Antiarrhythmic Drugs Flashcards
(104 cards)
1
Q
What is the most common cause of death in patients with MI or terminal heart failure?
A
cardiac arrhythmias
2
Q
How do you define an arrhythmia?
A
any rhythm that is not normal sinus rhythm
3
Q
What are the two major mechanisms for arrhythmias?
A
1) Abnormal automaticity
2) Abnormal (reentrant) conduction
4
Q
Why is Torsades de pointes unique in the clinically important arrhythmias?
A
it is often INDUCED by antiarrhythmic and other drugs that change the shape of the AP and prolong the QT interval (ex. quinidine and other class III drugs)
5
Q
What is the other cause (not drug induced) of Torsades de pointes?
A
long QT syndrome (heritable abnormal prolongation of QT interval caused by mutations in the Ik or Ina channel proteins
6
Q
What dominates the AP upstroke in most parts of the heart?
A
sodium current
7
Q
What dominates the AP upstroke in the AV nodal cells?
A
calcium current
8
Q
What is “abnormal automaticity”? What is it caused by?
A
spontaneous depolarization of cells without “pacemaker” current (ex. atrial and ventricular myocytes). Can be seen with ischemia, stretch of myocardial fibers, hypoxia, low ions, increased SNS activity
9
Q
What is “abnormal conduction”?
A
conduction of an impulse that does not follow the normal path OR that reenters tissue previously excited
10
Q
What does the PR interval signify?
A
measure of the conduction time from atrium to ventricle through the AV node
11
Q
What does the QRS duration signify?
A
time required for all of the ventricular cells to be activated (intraventricular conduction time)
12
Q
What does the QT interval reflect?
A
duration of ventricular AP
13
Q
What does recovery from inactivation in sodium-dependent cardiac cells depend on?
A
1) membrane potential (varies with repolarization time and extracellular K+ conc)
2) Sodium channel blocking drugs
14
Q
Antiarrhythmic drugs act on what 4 targets?
A
1) Sodium current
2) Calcium current
3) Potassium current
OR
4) Beta adrenoceptors that modulate the currents
15
Q
Describe antiarrhythmic drug classification.
A
Divided into 4 groups or classes with one miscellaneous group
16
Q
What are the class I antiarrhythmic agents? What do they do?
A
Sodium channel blockers- slow conduction in ischemic and depolarized cells and slow/abolish abnormal pacemakers that are dependent on sodium channels by increasing threshold potential and hyperpolarizing
17
Q
What are the class II antiarrhythmic agents?
A
Beta-adrenoceptor blockers
18
Q
What are the class III antiarrhythmic agents?
A
Potassium channel blockers
19
Q
What are the class IV antiarrhythmic agents?
A
Calcium channel blockers
20
Q
What are the class V antiarrhythmic agents?
A
Adenosine, potassium ion, magnesium ion
21
Q
Group 1 antiarrhythmic drugs are divided into what subclasses? What are these based on?
A
Group 1A-1C
Based on dissociation rate
22
Q
What do group 1A drugs do? What is the prototype?
A
Prolong the AP- intermediate dissociation rate
Procainamide
23
Q
What do group 1B drugs do? What is the prototype?
A
shorten AP in some cardiac tissues (ventricle only)- rapid dissociation
Lidocaine
24
Q
What do group 1C drugs do? What is the prototype?
A
have no effect on AP duration- very slow depolarization
Flecainide
25
What are the most selective antiarrhythmic agents?
Group 1B (affect ischemic tissue but has negligible effects on sodium channels)
26
How do sodium channel-blocking drugs target abnormal tissue?
"Use-dependent"- bind to receptors more readily when the voltage channel is open or just inactivated (must bind to the inside of the channel) than when it is fully repolarized and resting (normal cells)
27
List the group 1A antiarrhythmics.
Procainamide, quinidine, disopyramide
28
What are the clinical applications for group 1A antiarrhythmics?
Atrial and ventricular arrhythmias, especially after MI
29
What do group 1A antiarrhythmics do the the PR interval, QRS duration, and the QT interval?
