6 - Antiarrhythmic Drugs Flashcards
(135 cards)
1
Q
What are predisposing factors for arrhythmias?
A
- Px treated w/ digitalis for heart failure
- Anesthetized px
- Px w/ myocardial infarction
- Anti-arrhythmic drugs
2
Q
What is normally the pacemaker of the heart?
A
SA node
3
Q
Where are conduction fibres?
A
AV node
4
Q
What is an arrhythmia?
A
Any rhythm that is not a normal sinus rhythm w/ normal AV conduction
5
Q
The SA node spontaneously discharges ______ beats per minute
A
60-100
6
Q
What can change the rate of the SA node?
A
Nerves innervating the heart
7
Q
What is the function of the AV node?
A
- Electrical connection btwn atria and ventricles
- Delays action potential by 0.1 second to allow atria to contract and ventricles to fill
8
Q
AV node spontaneously discharges _____ beats per min
A
40-60
9
Q
What is the function of conduction fibres?
A
To excite ventricular mass as near simultaneously as possible
10
Q
Purkinje fibres spontaneously discharge _____ beats per min
A
20-40
11
Q
What is the path of an action potential in the heart?
A
SA node pacemaker -> conduction to atria -> AV -> bundle of His and Purkinje fibres -> ventricular myocardium -> contraction
12
Q
What is the P wave?
A
Atrial depolarization
13
Q
What is the QRS complex?
A
Ventricular depolarization
14
Q
What is the T wave?
A
Ventricular repolarization
15
Q
What is the PR interval?
A
Conduction time from atria to ventricles
16
Q
What is the QRS interval?
A
Time for all ventricular cells to be activated
17
Q
What is the QT interval?
A
Duration of ventricular action potential
18
Q
What causes the differences btwn action potentials?
A
Different ion channels expressed in myocytes
19
Q
Which anti-arrhythmic drugs block Na channels?
A
- Procainamide
- Lidocaine
- Flecanide
20
Q
Which anti-arrhythmic drugs block beta-adrenergic receptors?
A
- Propranolol
- Metoprolol
- Esmolol
21
Q
Which anti-arrhythmic drugs block K channels?
A
- Amiodarone
- Sotalol
22
Q
Which anti-arrhythmic drug blocks Ca channels?
A
Verapamil
23
Q
Which anti-arrhythmic drugs work via other mechanisms?
A
- Magnesium
- Adenosine
- Digoxin
24
Q
What occurs during each phase of an action potential from non-pacemaker cells?
A
0 = Na+ influx 1 = Cl- influx 2 = Ca2+ influx and K+ efflux 3 = K+ efflux 4 = K+ efflux
25
Is the resting potential more negative in pacemaker cells or non-pacemaker cells?
Non-pacemaker cells
26
What happens when the threshold is reached in non-pacemaker cells?
"Active" voltage gated Na channels open, causing rapid depolarization
27
What happens if all Na channels are in the "inactive" state?
Myocyte can't depolarize, so is in an absolute refractory period
28
What if some Na channels are in the "inactive" state?
Myocyte may depolarize, but a less rapid depolarization; called relative refractory period
29
What does rapid depolarization of a cell result in?
Strong and rapid transmission of the impulse to surrounding fibres
30
What does rapid depolarization of the resting membrane potential of a cell cause?
- Decreased # of sodium channels available
- Decrease rate of depolarization
- Decreased strength and speed of impulse
31
What can cause slow depolarization of resting membrane potential?
- Hyperkalemia
- Ischemia
- Drugs blocking sodium channels
32
Sufficient sodium channels must be _____ to allow an action potential to be evoked
Activated
33
What occurs during the funny current in pacemaker cells?
Increased Na+ influx
34
What happens when the threshold is reached in pacemaker cells?
Voltage gated L-type Ca channels open, causing rapid depolarization
35
What happens in phase 3 of an action potential in pacemaker cells?
Voltage gated K channels open and membrane repolarizes
36
Where do fast response times occur in the heart? What is the resting membrane potential of these cells? Do they send off automatic signals?
- Atria, purkinje fibers, ventricles
- -80 to -95 mV
- Purkinje fibers can send off automatic signals; atria and ventricles can't
37
Where do slow response times occur in the heart? What is the resting membrane potential of these cells? Do they send off automatic signals?
- SA node, AV node
- -40 to -65 mV
- Yes, send off automatic signals
38
What is the phase 0 current for non-pacemaker and pacemaker cells?
- Non-pacemaker = sodium
| - Pacemaker = calcium
39
What are arrhythmias related to?
