Drugs used in Cardiac Arrhythmias Flashcards
1
Q
What causes arrhythmias
A
Abnormal pacemaker activity or abnormal impulse propagation
2
Q
What is the goal of therapy of arrhythmias
the actual arrhythmia
A
to reduce ectopic pacemaker activity and modify conduction/refractoriness to disable circus movements
This modifying happens in the reentry circuits
3
Q
What are the major pharmacologic mechanisms available to accomplish what arrhythmias do?
4 total
A
- sodium channel block
- bloackade of sympathetic autonomic effects in the heart
- prolongation of the effective refactory period
- calcium channel block
4
Q
What are antiarrhythmic drugs classified by?
A
Their effect on the myocardium
5
Q
Are antiarrhythmic drugs used in pts with non-life threatening arrhythmias?
A
No, this can increase mortality
especially in pts with structural heart disease
6
Q
what do antiarrhythmic drugs do at the SA node
specifically the pacemaker cells
A
decreases automaticity of ectopic pacemakers
7
Q
what do antiarrhythmic drugs do to the refractory period
A
- reduce conduction and excitability
- increase the refractory period
8
Q
How do antiarrhythmic drugs work?
A
selectively blocking sodium or calcium channels of depolarized cells
9
Q
What is automaticity?
A
ability to produce its own
10
Q
What phase do channel-blocking drugs readily bind to activated channels?
A
Phase 0
11
Q
MOA of channel blocking drops
What phase do channel-blocking drugs readily bind to in-activated channels?
A
phase 2
12
Q
MOA channel blocking drugs
How do channel blocking drugs bind to rested channels?
A
Poorly or not at all
13
Q
What type of MOA are channel-blocking drugs described as?
A
use-dependent or state-dependent
14
Q
what happens when there is a more active a channel
For MOA of channel blocking drugs
A
more blocking
15
Q
MOA of channel-blocking drugs
What phase do channel blocking drugs reduce?
A
Phase 4
16
Q
MOA of channel blocking drugs
What channels do channel blocking drugs block?
A
Sodium or calcium channels
17
Q
MOA of channel blocking drugs
The more the heart acts up the ___ the drug will work?
A
better
because as activity increases = blocking can increase
18
Q
What do channel blocking drugs do to the ratio of sodium/calcium permeability to potassium permeability
A
reduces the ratio between Na+/Ca2+ perm to K+ perm
19
Q
MOA of channel blocking drugs
what do beta-adrenoceptor blocking drugs do to phase 4? What is the process?
A
indirectly reduces phase 4
-by blocking the positive chronotropic action of norepipherine in the heart
20
Q
Phase 4 of the AP of the heart
A
Resting potential
K+ moves out of the cell to repolarize
21
Q
Phase 0 of the AP of the heart
A
Na influx to depolarize to threshold
then RAPIDLY depolarizes beyond 0mV
22
Q
Phase 1 of the AP of the heart
A
Partial repolarization
-brief influx of chloride and efflux of K+
-membrane potential decreases slightly
23
Q
Phase 2 of the AP of the heart
A
Plateau phase
opens L-type Ca2+ channels and there is an influx of Ca2+
~0mV
24
Q
Phase 3 of the AP of the heart
A
Rapid repolarization
K+ moves out of the cell
-back to -90mV
25
When do we use sodium channel blockers
the sodium channels let in too much sodium (more than the cycle allows) ???????????
26
What is happening in the heart during the P-wave? What phase does this correlate to
SA node signals and there is Atrial contraction
-phase 0
27
What is happening in the heart during the QRS complex? What phase does this correlate to?
Depolarization of the ventricles
-phase 0
Repolarization of the ventricles
-start of phase 1
28
What is happening in the heart during the T-wave? What phase does this correlate to?
Ventricular repolarization
phase 3
29
What type of channels does Calcium come through in phase 2
voltage gate L-Type
30
action potential phase 0
upstroke
31
what is a Reentry Arrhythmias
continuous repetitve propagation of an excitatory wave returning to its site of origin
32
What arrhythmias can reentry cause?
| 6 total
sinus note reentry
atrial flutter
atrial fibrillation
av noda reentry
av reentry using a bypass (AVRT)
ventricular tachyarrhythmias
33
what types of conduction do reentry arrhythmias rely on
critically depressed conduction
34
# reentry arrhythmia
What does steady-state reduction do?
reduces the excitatory currents to a level below that required for propagation
35
# reentry arrhythmia
What does prolongation do?
prolongs the recovery time of the channels that still reach rested/available state
-increases the effectiveness of the refractory period
36
what 2 mechanisms of antiarrhythmic agents slow conduction
1. Steady-state reduction in available unblocked channels
2. Prolongation (refactory period)
37
What do antiarrhytmic drugs suppress?
ectopic automaticity and abnormal conduction
38
What can happen as antiarrhythmia drug dosage is increased? what does this result in?
can depress conduction in normal tissue
result: drug-induced arrhythmias
39
What can antiarrhytmia drugs become and when?
