anti-arrhythmic agents Flashcards
(165 cards)
1
Q
arrythmias are classified by
A
site of origin of abnormality
complex on ECG
rhythm
rate
2
Q
what are the 4 mechanisms of arrhythmia production?
A
altered automaticity
delayed after-depolarization
re-entry
conduction block
3
Q
altered automaticity
A
latent pacemaker cells tack over the SA node’s role
4
Q
delayed after depolarization
A
normal action potential of cardiac cell triggers a train of abnormal depolarizations
5
Q
re-entry
A
refractory tissue reactivated repeatedly and rapidly due to unidirectional block which causes abnormal continuous circuit of APs
6
Q
conduction block
A
impulse fail to propagate in non-conducting tissue
7
Q
when do cardiac arrhythmias require treatment
A
when they cannot be corrected by removing the precipitating cause
when hemodynamic stability is compromised
when it predisposes to more serious cardiac arrhythmias or co-morbities
8
Q
name some non-pharmacologic treatments of arrhythmias
A
acute - vagal maneuvers, cardioversion
prophylaxis - radio-frequency catheter ablation, implantable defibrillator
pacing - external, temporary, permanent
9
Q
class I agents - moa
A
block sodium channels
this depresses phase 0 of the fast action potential
= depresses depolarization (decreased rate and slowing conduction velocity)
aka “membrane stabilizing agents”
10
Q
what are class I agents used to treat?
A
SVT, a fib, WPW
11
Q
class IA agents moa
A
intermediate Na channel blocker
slows conduction velocity and pacemaker rate
- decreased depol (phase 0)
- prolonged repol (must block K channels to some degree)
- increased AP duration
direct depressant effects on SA and AV node
12
Q
what do you use class IA agents for
A
atrial and ventricular arrhythmias
13
Q
name the class IA agents
A
quinimide (prototype) - no longer available
procainamide
disopyramide (Norpace)
14
Q
why aren’t class IA drugs commonly used?
A
they cause toxicity and may precipitate heart failure
15
Q
what is disopyramide
A
PO agent that suppresses atrial and ventricular tachyarrhythmias
16
Q
what are the negative side effects of disopyramide
A
myocardial depressant effects and can precipitate CHF and hypotension
17
Q
when do you use procainamide
A
used in the treatment of vent tachycardias (less effective with atrial)
was once part of ACLS algorithm
18
Q
dose of procainamide
A
loading: 100 mg IV q5min until rate controlled (MAX = 15 mg/kg)
then
infusion: 2-6 mg/min
19
Q
side effects of procainamide
A
myocardial depression leading to hypotension
syndrome that resembles lupus
20
Q
therapeutic levels of procainamide
A
= 4-8 mcg/ml
21
Q
how protein bound is procainamide
A
15%
22
Q
what is the half life of procainamide
A
2h
23
Q
what are the class IC agents
A
flecainide (prototype)
propafenone (PO)
24
Q
class IC moa
A
slow Na+ channel blocker (slow dissociation) so does not vary much with cardiac cycle
causes potent decrease of depolarization rate (phase 0) and decreased conduction rate with increased AP
markedly inhibits conduction through His-Purkinje system
25
Flecainamide uses and side effects
effective in treatment of suppressing PVS and ventricular tach, also atrial tach, WPW (reentry syndrome)
PO
has pro-arrhythmic side effects **can cause sudden death with v-fib
26
propafenone uses and side effects
suppression of ventricular and atrial tachyarrhythmias
PO
has pro-arrhythmic side effects - can cause torsades and sudden death with vfib
27
what are the class IB agents
lidocaine (prototype)
mexiletine (PO)
phenytoin
28
class IB moa
fast Na channel blocker = fast dissociation
alters AP by inhibiting Na ion influx via rapidly binding to and blocking sodium channels
produces little effect on max velocity depol rate, but shortens AP duration adn shortens refractory period
decreases automaticity
29
lidocaine use and SE
used in treatment of ventricular arrhythmias
particularly effective with suppression reentry rhythm: V tach, v fib, PVCs
don't use to treat v fib after acute MI because it increases mortality d/t bradyarrhythmias
30
dose of lidocaine
IVP: 1-1.5 mg/kg
gtt: 1-4 mg/min (max dose 3 mg/kg)
31
how protein bound is lidocaine
50%
32
how is lidocaine metabolized
hepatic metabolism - cyp450
- active metabolite prolongs elimination half time
extensive first pass metabolism when taken PO
33
what can alter metabolism of lidocaine
impaired by
- drugs such as cimetidine and propanolol
- CHF, acute MI, liver dysfunction
- General anesthesia
can be induced by barbs, phenytoin, or rifampin
34
describe lidocaine elimination
10% eliminated renally
35
adverse effects of lidocaine
hypotension, bradycardia, seizures, cns depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment pre-existing neuromuscular blockade
36
what is mexiletine used for
chronic suppression of ventricular tachyarrhythmias - PO agent
37
dose of mexiletine
150-200 mg Q8H
38
why can mexilitine be taken orally and lidocaine cannot
amine side group allows for PO admin because it avoids first pass metabolism
39
phenytoin uses
effects resemble lidocaine
