel blockade - little effect on normal tissue
2. Repolarization is accelerated - stabilizes inactivated state of Na+ channel
3. Effective for VENTRICULAR arrhythmias associated with depolarization (ischemia, digoxin toxicity), but NOT effective for arrhythmias in normally polarized tissues (atrial fibrillation or flutter)
*Minimal effect on atrial tissues or AV conduction
42
What are example of Class Ic antiarrhythmic drugs
- Flecainide,
| - Propafenone (Rhythmol®)
43
Describe Class Ic antiarrhythmic drugs
1. Marked Na+ channel blockade without K+ channel blockade
2. Marked inhibition of His-purkinje tissue and QRS prolongation
3. Can be very pro-arrhythmic**
44
What are examples of Class III antiarrhythmics
- Amiodarone (Cordarone®) –
- Dronedarone (Multaq®),
- Sotalol (Betapace®),
- Ibutilide (Corvert®),
- Dofetilide (Tikosyn®)
45
Describe Class III antiarrhythmics
1. Block K+ channels to delay phase 2-3 repolarization current (Kr) and increase refractory period and APD
2. Reduces ability of the heart to respond to rapid tachycardias. Phase 4 diastolic current is not affected by this class, in contrast to Class I.
46
Amiodarone also has Class __ properties
IA
| Na+ channel blockade
47
What are examples of Class II antiarrhythmic drugs
- Metoprolol (Lopressor®),
| - Esmolol (Brevibloc®)
48
Describe class II antiarrhythmics
*Beta-blockers that suppress abnormal pacemakers and slow AV conduction
1. Block β1 adrenergic receptors - slows phase 4 depolarization and phase 0 AV nodal conduction
2. Suppresses abnormal pacemakers and AV nodal reentrant arrhythmias
3. Reduction of both Na+ and Ca++ current during diastole [phase 4]
49
What are examples of Class IV antiarrhythmic drugs
- Verapamil (Calan®, Isoptin®),
| - Diltiazem (Cardizem®)
50
Describe Class IV antiarrhythmics
*Ca++ channel blockers (AV node) that prolong AV conduction - slow heart rate
1. Ca++ channel blockers - both activated and inactivated Ca++ channels will be blocked
2. Effect will be greater in tissues that fire frequently, are more depolarized at rest, and are dependent exclusively on the Ca++ current for activation
3. Greater effects on the AV and SA nodes to slow phase 0 to prolong AV conduction and ERP
51
describe how Adenosine (Adenocard) works
Endogenous nucleoside that interacts with P1 (purinergic) receptors to suppress nodal action potentials by hyperpolarizing this tissue (increase in K1 current) and by reducing Ca++ current resulting in inhibition of AV nodal conduction and increased refractory period.
52
Describe how Digoxin (Lanoxin) works
Possesses cardiac parasympathomimetic actions (vagal activation, acetylcholine-like as above) that can be used to treat rapid atrial or AV nodal arrhythmias
53
Electrophysiological effects in heart can seem paradoxical as alterations in serum K+ can change both ____ and ___ independently. Effect on conductance often predominates with ectopic pacemaker cells more sensitive than cells in SA node.
electrochemical gradient
potassium conductance
54
How does hypokalemia affect conductance
↓ extracellular K+ decreases conductance (despite ↑ electrochemical gradient)
55
Hypokalemia is associated with ___ incidence
| of arrhythmias
an increased
56
Suppresses ectopic pacemakers
potassium-ion
57
Hyperkalemia ___ conduction and can cause
| ____
depresses
reentrant arrhythmias
*critical to normalize K+ levels
58
Used to treat rapid atrial or AV nodal arrhythmias
Digoxin
59
Effective in digoxin-induced arrhythmias torsade de
| pointes arrhythmias
Magnesium
60
how does hypokalemia and hyperkalemia appear on EKG
hypo: prominent U waves
hyper: peaked T waves
61
Why does hypokalemia predispose you for digoxin toxicity
digoxin and K+ competes for binding to same site on Na+-K+-ATPase plus ↑ abnormal cardiac automaticity
62
how does hyper and hypo-kalemia affect APD
hypo: prolonged APD
hyper: reduced APD---> Increased incidence of bradycardia and conduction disturbance → heart block
63
arrhythmias occur because of ___ or ___ that then result in rates that are either too slow or too fast.
disturbances in impulse initiation OR impulse conduction
64
What is SA node dysfunction?