Proarrhythmic
during fast heart rates
40
What does antiarrhythmic drugs turned proarrhythmic lead to?
Acidosis
Hyperkalemia
ischemia within myocardial tissue
41
What does acidosis do in terms of pharmacological function
slows recovery from the block for most drugs
42
What is Singh-Vaughan Williams classifications
method for classifying drug action
4 classes
43
Singh-Vaughan Williams class 1
Action is a sodium channel blockade
44
singh-vaughn williams classification class 1a MOA
prolongs the APD and has intermediate dissociation kinetics
44
Lidocaine is _____ use in what?
Second Use
serious ventricular arrhythmias
45
What level of toxicity and effectiveness does Lidocaine have in arrhythmias
Low incidence of toxicity
high degree of effectiveness
46
How is Lidocaine administered for arrhythmias
IV
47
What is the MOA of Lidocaine
blocks activated and inactivated sodium channelss with rapid kinetics
48
# for Lidocaine
what does the inactivated state block ensure?
a greater effect on cells with long action potentials (purkinje fibers or ventricular cells)
49
What does Lidocaine do to depolarized cells?
increases activation and slows unbinding kineticss
results: selective depression of conduction
50
Why does Lidocaine have to be admisitered patenterally (IV)?
extensive first pass hepatic metabolism if given orally
51
what is the half life of lidocaine
1-2 hours
52
What is the loading dose of lidocaine in adults? How long is it administered over?
150-200mg over 15 minutes
53
What is the maintenance infusion of lidocaine following the loading dose?
2-4mg/min
54
What is the therapeutic plasma level goal of lidocaine once on a maintenance dose?
2-6 mcg/mL
55
What is the loading dose of Lidocaine for adults with ventricular arrhythmias (associated with MI)
IV 1.0-1.5 mg/kg
56
if required, what is the second bolus dose of Lidocaine for ventricular arrhythmias? when can it be administerd
0.75-1.5mg/kg
1.5
5-10 minutes after first dose
57
If the loading doses and first dose don't work, what bolus dose of lidocain can be administered for ventricular arrhythmias?
what is the timing and max dose?
0.5-0.75 mg/kg
every 5-10 minutes
max dose: 3mg/kg
58
What is the plasma clearance in pts with liver disease? what is the volume of distribution?
markedly reduces and volume of distribution is increased
59
How do you adjust lidocaine dose given to patients with liver disease?
maintenance dose is decreased
loading dose is normal
60
what drugs decrease lidocaine clearance? what impact does this have?
Drugs that decrease liver blood flow (propranolol, cimedtidine)
increases toxicity risk
61
Lidocaine is one the ____ cardiotoxic of the current sodium channel blockers
least
62
What are symptoms of cardiotoxicity?
proarrhythmic effects
SA node arrest
impaired conduction
ventricular arrhythmia
63
What can Lidocaine cause in patients with preexisting heart failure
hypotension
64
What type of adverse effects are most common for lidocaine
neurological in nature
65
What neurological symptoms occur with lidocaine
paresthesia, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions
66
For lidocaine, what population experiences the adverse neurological effects the most?
elderly or vulnerable patiens
67
Two types of more effective B-blocking drugs class two?
propranolol and nadolol
68
what type of drug is esmolol
short acting b-blocker as an antiarrhytshmic drug for intraoperative and acute arrhythmias
69
MOA of flecainide and the effects (
slows conductsion in the cardiac tissue by altering ions
-causes: slight prolongation of refractory periods, decreases rate of rise of AP, increases electrical stimulation threshold, local anesthetic and moderate negative inotropic effects
70
What type of drug class is flecainide
class 1c
71
what is the dosage of Flecainide
50mg, 100mg, 150mg PO
72
What are indications for Flecainide?