used in suppression of ventricular arrhythmias associated with digitalis toxicity
can also be used for other ventricular tachycardias or torsades
40
how is phenytoin given
IV in NS
will precipitate in D5W
can be painful in peripheral IV
41
dose of phenytoin
1.5 mg/kg every 5 minutes up to 10-15 mg/kg
42
therapeutic blood levels of phenytoin
10-18 mcg/ml
43
how is phenytoin metabolized
by the liver
44
how is phenytoin excreted
in the urine
45
what is the elimination half time of phenytoin
24 hours
46
what are the adverse effects of phenytoin
CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, ataxia, slurred speech, severe hypotension with rapid admin
47
class II moa
beta-adrenergic agonists
depress spontaneous phase 4 depolarization resulting in SA node discharge decrease = slowing of heart rate and decreased mvo2
48
class II moa
beta-adrenergic agonists
depress spontaneous phase 4 depolarization resulting in SA node discharge decrease = slowing of heart rate and decreased mvo2
slows speed of conduction of cardiac impulses through atrial tissues and AV node resulting in prolongation of PR interval, increased duration of AP, decrease automaticity
prevents catecholamine binding to beta receptors
49
what are class II agents used for
treats SVT, atrial and ventricular arrhythmias
suppress and treat ventricular dysrhythmias during MI and reperfusion
treats tachyarrhythmias secondary to digoxin toxicity and SVT (afib/aflutter)
50
What are the class II agents
propanolol (prototype)
esmolol
metoprolol
51
what is the selectivity of propanolol
non-selective
52
what is the use of propanolol
to prevent reoccurence of tachyarrhythmia, both supraventricular and ventricular precipitated by SYMPATHETIC STIMULATION
53
what is the onset of propanolol
2-5 minutes
54
when would you expect peak effects of propanolol
10-15 minutes after given
55
what is the duration of propanolol
3-4 hours
56
what is the elimination half time of propanolol
2-4 hours
57
what are the cardiac effects of propanolol
decreased HR, contractility, and CO
increased PVR (bronchoconstriction d/t beta2 block), coronary vascular resistance
Decreased MVO2 (demand)
58
what is the selectivity of metoprolol
beta 1 selective
59
dose of metoprolol
5mg over 5 min
max dose 15 mg over 20 min
60
onset of metop
2.5 min
61
duration/half-life of metop
3-4 hours
62
how is metop metabolized
liver
63
when do you use metop
mild CHF
64
what is the selectivity of esmolol
selective for beta 1
65
what is the dose of esmolol
0.5 mg/kg bolus over 1 min, then 50-300 mcg/kg/min
66
what is the duration of esmolol
<10 mins = quick acting, short acting
67
how is esmolol metabolized
hydrolyzed by plasma esterases
68
in small doses, how does esmolol effect HR and BP
effects HR (decrease) without significantly decreasing BP
69
class III agents moa
block potassium channels which
- prolongs cardiac depolarization (cells don't start to repol because VGKs dont open)
- increased AP duration (because K can't efflux to bring cells back to baseline)
- lengthening repolarization (same as above)
PROPORTION OF CARDIAC CYCLE WHERE CELLS ARE EXCITABLE IS DECREASED = aka longer time in refractory aka cell isn't susceptible to AP trigger
70
class III agent uses
treat supraventricular and ventricular arrhythmias
preventative in patients who have survived sudden cardiac death who are not candidates for ICD
control rhythm in Afib
- this is given prophylactically in cardiac surgery patients because there is a high incidence of afib
71
what is a negative ekg change caused by class III agents
prolongation of QT interval can lead to torsades
72
what are the class III agents
```
amiodarone (prototype)
dronedarone
ibutilide
dofetilide (PO)
sotalol
```
73
amiodarone moa
```
characterized as class III but also has I, II, and IV properties
- aka it blocks K, Na, and Ca channels and its a beta agonist
```
however, it works primarily in phase II and III as a k channel blocker
74
uses of amiodarone
prophylaxis or acute treatment for atrial and ventricular arrhythmias (refractory SVT, refractory VT/VF, AF)
1st line drug for VT/VF when resistant to electrical defibrillation
"one of the most effective drugs at preventing arrhythmias in patients with HF"
75
dose of amiodarone
bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg
then
1 mg/hr for 6 hours
then
0.5 mg/hr for 18 hours
76
what is the elimination half life
29 days - prolonged
77
how is amiodarone metabolized
hepatic with active metabolite
78
how is amiodarone excreted
biliary/intestinal excretion
79
what is the therapeutic plasma level for amio
1.0-3.5 mcg/ml
80
is amio protein bound?
yes 96%, extensively
81
describe the volume of distribution of amiodarone
large
82
amiodarone adverse effects
```
PULM TOXICITY (lung fibrosis d/t free O2 radicals in drugs)
pulm edema
ARDS
abnormal LFT
photosensitive rash
grey/blue skin discoloration
thyroid abnormalities
corneal deposits
TORSADES (arrhythmic effects)
HEART BLOCK
HYPOTENSION
sleep disturbances
CYP450 INHIBITOR!!!!!!
