antiarrhythmics (exam 2) Flashcards
(138 cards)
1
Q
arrhythmia
A
disturbance of electrical signals in the heart to an irregular rate or rhythm
2
Q
how do arrhythmias occur
A
damage or structural abnormality in tissue
electrolyte abnormality
drugs that can alter cardiac functions
3
Q
symptoms of arrhythmias
A
palpitations
lightheadedness
syncope
fatigue
cardiac arrest
4
Q
how are arrhythmias classified?
A
where they originate
how the affect heart rate
type of impulse abnormality
5
Q
location of arrhythmias
A
atrial (supraventricular)
ventricular
6
Q
effect on HR of arrhytmias
A
tachycardia
bradycardia
7
Q
type of abnormality of arrhythmias
A
disturbance of impulse formation (ectopic, EAD, DAD)
disturbance of impulse conduction (heart block, reentry)
8
Q
HCN channels have a key role in ___________________ and are important ________________
A
controlling cardiac pacemaker activity
regulators of neuronal excitability
9
Q
HCN channels
A
voltage gated ion channel
dually gated by membrane hyper polarization and cyclic nucleotides
10
Q
funny current (If)
A
HCN channel in SA node generates this
responsible for spontaneous depolarization that initiates each heart beat
11
Q
what sets the heart rate?
A
funny current
12
Q
____________ HCN channel expression in enlarged ventricles can contribute to arrhythmias
A
increased
13
Q
abnormal HCN channel function can lead to
A
irregular heart rhythms like sinus bradycardia or a-fib
14
Q
which HCN channel is most important in arrhythmias?
why?
A
HCN4
regulates heart rate and rhythm
15
Q
HCN4 channel
A
nonselective cation channel
conducts Na and K ions through plasma membrane
16
Q
HCN4 channels generate a ___________________ causing cellular ________________
A
net inward current (If)
depolarization
17
Q
upon activation by cAMP, there is a ____________ shift of the HCN4 activation curve and If ______________ causing ____________________
A
positive
increases
cellular depolarization
18
Q
Ivabradine (IVA)
A
blocks HCN from the intracellular side only
causes cellular hyperpolarization
19
Q
automaticity is due to
A
leaky Na channels (HCN channels)
20
Q
HCN channels allow for _____________. The threshold potential is
A
influx of Na (funny current)
-40mV
21
Q
“slow response” actions potentials
A
nodal APs found in the SA and AV node
22
Q
pacemaker depolarization phase occurs due to
pacemaker repolarization phase occurs due to
A
Ca2+ influx
K+ efflux
23
Q
myocardial action potential phase 4
A
at rest (-90mV)
24
Q
myocardial action potential phase 0
A
depolarization due to Na influx
25
myocardial action potential phase 1
notch due to K efflux
26
myocardial action potential phase 2
plateau due to Ca influx and K efflux
27
myocardial action potential phase 3
depolarization due to K efflux
28
absolute refractory period of myocardial action potential
phase 0 to part of phase 3
29
can you generate an action potential during the absolute refractory period?
no, impossible!
30
relative refractory period
remainder of phase 3
31
can you generate an action potential during the relative refractory period?
yes, but it is difficult
32
refractory period is due to the
inactivation of VG Na channels
33
cardiac conduction pathway
SA node --> AV node --> bundle of His --> purkinje fibers
34
longer duration in cardiac muscle is crucial for
preventing summation of contractions and maintaining a coordinated heartbeat
35
electrocardiogram
test that measures the electrical signals that control heart rhythm
measures electrical impulses
36
P wave
atrial depolarization
37
QRS complex
record of movement of electrical impulses through the ventricles (ventricular depolarization)
38
ST segment
when the ventricle is contracting but no electricity is flowing through it
39
T wave
lower heat chambers are resetting electrically and preparing for the next contraction
(ventricular repolarization)
40
The ST segment appears as a
straight level line between the QRS complex and T wave
41
QT prolongation
when the corrected QT interval is greater than 440 mx in men and 460 ms in women
42
QT prolongation can lead to life threatening ventricular tachyarryhtmia called
torsade de pointes (TdP)
43
PR interval time
0.12-2 sec
44
QT interval time
around 0.38 s
45
where does atrial repolarization occur?