1. paroxysmal A-fib/flutter and paroxysmal SVT
2. Prevention of ^^ in patients without structural heart disease
3. prevention of documented life threatening ventricular arrhythmias in pts without structural heart disease
73
for what type of patients is flecainide not reccommended for?
less severe ventricular arrhythmias
Why: proarrhytmic effects (the risk doesn't outweigh the benefit)
74
CI of use of Flecainide (4)
1. hypersensitivity to the drug
2. pre-existing 2nd or 3rd degree AV block with RBB when associated with L hemiblock
3. cardiogenic shocck
4. concurrent use of ritonavir
75
Most common adverse reactions of flecainide?
| list 5 general topics
1. dizziness (mc)
2. visual dis
3. dyspnea
4. Cardiovascular (palpation, chest pain, edema, tachycardia, proarrhythmic, sinus node dysfunction)
5. CNS (headache, fatigue, nervousness, fever, mailaise, hypoesthesia, paresis, ataxia, vertigo etc)
76
what do class three drugs do?
prolong the effective refractory period by prolonging the AP
77
what is the MOA of Class three drugs
* blocks potassium channels in cardio muscle or enhances inward sodium channels
* this prolongs the AP
* can POSSIBLY cause prolonged Q-T intervals
78
what is the risk of QT interval prlongation
ventricular arrhythmias
b/c long QT is an irregularity of the electival activity
79
Are QT interval prolongation complications common or rare?
rare
80
How is amiodarone administered
IV or Oral
81
What is amiodarone mainly used for?
treating serious ventricular arrhythmias
82
What can Amiodarone also be used to treat?
Supraventricular arrythmias (like A-fib)
83
What class type is amiodarone? what does this mean the MOA is?
Class 3
prolongs the AP duration by blocking IKr
84
what can be blocked secondarly by amiodarone
IKs (chronic use)
Inactivated sodium channels
85
What does amiodarone not do?
adrenergic action and calcium channel blocking action
86
what is the bioavailability of amiodarone
35-65%
87
what is the half life of amiodarone
rapid- 3-10 days 50% of drug
this slows down to become several week half lifes
88
After discontinuation, how long does amiodarone stay in the body
1-3 months
89
what is the total loading dose of amiodarone? What steps are taken?
10g
0.8-1.2g daily dose
90
what is the maintenance dose of amiodarone
200-400mg daily
91
What is amiodarone a substrate for?
liver cytochrome CYP3A4
92
What impact does inhibatory liver enzyme drugs have on amiodarone
increased levels since liver enzyme is decreased
93
In drugs that increase CYP3A4, what happens to amiodarone
decreased concentration when coadministered
94
What can amiodarone do to other drugs in the system
Increase levels because it blocks liver enzymes which results in drugs staying in the system longer
(statins, digoxin, warfarin)
95
Following the initiation of amiodarone, what should happen to warfarin dose?
reduce the warfarin does by 1/3 -1/2
monitor prothrombin times closely
96
In patients with A-fib, what is the dose and result of amiodarone?
low dose of 100-200mg/d
maintains normal sinus rhythms
97
what is amiodarone most effective for?
PRevention of recurrent ventricular tachycardia
98
what is the first dose of amiodarone for ventricular fib or pulseless VT
300s mg IV/IO push
99
what is the second dose of amiodarone for ventricular fibrillation or pulseless VT
150 mg IV/IO push
100
For pts with A-fib, heart failure or rapid ventricular response what is amiodarone useful for?
controlling the ventricular response
101
What is the adverse side effects of amiodarone on the heart?
bradycardia and heart block (in pts with prexisting SA or AV disese)
102
where does amiodarone accumulate in the body?
| 5 things
Heart (MOST COMMON)
lung
liver
skin
tears
103
wha is the most important adverse effect of amiodarone
Pulmonary toxicity even in low doses (<200mg)
(may lead to pulmonary fibrosis)
104
What is the adverse effect of amiodarone on the liver?
hypersensitivity hepatitis
abnormal liver function tests
105
What is ammiodarone's impact on thyroid hormones?
Blocks T4 and T3 from eachother
106
What class are calcium channel blocking drugs?
class 4
107
what drug is the prototype of Class 4 drugs?
verapamil
108
What channels does verapamil block?
activated and inactivated L-type calcium channels
109
What does verapamil cause in the PV systme?
peripheral vasodilation
-beneficial for hypotension and vasospastic disorder
110
what is the MOA of class 4 verapamil
-AV nodal conduction and refractory period are prolonged
-slowed SA node (hypotensive action can result in small increase of SA rate)
111
what is the main indication for use of verapamil?
Supraventricular tachycardia
112
What is verapamil and adenosine preferred over?
older treatments
-propranolol, digoxin, edrophonium, vasoconstriction and cardioversion)
113
what is the agent of first choice for patients in SVT without heart failure or AV/SA nodal disease
adenosine
114
what is the agent of second choice for patients in SVT without heart failure or AV/SA nodal disease
parenteral verapamil
115
what is the Verapamil dosage (initial and time) and second dose?