1. bradyarrhythmia due to abnormal impulse initiation (failure to initiate)
2. Result of normal aging process or underlying pathology in sinus node myocytes such as infiltrative cardiomyopathy or heart failure
65
What is the treatment of SA node dysfunction (bradyarrhythmia due to abnormal impulse initiation)
1. Very limited role for medications – if patient symptomatic a pacemaker can be useful
2. Withdraw potentially causative agents such as beta blockers or calcium channel blockers
66
What is AV block
1. Bradyarrhythmia due to abnormal impulse condition (failure to conduct)
2. can result from disease in AV node or below AV node (His Purkinje system)
67
Describe 1st degree AV block
Increase in PR interval, usually not of clinical concern
68
Describe the 2nd degree AV blocks
*Incomplete block with 2 varieties
Mobitz I: Progressive prolongation of PR interval on EKG until blocked beat
Mobitz II: Usually results from disease in His-Purkinje system with block of conduction being more unpredictable (some atrial depolarizations will conduct) and requires urgent treatment to prevent asystole
69
Describe 3rd degree AV block
(complete heart block): No association between atrial depolarizations and ventricular depolarizations. Escape rhythms from AV junction (35-45 bpm) or His-Purkinje system (15-30 bpm) are often symptomatic
70
What is the treatment for acute and chronic AV block
acute: Chronotropic agents (increase rate of phase 4 depolarization at SA and AV node) can be useful temporarily for potentially reversible causes – atropine, dopamine, epinephrine
chronic: permanent pacemaker
71
What is sinus tachycardia
1. (SA node firing rate of 100-180) is not an arrhythmia itself but can be an abnormal finding.
2. While it can be a normal physiologic response (e.g., during exercise), it is often a manifestation of an important underlying pathologic condition (poor pain control, volume depletion, anemia, bacteremia or sepsis, or hypoxia and hypercarbia).
72
Treatment of sinus tachycardia
reverse underlying condition
73
describe the 2 types of triggered automaticity tachycardias
1. early afterdepolarization--Most common when heart rate slow, extracellular K+ is low, and with drugs that prolong APD
2. Late (delayed) afterdepolarizations-- Occur shortly after repol but before the next normal depol. Seen with intracellular Ca++ overload (MI, ischemia, adrenergic stress [increased heart rate, e.g., stress or use of adrenergic agonists], digoxin toxicity). Mechanism uncertain, but it appears that intracellular Ca++ accumulation activates the Na+/Ca++ exchanger and the electrogenic influx of 3 Na+ for 1 Ca++ depolarizes the cell
74
early afterdepolarization triggered automaticity tachycardia is seen with:
1. decreased HR
2. low extracellular K+
3. drugs that prolong APD/QT
75
late afterdepolarization triggered automaticity tachycardia is seen with:
1. intracellular Ca2+ overload seen with
2. ischemia
3. adrenergic stress (increased HR and epi)
7. digoxin toxicity
76
what does atrial tachycardia result from?
an abnormal focus of atrial tissue with its own automaticity and ability to generate atrial beats.
77
causes of AT
often in the setting of a trigger
1. catecholamine surge
2. caffeine
3. heart failure
78
treatment of AT
1. Beta-blockers, calcium channel blockers, Class I and III agents (30% success at 1 year)
2. Ablation (controlled lesion) has success rates between 70-90%
79
Tachyarrhythmias due to Abnormal Impulse Conduction
1. Reentry (most common mechanism, over 85%)
2. SVT-- AV node reentry
3. Afib
4. Atrial flutter
5. VT
6. VF
7. Torsades de Pointes
80
Single impulse excites areas of heart myocardium more than once, resulting in an abnormally rapid rate.
Reentry tachycardia
81
• Characterized by retrograde conduction of an impulse into previously depolarized tissue. It is usually caused by the presence of a unidirectional conduction block in a bifurcating conduction pathway (characteristic of damaged tissue that allows current to move in one direction only).
Reentry tachycardia
82
For reentry to occur, the time through the retrograde pathway must exceed the ____. This can occur in atrial, nodal, or ventricular tissue.
refractory period of the reentered tissue
83
Describe what SVT is
A premature atrial depolarization arrives at AV node and conducts through pathway α to ventricle, but finds pathway β is still refractory.
- Conduction can occur in the retrograde direction of pathway β (longer pathway so tissue no longer refractory) leading to reentry into atrial tissue and results in tachycardia.
84
Acute treatments of SVT
1. Adenosine (often in escalating doses) produces transient AV nodal blockade and almost always terminates the arrhythmia
2. Other AV nodal blockers (beta-blockers and calcium channel blockers) usually only slow the rate
3. Vagal maneuvers (carotid sinus massage, bearing down of abdominal muscles, cold water immersion) release acetylcholine at the AV node and may terminate arrhythmia
85
Chronic treatments of SVT
1. Very infrequent episodes → vagal maneuvers can be helpful
2. More frequent episodes → daily AV nodal blockers (50% success)
3. Frequent symptoms but fail, can’t tolerate, or won’t take medications → catheter ablation (95-98% success)
86
what are AV nodal blocking agents
Beta blockers
| Calcium channel blockers
87
Describe what atrial flutter is
Prototypical reentrant arrhythmia involving unidirectional electrical conduction around the tricuspid valve utilizing an area of slow conduction (i.e., a critical isthmus between two electrically unexcitable structures such as myocardial scars, valves, veins, etc.).