Abnormal pacemaker/conduction and/or muscle depolarization
40
Arrhythmias must be _____ in order to be treated
Symptomatic
41
What are bradyarrhythmias?
HR less than 50-60 bpm
42
How are bradyarrhythmias treated?
W/ pacemaker, not normally w/ drugs
43
What can cause bradyarrhythmias?
- Sick sinus syndrome
| - Atrio-ventricular conduction block
44
What are tachyarrhythmias?
HR over 100 bpm
45
What is a paroxysmal tachycardia?
- HR between 150 and 250 bpm
| - Paroxysm = rapid onset
46
What is an atrial flutter?
Atria beat at 250-350 bpm, but regular heart rhythm
47
What is atrial fibrillation?
Atria beat up to 500 bpm, irregular rhythm, and uncoordinated contraction
48
What is ventricular fibrillation?
- Irregular rhythm w/ uncoordinated contraction
| - Immediate cause of death
49
What is torsade de pointes?
Long QT syndrome
50
What can cause torsade de pointes?
- Genetics
| - Drug induced
51
What are causes of an arrhythmia?
- Insufficient oxygen to myocardial cells
- Acidosis or accumulation of waste products
- Electrolyte disturbances
- Structural damage of conduction pathway
- Drugs (ex: antipsychotics, antihistamines)
52
What are the most important ions for an action potential in pacemaker cells?
Calcium and potassium
53
What are the most important ions for an action potential in non-pacemaker cells?
Sodium, calcium, and potassium
54
What can cause abnormal automaticity of the heart?
- Altered regular pacemaker activity in SA node
| - Pacemaker of abnormal origin (ectopic foci)
55
What can cause abnormal impulse formation?
1) Abnormal automaticity
| 2) Triggered activity
56
What is triggered activity?
Slow and poorly conducted action potential in atria or ventricles
57
What can cause abnormal conduction?
- Impaired AV node (causes bradyarrhythmias)
| - Re-entry/circus conduction (causes tachyarrhythmias)
58
What does enhanced activity of spontaneous pacemakers (AV node, Purkinje fibers) cause?
- Decrease in phase 4 K conductance => increased spontaneous depolarization
- Inactivation of Na+ channels in depolarized cells => converts fast cells to ectopic pacemakers
- Localized supersensitivity to catecholamines following ischemia
59
What is the relationship btwn rate of depolarization and heart rate?
Direct relationship (increase in rate of depolarization causes increased HR)
60
What is the relationship btwn resting membrane potential and heart rate?
More depolarized RMP = increased HR; more hyperpolarized RMP = decreased HR)
61
What is the relationship btwn AP threshold potential and heart rate?
More negative threshold = increased heart rate; more positive threshold = decreased HR (inverse relationship?)
62
What releases acetylcholine and what does it act on?
- Released from para nerves
- Acts on muscarinic receptors; phase 4, so slows depolarization rate, decreases automaticity in SA node, and slows conduction in AV node
63
What releases norepinephrine and what does it act on?
- Released from symp nerves
- Acts on beta receptors; phase 4, so increases depolarization rate and reduces AP firing threshold, increases automaticity in SA node, and increases conduction in AV node
64
What determines how calcium and sodium channels can be depolarized again?
- Sodium channels must be switched from inactive to resting through repolarization
- Calcium channels are based on time
65
What do class 1 and class 3 antiarrhythmic drugs do?
Block potassium channels
66
What can cause calcium channels to be ready before sodium channels?
Prolonged action potential duration (QT interval)
67
What can early afterdepolarization (EAD) trigger?
Torsade de pointes
68
What do torsade de pointes show up as on ECG?
- Twisting of isoelectric points
| - Prolonged QT interval
69
What can torsade de pointes cause?
- Ventricular fibrillation
| - Sudden death
70
What is the tx for torsade de pointes?
Magnesium
71
Which drugs can cause an increased QT interval?
- Antiarrhythmics (class 1a and 3)
- Antihistamines
- Anti-psychotics
- Antibiotics
72
What is required for reentry (circus conduction) to occur?
- Available circuit (closed conduction loop)
- Unidirectional block
- Different conduction speed in limbs of circuit (conduction time > effective refractory period)
73
What are some causes of circus conduction?
- Ischemia
- Congenital
- Hyperkalemia
74
What can circus conduction occur?
Any part of the heart (AV node; btwn SA node and atria; btwn atria and ventricles)
75
____ accounts for most tachyarrhythmias in cardiac patients
Circus conduction
76
How can circus conduction be stopped?