QRS complex
46
ectopic pacemaker
cardiac cells gain abnormal automaticity and begin spontaneously depolarizing
47
delayed afterdepolarization
2nd depolarization occurs immediately following a complete action potential
48
early afterdepolarization
2nd depolarization occurs during action potential phase 2 or 3
49
heart block
failure in the normal propagation of AP from atrium to ventricle
50
heart block results in
bradycardia or skipped beats
51
reentry (accessory pathway)
impulse reenters and excites areas of the heart more than once due to dysfunction of the refractory period
52
normal action potentials cancel each other out in the
third phase
53
heart rate and rhythm is set by
whichever tissue is spontaneously generating action potentials most frequently
54
which node controls heart rate and rhythm
SA node (60-100 APs/min)
55
exception to tachyarrhythmias
heart block - bradyarrhythmia
56
arrhythmias that require treatment fall into one of these categories
significantly decrease cardiac output
precipitate more serious arrhythmias
precipitate thromboembolism
57
non pharmacological approached for arrhythmias
ablation therapy
electrical cardioversion
vagal maneuvers
58
antiarrhythmic medications can be classified as
rhythm control or rate control drugs
59
rhythm control drugs
decrease the automaticity of ectopic pacemakers or reentrant loops more than that of the SA node
60
rhythm control drugs work at the _______________ level while rate control drugs work at the _________________ level
myocardial action potential
nodal action potential
61
rhythm control drugs are used for
chemical cardioversion or in prevention of arrhythmia
62
rate control drugs
alter the heart rate but do not usually affect the rhythm
can reduce HR in tachyarrhythmia but the rhythm remains abnormal
63
Class Ia Na channel blockers
disopyramide (Norpace)
quinidine (Quinidex)
procainamide (Procan)
64
Class Ib Na channel blockers
Lidocaine (xylocaine)
mexiletine (mexitil)
65
class Ic Na channel blockers
flecainide
Propafenone (rhythmol)
66
class III: K channel blockers
amiodarone
dronedarone (Multaq)
Dofetilide
Ibutilide (corvert)
Sotalol (Betaspace)
67
drugs that are rhythm control medications
Na channel blockers (class I)
K channel blockers (class III)
68
drugs that are rate control medications
Class II: beta blockers
Class IV: non-DHP CCBs
MSC
69
MSC rate control medications
digoxin
adenosine (adenocard)
70
primary way to control rhythm for rhythm control medications
prolonging the inactivation of VG Na channels which delays the next action potential
71
inactivation of the VG Na channels is ______________ dependent
time and voltage
72
Class I antiarrhythmics MOA
directly binds to VG Na channels and keeps them inactivated
increases the effective refractory period
73
Class III antiarrhythmics MOA
prolonging the action potential by blocking VG K channels
increases the action potential duration
74
Na channel blockers used as rhythm control drugs bind more easily to ____________ channels but bind poorly to _______________ channels. These are called _________________.
open and inactivated
closed
use-dependent or state-dependent
75
effect of blocking open channels
slowing of phase 0 of AP
76
effect of blocking inactive channels
keeps them inactive and prolongs refractory period
77
which Na channel blockers prolong QRS on ECG?
which don't?
Class Ia and Ic
Class Ib
78
Class Ia Na channel blockers MOA
intermediate on-off (moderate block)
prolongs the AP duration
79
Class Ib Na channel blockers MOA
fast on-off (weak block)
slightly shortens the AP duration
80
Class Ic Na channel blockers MOA
slow on-off (strong block)
does not alter the AP duration
81
considerations of use for Class Ia drugs
effective against atrial and ventricular arrhythmias
can cause QT prolongation due to K channel block which causes Torsades
82
Procainamide ADRs
lupus like syndrome (50% patients)
hypotension
Nausea/diarrhea, rash, fever, hepatitis
83
Procainamide's metabolite ______________ has stronger ____________________ block and can increase the risk of _______________. It also accumulates in ___________-
NAPA
K channel block
torsades
renal failure
84
Quinidine ADRs
mild antimuscarinic effects
N/V/D
cinchonism (HA, dizziness, tinnitus at toxic concentrations)
85
quinidine is an inhibitor of
CYP2D6
86
quinidine is also used to treat
malaria
87
disopyramide ADRs
moderate antimuscarinic effects
negative inotropic effect --> HF
88
Class Ib Na channel blockers are effective against
ventricular arrhythmias, especially after MI
89
lidocaine ADRs
neurologic - paresthesia, tremor, nausea of central origin, lightheadedness, seizures
90
lidocaine is only used for arrhythmias bu
IV route due to extensive 1st pass metabolism by oral route
91
mexiletine ADRs
N/V (can be minimized with food)
neurological - tremor, blurred vision, lethargy
92
mexiletine is an analogue of ______________ that was modified to reduce ________________
lidocaine
first pass metabolism so it can be taken orally
93
class Ic Na channel blockers are used for
atrial arrhythmias and a-fib (pill in pocket)
94
Class Ic Na channel blockers should not be used in patients with a history of
structural abnormalities (MI, HF) because they are more likely to cause an arrhythmia
95
most common ADR of flecainide
blurred vision
96
Propafenone is given as a _________ and reduces __________________ so avoid in _______________
racemate
heart rate (beta 1) and increases risk of bronchospasm (beta 2)
asthma/COPD
97
Class III: K channel blockers target the
rapid delayed rectifier K channels (IKr)
98
how do K channel blockers restore normal rhythm?