PR: increase owing to channel blocking or decrease owing to antimuscarinic action
QRS: increase
QT: increase
30
What are the adverse effects of group 1A antiarrhythmics?
```
increased arrhythmias (Torsades de Pointes, only at high doses does it show class III activity)
hypotension
lupus-like syndrome (with prolonged PO use, especially if slow acetylator in liver)
```
31
What do group 1B antiarrhythmics target?
ischemic/depolarized Purkinje and ventricular tissue (little effect on atrial tissue)
32
What is the effect of group 1B antiarrhythmics?
1) reduce AP duration (sometimes)
| 2) Slow recovery of sodium channels from inactivation
33
True or false: group 1B drugs have major effects that can be seen on the EKG.
FALSE: they do not harm normal cardiac cells so they have little effect on ECG
34
What are the clinical applications for group 1B antiarrhythmics?
ventricular arrhythmias (tachycardia) and VPBs
35
What are the adverse effects of group 1B antiarrhythmics?
CNS sedation or excitation
36
What do group 1C antiarrhythmics do the the PR interval, QRS duration, and the QT interval?
- NO effect on QT interval or AP duration
- Slow conduction velocity in atrial and ventricular cells
QRS: increase
PR: slight increase
37
What group 1A antiarrhythmic can you not use with digoxin?
quinidine (reduces it clearance and increases serum concentration)
38
What usually exacerbates the toxicity of group 1 drugs?
hyperkalemia
39
How do you reverse an overdose on group 1 antiarrhythmics?
sodium lactate
| pressor sympathomimetics
40
Lidocaine has what ROA? Why?
IV or IM but NEVER orally, because of high first-pass effect and cardiotoxic metabolites. However, really lipophilic, so it will distribute into fat tissue when given IV and needs 2-phase loading protocol.
41
What is the group 1b antiarrhythmic that can be taken orally? What is the down side?
mexiletine- GI distress common and limits usefulness
42
What are the clinical indications of flecainide?
approved only for refractory ventricular tachycardias and certain intractable supraventricular arrhythmias (that fail to respond to other drugs)
43
Flecainide is more likely than any other antiarrhythmic drug to have what effect?
proarrhythmic (exacerbate or precipitates arrhythmias). this was shown in CAST to actually increase chance of death after MI
44
What is the mechanism of group 2 antiarrhythmics?
cardiac beta receptor blockage and reduction in cAMP which reduces both sodium and calcium currents and suppresses abnormal pacemakers
45
What are the beta-blockers used in arrhythmia treatment? What types?
Propranolol (atrial/ventricular arrhythmia)
Metoprolol (off label for arrhythmias)
Acebutolol (ventricular arrhythmia)
Esmolol (supraventricular arrhythmia)
46
What part of the heart is very sensitive to beta blockers? What do group 2 antiarrhythmics do the the PR interval, QRS duration, and the QT interval?
AV node
prolong the PR interval (decrease phase 4 slope)
no effect on QRS or QT
47
What is the clinical use for esmolol in arrhythmia treatment?
IV administration in acute supraventricular arrhythmias
48
What is the clinical use oral beta blockers in arrhythmia treatment?
prophylactic drugs in patients who have had an MI
49
What are the adverse effects of beta blockers?
- bronchospasm
- cardiac depression
- AV block
- Hypotension
50
List the group 3 antiarrhythmics.
```
Dofetilide
Ibutilide
Sotalol (chiral compound)
Amiodarone
Dronedarone
```
51
What is the hallmark of group 3 antiarrhythmics?
prolongation of AP duration (and ERP) due to blockage of IKr (responsible for repolarization)
52
What does amiodarone do the the PR interval, QRS duration, and the QT interval? Why?
PR: increase slightly (beta)
QRS: increase
QT: LARGE increase (Ik)
Blocks sodium, calcium, potassium channels and beta receptors.
53
What do ibutilide and dofetilide do the the PR interval, QRS duration, and the QT interval?
large QT increase
54
What does sotalol do the the PR interval, QRS duration, and the QT interval?