By converting unidirectional block tissue to bi-directional block (can be done w/ drugs that block Na+ channels in non-pacemaker cells)
77
What is paroxysmal supraventricular tachycardia?
Re-entry in the AV node
78
How is paroxysmal supraventricular tachycardia treated?
Drugs that depress AV conduction, causing bidirectional block (Ca channel blockers, beta blockers, adenosine)
79
What is Wolff-Parkinson-White syndrome?
Re-entry in the AV node through an abnormal electrical pathway (conducts from ventricles to atria)
80
How is Wolff-Parkinson-White syndrome treated?
- Catheter ablation of abnormal electrical pathway
| - Amiodarone first choice to stabilize heart rate
81
When should AV node blockers NOT be used for Wolff-Parkinson-White syndrome? What should be used instead?
- If atrial fibrillation or flutter
| - Use beta blocker, calcium antagonist, adenosine, or digoxin
82
What are the 3 mechanisms of action of antiarrhythmic drugs?
1) Reduce automaticity
2) Block re-entry mechanisms
3) Normalize ventricular rate by slowing conduction through AV node
83
How can you reduce triggered activity?
Block inactivated Na+ or Ca2+ channels in depolarized tissues (prevent conversion to resting state)
84
How can you reduce pacemaker activity?
- Hyperpolarize resting membrane potential
| - Increase membrane threshold potential for activation of Na+ or Ca2+ channels
85
How can you reduce automaticity?
Reduce triggered activity or pacemaker activity
86
How can you block re-entry mechanisms?
1) Reduce phase 0 depolarization, which converts region of unidirectional block to bidirectional block
2) Prolong action potential depolarization, which increases effective refractory period enough that it is greater than conduction time, so re-entry is blocked
87
What happens when you reduce ventricular rate?
Increases time for ventricular filling from atrium, so increase stroke volume and cardiac output, which improves hemodynamics
88
What do class 1 antiarrhythmic drugs do? What are some examples?
- Block Na channels
| - Procainamide, lidocaine, flecainide
89
What do class 2 antiarrhythmic drugs do? What are some examples?
- Block beta-adrenergic receptors
| - Propranolol, metoprolol, esmolol
90
What do class 3 antiarrhythmic drugs do? What are some examples?
- Block K channels
| - Amiodarone, sotalol
91
What do class 4 antiarrhythmic drugs do? What are some examples?
- Block Ca channels
| - Verapamil
92
What do class 5 antiarrhythmic drugs do? What are some examples?
- Work via other mechanisms
| - Magnesium, adenosine, digoxin
93
What is the main function of procainamide (class 1A)?
- Moderately depresses phase 0 and slows conduction
- Prolongs repolarization
- Also blocks K+ channels in phase 3 (prolongs QT interval)
94
What is the main function of lidocaine (class 1B)?
- Minimally depresses phase 0 and slows conduction
| - Shortens repolarization
95
What is the main function of flecainide (class 1C)?
- Greatly depresses phase 0 and slows conduction
| - Little effect on repolarization
96
Which class 1 antiarrhythmic has the strongest Na+ channel blockade?
Flecainide (class 1C)
97
Where are class 1A antiarrhythmics active?
Depolarized cells (active, ischemic)
98
When are class 1A antiarrhythmics used?
- Ventricular tachycardia
- Atrial fibrillation/flutter
* Generally more limited use
99
Why does procainamide have a limited use?
- Depresses hemodynamics
- Blocks K+ channels, so prolongs QT interval and may cause Torsade de Pointes
- May cause lupus like syndrome
100
Where are class 1B antiarrhythmics active?
- Normal tissue, especially atria b/c action potential duration is short
- Block increased in depolarized tissue (ischemic)
101
What does reduced propagation of action potentials and automaticity result in?
Reduced ectopic pacemaker activity, especially in ischemic depolarized tissues
102
When are class 1B antiarrhythmics used? How are they administered?
- Ventricular arrhythmias associated w/ myocardial infarction
- Administered IV
103
What are some adverse effects of lidocaine?
- Tremor, nausea, lightheadedness
- Hearing disturbances
- Slurred speech
- Convulsions
104
What are contraindications for class 1C antiarrhythmics?
Px w/ previous MI, highly arrhythmogenic (b/c of increased re-entry)
105
When are class 1C anti-arrhythmics used?
- Tx of supraventricular (atrial fib and flutter) and life-threatening ventricular arrhythmias
* *Only in px w/ structurally normal hearts
106
Why are beta-blockers used for arrhythmias?