5mg over 2-5minutes
2nd: 5mg bolus if needed
116
4 drugs that are miscellaneous antiarrhythmic agents?
digitalis
adenosine
magnesium
potassium
117
What drug is a nucleoside that occurs naturally in the body?
adenosine
118
singh-vaughn williams classification class 1B MOA
no effect on APD
-may shorten it
fast dissociation kinetics
119
singh-vaughn williams classification class 1c MOA
drugs have no effect on APD and have slow dissociation
120
singh-vaughn williams classification class 2 MOA
Sympatholytic
-reduce B-adernergic activity in the heart
121
singh-vaughn williams classification class 3 MOA
Manifests as prolongation of the APD
-block the rapid component of the delayed rectifier potassium current IKr
122
singh-vaughn williams classification class 4 MOA
Blockade of the cardiac calcium channel
-slows conduction in regions where action potential upstroke is calcium dependent (SA and AV nodes)
123
What drug shares all four classes of action
amiodarone
124
Sodium channel blocking drugs (class 1)
Procainamide (1a)
Quinidine (1a)
Lidocaine (1b)
Disopyramide (1a)
Flecainide (1c)
125
What is the half life of adenosine in the blood?
less than 10 seconds
126
MOA of adenosine
activation of inward rectifier K= current and inhibition of calcium current
127
What is the result of Adenosine MOA
marked hyperpolarization and suppression of calcium dependent action potentials
128
what is the result of adenosine when administered as a Bolus dose? What does it have less of an effect on?
direct inhibitian of AV nodal conduction
-increase in AV nodal refractory period
Less effect: SA Node
129
what condition/situation is adenosine the drug of choice for?
conversion of Paroxysmal superventricular tachycardia
130
Why is adenosine the top choice for Paroxysmal SVT conversion?
-high efficacy (90-95%)
-short duration of action
131
What is the bolus dose of adenosine administered?
What dose is it followed by?
6mg bolus initial dose
followed by a dose of 12mg (1-2 minutes later)
132
How is adenosine administered?
Rapid IVP with a 20mL saline flush in a line that is a central line or CLOSE peripheral IV line
133
The presence of what makes adenosine less effective?
The presence of adenosine receptor blockers
ex. theophylline, caffeine
134
clinical side effects of adenosine
1. flushing
2. SOB/bronchospasm
3. Chest burning
4. sense of impending doom
Less: headache, HTN, nausea, paresthesisa
135
Toxicity of adenosine in the body?
1.** induction of high grade AV block (short lived). **
2. A-fibb
3. asystole
136
What was magnesium originally used for?
Patients with digitsalis-induced arrhythmias who were hypomagnesemic
137
MOA of Magnesium
influences the Na+/K+ ATPase, sodium channels, calcium channels, certain potassium channels
138
What is conditions/situations is magnesium indicated for?
1. digitalis induced arrhythmias if hypomagnesemia is present
2. some patients with torsades de points (serum mag. can be normal)
139
What is the dosage of Magnesium? How is it administered?
1g (magnesium sulfate)
administered: IV over 20 minutes
repeated as necessary
139
what are the 2 effects of increasing serum potassium?
1. resting potential depolarizing action
2. membrane potential stabilizing action (latter caused by increased potassium permeability)
140
What does hypokalemia result in? (in the heart)
increased risk of early and delayed after depolarizations and ectopic pacemaker activity (in the presence of digitalis)
141
what is the result of Hyperkalemia
Depresses ectopic pacemakers and slows conduction
142
What is required to suppress the SA node?
Hyperkalemia
143
# 8 steps
what is the indepth MOA of Adenosine (adenocard)
1. activates Gi protein
2. inhibition of adenylate cyclase
3. decrease cAMP
4. Deactivation of L-type Ca2+ channels and activation of K+ channels
5. Lowers Ca2+ and increases K+ efflux
6. hyperpolarization
7. transient AV node block (short acting <15 seconds)
8. acute termination of SVT
144
When should the initial dose of adenosine be reduced? what should it be reduced to?
if pt is currently receiving carbamazepine or dipyridamole, has a transplanted heart, or if administered via central line
-3mg bolus followed by saline flush
145
Can potassium effect nerve conduction?
Yes
146
When should adenosine be AVOIDED completely? why?
-Pts with suspected pre-excitation tachycardia
-it may exacerbate the tachycardia via accessory pathway routes.
147
4 contraindications to adenosine
1. pre-excitation syndrome (antidromic AVRT, WPW)
2. AV block
3. Asthma
4. Theophylline or caffeine usage
148
WPW
wolff-parkinson-white syndrome
-congenital heart defect causes arrhythmias
149