Increase PR interval (beta block)
| Increase QT interval (Ik block)
55
What drug is considered to be the most efficacious of all antiarrhythmic drugs?
amiodarone: used with atrial and ventricular arrhythmias, and as drug of choice in cardiac rescuscitation
56
What are the toxicities of amiodarone?
```
Thyroid abnormalities (structural analog of thyroid hormone)
Deposits in skin and cornea
Pulmonary fibrosis
Optic neuritis (blindness)
RARE torsades
```
57
What is the clinical application for sotalol?
atrial, ventricular AV nodal reentrant arrhythmias (including v tach). Less effective but less toxic than amiodarone
58
What are the AAs of sotalol? Contraindications?
dose related torsades
Cardiac depression
Contraindications: QT>450msec, Renal insufficiency, asthma, CHF, AV block, bradycardia, MI
59
What is the clinical application for ibutilide? Adverse effects?
treatment of acute atrial fibrillation and atrial flutter
| AE: torsade de pointe, not for patients iwth long QT
60
What is the clinical application for dofetilide? Adverse Effects?
treatment and prophylaxis of atrial fibrillation (interrupts re-entry in atrium)
AE: torsades de pointes, transient asystole
61
True or false: all L-type calcium channel blockers are useful in antiarrhythmic therapy.
FALSE: dihydropyridines are NOT useful, because they actually stimulate reflex sympathetic heart stimulation which could worsen arrhythmias
62
What are the effects of group 4 antiarrythmics?
- State and use-dependent selective depression of calcium current
- AV conduction velocity is decreased
- Effective refractory period and PR interval is increased
63
What is the major clinical use of group 4 antiarrhythmics?
Verapamil and Diltiazem prevent and converting AV nodal reentry (nodal tachycardia) to normal sinus rhythm
64
What are the major adverse effects of group 4 antiarrhythmics?
depression of contractility
reduce AV node automaticity
depress AV conduction
decrease BP
65
Group 4 antiarrhythmics should be avoided with what condition?
ventricular tachycardias, CHF, sinus bradycardia, or AV block
66
How does adenosine work in treatment of arrhythmias?
given in high doses as IV bolus and blocks conduction of AV node by hyperpolarizing tissue through increased Ik1 and reducing calcium current
67
What is the drug of choice for AV nodal arrhythmias (PSVT)?
adenosine
68
What is the half-life of adenosine?
around 10 s (must give IV)
69
What are the adverse effects of adenosine?
flushing, hypotension, transient asystole (<3s) transient chest pain and dyspnea
70
What is the use of potassium in treating arrhythmias?
Hypokalemia- increased incidence of arrhythmias (especially in patients on digitalis)
Hyperkalemia- depress conduction and can cause reentry arrythmias
*Need to balance and normalize
71
What is the use of magnesium ion in treating arrhythmias?
poorly understood, possibly increase sodium potassium ATPase activity
72
What are the adverse effects of Mg ion?
muscle weakness
| if too high, respiratory paralysis
73
List the non-pharmacologic treatment options for arrhythmias.
1) external defibrillation
2) implanted defibrillators
3) implanted pacemakers
4) radiofrequency ablation of arrhythmogenic foci via catheter
74
What is propafenone? What is it used for?
```
class 1C agent with beta-adrenergic properties.
A fib, A flutter in patients WITHOUT heart disease
```
75
What are the drugs of choice for interrupting re-entry?
Class 1A and 1B
Class III
NOT class 1C, ventricular problem so contraindicated!!
76
When do you use dronedarone?
paroxysmal atrial fibrilliation and maintenance of sinus rhythm after cardioversion in people without CHF!
77
What is "triggered automaticity"?
"echo" depolarization in response to preceding depolarization. Can be early afterdepolarization (EAD) or delayed afterpolarization (DAD)
78
What is an APB?
premature atrial beat
79
What might cause APBs in a healthy 21 year old?
enhanced automaticity of an atrial conducting fiber (probably due to increased intake of caffeine)
80
Pacemaker channels are linked to what other systems?