88
treatment of atrial flutter
1. Pharmacologic treatment with AV nodal blockers (control rate) or Class I or Class III agents (minimize premature beats) – long-term success < 50%
2. Electrical cardioversion initially successful but high recurrence rate (50% in a year)
3. Radio frequency ablation of arrhythmia – long-term success rate 93-98%
89
describe what Afib is
Due to chaotic electrical activity in atria with multiple microreentrant wavelets existing simultaneously. Often a trigger exists that initiates the tachycardia and the underlying substrate to maintain the arrhythmia.
90
What is the treatment of Afib?
* Rate Control – Rhythm Control - Anticoagulation
2. Rate control with AV nodal blockers
2. Rhythm control:
- Pharmacologic treatment with Class I and III agents
- Cardioversion successful acutely
- Ablation – some success but risk precludes use as first line treatment
3. Anticoagulation – risk stratification via CHADS2 score for use of low dose aspirin or warfarin-dabigatran
91
Usually a dangerous and often life threatening arrhythmia. Relies entirely on ventricular tissue for arrhythmia origin and propagation. Mechanisms involve either a reentrant arrhythmia (90%) involving a prior myocardial scar or an automatic or triggered focus (10%).
VT
92
acute tx of VT
1. Amiodarone if patient awake and not hypotensive
| 2. Cardioversion if patient not hemodynamically stable
93
chronic tx of VT
1. Some success with pharmacologic agents
2. Ablation is 90% curative
3. Implantable cardioverter defibrillator (ICD) if structural heart disease present - more effective than drugs in long-term suppression of arrhythmias, but amiodarone or sotalol used in conjunction can reduce number of ICD shocks needed for NSR.
94
Tx of VF
1. Electrical defibrillation, followed by
2. epinephrine (or vasopressin) and
3. amiodarone if not controlled,
4. followed by continued attempts at defibrillation
95
predisposing factors of Torsades de Pointe
1. prolonged QT interval
2. hypokalemia
3. slowed HR
96
tx of torsades de pointe
1. Correction of electrolyte abnormalities (potassium chloride for hypokalemia) and
2. magnesium sulfate
97
What are the Major Actions of Antiarrhythmic Agents for Tachyarrhythmias
1. Rhythm control--Modify impaired conduction at any site via interruption of reentrant rhythm or production of bidirectional block
2. Rate control-- Block conduction at AV node via multiple mechanisms [collectively described as AV nodal blocking drugs]
98
Rhythm Control of tachyarrhythmias: Modify impaired conduction at any site via interruption of reentrant rhythm or production of bidirectional block by:
1. Prolongation of phase 2 via block of K+ channel that maintains a depolarized Em and delays recovery of Na+ channels resulting in an increased ERP [Class III, Class IA]
2. Increase in conduction time (decrease conduction velocity): Block of phase 0 Na+ channel current, the major determinant of conduction [Class I, Class III amiodarone]
99
Rate Control of tachyarrhythmias: Block conduction at AV node via multiple mechanisms [collectively described as AV nodal blocking drugs]:
1. Block Ih and L-type Ca++ current to prolong repolarization and increase ERP [Class II, Class IV]
2. Parasympathomimetic action to slow conduction at AV node [digoxin]
3. Activation of IK in nodal tissue producing membrane hyperpolarization and decreased phase 4 slope and block of Ih and L-type Ca++ current to prolong repolarization and increase ERP [adenosine]
100
How is procainamide given
orally and parenterally
101
how is lidocaine given
parenterally only
| *large 1st pass effect
102
how is flecainide and profafenone given
orally both
| *propafenone has a high 1st pass effect
103
how is propranolol and esmolol given
propranolol: orally or IV
esmolol: IV only
104
how is amiodarone, Ibutilide, and Dofetilide given?
amiodarone- orally-- long half life
Ibutilide- IV
Dofetilide- orally
105
how is verapamil and adenosine given
verapamil- oral/IV
| adenosine- IV
106
SE of procainamide
1. lupus syndrome
| 2. N/diarrhea
107
SE of Quinidine
1. diarrhea/cramping
| 2. LH
108
SE of lidocaine
1. least cardiotoxic agent
| 2. neurological SE (tremors, seizures, LH, confusion, paresthesias)
109
SE of Flecainide / Propafenone
Overall better tolerated than other class I
1. can be pro-arrhythmic
2. CNS effects
110
SE of amiodarone
1. bradycardia or heart block
| 2. thyroid dysfunction
111
SE of verapamil
1. dose related negative inotropic effect
112
SE of adenosine
1. flushing
| 2. CP/SOB