- Reduce phase 4 slope in pacemaker cells by reducing pacemaker current
- Reduce AV conduction velocity by reducing voltage-gated Ca2+ current
- Prolong refractory period in nodal tissues
107
When are beta-blockers used for arrhythmias?
- Control ventricular rate in supraventricular tachycardias
- Terminate and prevent recurrence of paroxysmal supraventricular tachycardia
- Reduce mortality after acute MI
108
What are contraindications to beta blockers?
- Bradycardia and heart block
- Px w/ pulmonary problems
- Decompensated congestive heart failure
- Diabetics
- Wolff-Parkinson-White syndrome
109
Which beta-blocker can be used in cases where beta-blockers are normally contraindicated? Why?
Esmolol b/c has a very short duration of action (half life = 10 min)
110
Amiodarone is a ___ spectrum antiarrhythmic
Wide
111
What are the functions of amiodarone?
- Blocks K+ ion channel in phase 3, prolonging cardiac AP duration *main function
- Blocks inactivated Na+ ion channels
- Blocks Ca2+ ion channels
- Modestly blocks beta receptors
112
What are the functions of sotalol?
- Blocks K+ ion channel in phase 3, prolonging cardiac AP duration
- Also a beta blocker
113
Can class 3 antarrhythmics be used in px w/ structural heart disease?
Yes
114
When is amiodarone used? What is starting to replace it?
- Used for supraventricular and ventricular tachycardia
| - Being replaced by implanted cardioinverter
115
What are the adverse effects of amiodarone?
- Highly lipid soluble, so accumulates in liver, lungs, skin, and other tissues
- Pulmonary toxicity
- Hepatotoxicity
- Hyper and hypothyroidism (b/c contains iodine)
- Sinus bradycardia
- Photosensitivity
116
When is sotalol used?
- Supraventricular tachycardia (equally as effective as amiodarone)
- Ventricular tachycardia (less effective than amiodarone, but preferred when amiodarone toxicity a concern)
117
What are the adverse effects of sotalol?
- May accumulate in px w/ renal disease
- Bradycardia, so contraindicated in px w/ sick sinus syndrome
- Bronchospasm
- Greater risk of Torsade de Pointes than amiodarone
118
What is the function of verapamil?
- Block L-type Ca2+ channels in plasma membrane
| - Slows conduction in AV node
119
When is verapamil used?
- To reduce ventricular rate in supraventricular tachycardias
- Acute paroxysmal supraventricular tachycardia
120
What is a contraindication for verapamil?
Wolff-Parkinson-White syndrome
121
When is magnesium a first line agent?
For Torsade de Pointes, even when magnesium levels are normal
122
What is the mode of action for adenosine?
- Increases K+ conductance (hyperpolarizes)
- Depresses slow inward Ca2+ current
- Slows phase 4 of AV pacemaker AP
123
When is adenosine used?
Given IV for supraventricular tachycardia due to AV node re-entry
124
What are drug interactions w/ adenosine?
Methylxanthines (caffeine, theophylline)
125
What is the mode of action for digoxin?
Decreases AV node conduction (releases ACh and inhibits calcium currents and activates K+ currents)
126
When is digoxin used?
Atrial fibrillation, atrial flutter, and supraventricular tachycardia w/ rapid ventricular response
127
What is a contraindication for digoxin?
Wolff-Parkinson-White syndrome (may cause death)
128
What is the tx for a symptomatic/severe tachycardia?
Immediate cardioversion (electrical or pharmacological)
129
What is the tx for paroxysmal tachycardia?
- IV adenosine/verapamil/beta-blocker
- For WPW, procainamide, flecainide, or amiodarone
- If area of tissue responsible for arrhythmia can be identified, radiofrequency ablation is preferred
130
What is the tx for atrial fibrillation?
- For rate control - verapamil, beta-blocker, digoxin, or amiodarone
- For rhythm control - procainamide, flecainamide, amiodarone, or sotalol
131
What is the tx for ventricular fibrillation?
- Transthoracic defibrillation
| - IV amiodarone, lidocaine, or magnesium may be used as adjunct
132
What is the tx for ventricular tachycardia?
- To terminate episode in unconscious or hypotensive px - cardioversion
- To terminate episode in px w/ stable hemodynamics - IV lidocaine, flecainide, amiodarone, or sotalol
133
What is the tx for Torsade de Pointes?
IV magnesium
134
What is the tx for chronic therapy of ventricular tachycardia?
Cardioverter defibrillator
135
What are the side effects to an implantable cardioverter defibrillator (ICD)?
- Anxiety, depression, PTSD
| - Amiodarone may be used in conjunction to reduce prevalance of accidental ICD shocks