1) muscarinic receptors (parasympathetic nervous system)
2) sympathetic nervous system
3) adenosine receptors
81
How would you treat reduced automaticity of the SA node (sinus arrest)?
Atropine (if too much vagal tone)
| Epinephrine (beta agonist)
82
What is a VPB?
premature ventricular beat
83
Does a VPB count as normal or abnormal automaticity?
abnormal (ventricular myocytes do not normally have "pacemaker" activity)
84
How do sodium channel blockers stop re-entry?
- Decreased rate of depolarization (phase 0)
- Increased effective refractory period, because there is a slower voltage-dependent recovery of the Na+ channels with the drug bound
85
Ventricular tachycardia is most commonly due to what?
organized re-entry of impulses around an anatomic barrier (ex. area of myocardial infarction or ischemia)
86
What conditions are required for re-entry to occur?
1) Anatomic or physicologic obstacle
2) Unidirectional block
3) Conduction time exceeds effective refractory period in "slow" circuit
87
What typically triggers re-entry?
premature impulse (automaticity)
88
How do K+ channel blockers stop re-entry?
prolongation of the ERP in the slow conducting limb prevents re-entry back into the "slow side"
89
Describe the pharmacokinetics of amiodarone.
- Highly lipophillic
- Eliminated VERY slowly (t1/2 = 20-100 days)
- Oral or IV loading dose needed for rapid onset
- CYP3A4 metabolized and inhibitor
90
What are the top 3 drugs for treating ventricular tachycardia?
1) Amiodarone
2) Lidocaine
3) Procaineamide
91
Having an EF below what percentage places a person at high risk of sudden cardiac death due to ventricular tachycardia/fibrillation?
<35%
92
How would you treat someone at high risk of sudden cardiac death due to ventricular tachycardia/fibrillation?
Implantable cardiac defibrillator
93
What are the two strategies for treating arrhythmias due to re-entry into the atrium (a fib)?
1) Rhythm control strategy
| 2) Rate control strategy
94
What is the rhythm control strategy?
Interrupting re-entry within the atria using Class I and III antiarrhythmic drugs as with ventricular tachycardia
95
What is the rate control strategy?
Controlling rate of ventricular activation from atrial re-entry by slowing conduction of the atrial impulses through the AV node
96
What did the AFFIRM trial discover in the comparison of rhythm versus rate control of atrial fibrillation?
Rate control (digoxin, beta blocker, diltiazem and verapamil + warfarin) is better than rhythm control.
97
What 3 drugs slow conduction through the AV node to prevent supraventricular arrhythmias?
1) Calcium channel blockers (verapamil/diltiazem)
2) Beta blockers (propranolol/metoprolol)
3) Digoxin (vagal effect)
98
What is the MOA of digoxin?
Inhibits Na+/K+ ATP pump, reduces SA node automaticity (increases intracellular calcium)
99
What are the conflicting effects of digoxin?
Vagal= antiarrhythmic effects (reduce SA automaticity and AV conduction, interrupts reentry in AV node)
Arrhythmogenic effets= increased normal automaticity, may lead to DADs from calcium overload
100
Arrhythmias originating in the AV node are called what? What does this look like on an ECG?
paroxysmal supraventricular tachycardia (simultaneous activation of ventricle and atria (retrograde)).
Narrow QRS, regular rhythm, no p waves
101
What problems can Wolff Parkinson White Syndrome cause?
Direct connection from atria to ventricle leads to:
Ventricular fibrillation (from multiple atrial signalling)
Supraventricular tachycardias
102
What effect does vagal stimulation have on atrial tissue?
"Paradoxical effect" where it shortens AP duration, increases conduction velocity, and decreases ERP
103
What is contraindicated in Wolf-Parkinson white syndrome?
```
Digoxin (increases vagal afferents to heart which will result in increased conduction velocity and a potential for induction of ventricular fibrillation)
Do not use class IV or Ib either! (could cause v fib as well)
```
104
What is the best way to treat someone with WPW syndrome arrhythmias (a fib and a flutter)?
1) combination therapy (Class Ia and II)
| 2) single agent (Class III or class Ic)