specifically block K channels responsible for phase 3 which prolongs AP
increases refractory period
99
cardiac tissue which is ____________ remains in the _____________ and is unable to reactivate
overactive
refractory period
100
considerations for use of K channel blockers
QT prolongation (risk of torsades)
101
K channel blockers become less effective in which conditions?
ischemic myocardial tissue
hyperkalemia
102
amiodarone contains _______________ which in a dose of 200mg releases _____ of iodine which is _____________ higher than the normal iodine daily intake
two iodine molecules
6 mg
20x
103
amiodarone can be considered a
nonselective anti arrhythmic
104
amiodarones brand spectrum of action may account for its
high efficacy and relatively low incidence of TdP despite causing QT prolongation
105
amiodarone is a highly _______ drug and is highly ______________
lipophillic
bound to plasma proteins
106
Due to accumulation in tissue and a long half life, amiodarone can be detected for ____________ following discontinuation
up to 1 year
107
amiodarone inhibits
3A4, 2C9, a p-gp
108
amiodarones active metabolite is
desethylamiodarone
109
what is the most common ADR for amiodarone?
pulmonary fibrosis
110
ADRs of amiodarone
pulmonary fibrosis
hepatitis
photodermatitis
UV photosensitivity
asymptomatic corneal micro deposits
QT prolongation
nausea
peripheral neuropathy
111
what issue with the thyroid is more common?
hypothyroidism due to very high iodine levels
112
what is the most commonly used rhythm control drug?
amiodarone
113
6 Ps of amiodarone
Prolongs AP duration
photosensitivity
pigmentation of skin
peripheral neuropathy
pulmonary alveolitis and fibrosis
peripheral conversion of T4 to T3 (hypothyroidism)
114
dronedarone is designed to mimic
amiodarone but with less toxicity and shorter half lofe
115
how is dronedarone different from amiodarone?
removal of iodine atoms
multiple MOAs
116
is dronedarone more effective than amiodarone?
no
has other toxic effects (death, stroke, hospitalization for HF)
117
what is sotalol's additional mechanism of action?
nonselective beta blocker
inhibits K channels
118
does sotalol bind to plasma proteins?
no
119
considerations for use of sotalol
few drug interactions
high risk for torsades
120
dofetilide and ibutilide are __________ as K channel blockers
very selective
121
Ibutilide is only available as _____ and is used for ____________________
IV
chemical cardioversion in atrial flutter/fibrillation
122
beta blockers and CCBs are often used as first line in
atrial fibrillation
123
Digoxin MOA
increases intracellular Ca by inhibition of Na/K/ATPase, leading to positive inotropic effect
increases cardiac contractility
124
adenosine is a naturally
occurring purine nucleoside that forms from the breakdown of ATP
125
adenosine binds to
adenosine receptors (A1, A2, A3)
126
activation of the A1 receptors in cardiac tissue predominately affects the _______ by _______________________
AV node
inhibition of Ca channels and activation of K channels
127
activation of the A2 receptors in ____________ causes ____________
arterial smooth muscle
vasodilation which lowers blood pressure
128
adenosine receptors cause numerous effects such as
bronchospasm
sedation
129
ADRs of adenosine
flushing, headache, hypotension
dyspnea, burning sensation in the chest
nausea
130
adenosine is less effective in the presence of
adenosine receptor antagonists (caffeine, theophylline)
131
what makes adenosine ideal for continuous IV use?
short half life of 10s
132
torsades de pointes
polymorphic ventricular tachycardia characterized by "twisting of the QRS" which is proceeded by prolongation of the QTc interval
133
does everyone die from TdP?
no, it is potentially fatal but sometimes it resolves on its own
134
what type of arrhythmia is torsades?
early afterdepolarization
135
what is the most common cause of TdP?
drug induced in patients with underlying risk factors
136
drug induced QT prolongation is defined as
QTc of 500ms or greater
or
increase of 60ms or greater in QT interval
137
what are characteristics of drugs that are associated with TdP?
drugs that block IKr and prolong the action potential
138
what are the most common drugs that are associated with TdP?
class Ia and III antiarrhythmics