```
83
sotalol moa
```
primarily class III drug with some class II action
aka K channel blocker with some nonselective beta agonism included
```
84
uses of sotalol
used to treat severe sustained v tach and v fib, to prevent reoccurrence of tachyarrhythmias (especially afib and aflutter)
85
side effects of sotalol
```
prolonged qt interval
bradycardia
myocardial depression
fatigue
dyspnea
av block
```
86
what is a patient population you should use caution with when giving sotalol (think respiratory)
asthma because non selective beta antagonism action
87
how is sotalol excreted
urine
88
dofetilide and ibutilide uses and main SE
class III
used for conversion of afib or aflutter to NSR
used for maintenance of SR after afib or conversion of afib to sinus
SE: pro-arrhythmic d/t prolongation of QT interval
89
name the class IV calcium channel blockers
verapamil
diltiazem
nifedipine
90
where are calcium ion channels?
```
skeletal muscle cell membrane
VSMC
cardiac muscle
mesenteric muscle
neurons
glandular cells
coagulation
```
91
calcium channel blockers moa
block L-type channels selectively to interfere with inward calcium ion movement across myocardial and vascular smooth muscle cells
92
structure and area of action of verapamil
and moa at channel
phenyl-alkyl-amine at AV node
intracellular pore blocking of channel at binding site
93
structure and area of action of diltiazem
and moa
benzothiazepine at AV node
mechanism unclear
94
structure and area of action of nifedopine
and moa
1, 4-dihydropyridine at arterial beds
extracellular allosteric modulation of channel at binding site
95
structure and importance of L-type calcium channel
5 subunits
alpha 1 is the central part of channel and provides main path for Ca2+ to enter
this is a slow channel
important in determining vascular tone and cardiac contractility
96
vascular uses of calcium channel blockers
```
angina
systemic hypertension
pulmonary hypertension
cerebral arterial spasm
raynauds
migraine
```
ca channel blockers dilate coronary arteries and decrease contractility of VSMC
97
non-vascular uses of calcium channel blockers
bronchial asthma
esophageal spasm
dysmenorrhea
premature labor (prevention)
98
effects of ca channel blockers
decreased contractility
decreased HR
decreased activity of SA node
decreased rate of conduction of impulses via AV node
vascular smooth muscle relaxation = decreased SVR and BP
- arterial > venous
decreased mvo2 (demand)
99
uses for calcium channel blockers
treatment of SVT, ventricular rate control in afib and aflutter
prevention of reoccurrence of SVT
NOT used in ventricular arrhythmias
100
verapamil structure highlights
phenylakylamine
synthetic derivative of papaverine
levoisomer is specific for the slow calcium channel
101
moa verapamil
depresses the AV node
negative chronotropic effects on SA node aka decreased HR
negative inotropic effects on myocardial muscle aka decreased contractility
moderate vasodilation on coronary as well as systemic arteries
102
clinical uses for verapamil
```
SVT
vasospastic angina pectoris
HTN
hypertrophic cardiomyopathy
maternal and fetal tachydysrhythmias
premature onset of labor
```
103
protein binding of verapamil
highly protein bound - presence of other agents that are protein bound such as lidocaine, diazepam, propanolol increase its activity
104
absorption of verapamil
orally almost completely absorbed with extensive hepatic metabolism and almost none of the drug appears unchanged in the urine
105
oral and IV peak of verapamil
```
PO = 30-45 minutes
IV = 15 minutes
```
106
elimination half time of verapamil
6-12 hours
6-8 on later slide?
107
dose of verapamil
2.5-10mg IV over 1-3 minutes (max dose 20mg)
| continuous gtt 5 mcg/kg/min
108
what med is iv verapamil contraindicated with
beta blockers because it can cause a heart block
109
how is verapamil metabolized
hepatic with active metabolite norverapamil
110
how is verapamil excreted
in the urine and bile
111
side effects of verapamil
myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMBDs
112
site of action of diltiazem
AV node is prinicple site of action
113
what is the first line treatment for SVTs
diltiazem
114
what is the relative potency of diltiazem in comparison to the other class IV calcium channel blockers
intermediate between verapamil and nifedipine
115
what is the extent of CV depressant effects of diltiazem
minimal
116
clinical uses of diltiazem
```
SVT***
vasospastic angina pectoris
HTN
hypertrophic cardiomyopathy
maternal and fetal cardiac dysrhythmias
```
117
dose of diltiazem
0.25-0.35 mg/kg over 2 minutes, can repeat in 15 minutes
infusion = 10 mg/h
118
oral onset and peak of diltiazem
15 minutes peaks in 30
119
protein binding of diltiazem
70-80%
120
excretion of diltiazem
bile and urine
121
what patients would need a decrease in dose of verapamil
liver disease
122
clinical uses of nifedipine
angina pectoris
123
primary site of action of nifedipine
peripheral arterioles
124
clinical effect on SA/AV node?
little to no effect
125
what is a HR concern for nifedipine
reflex tachycardia
126
what patients are at risk for myocardial depression with nefedipine?
patients with LV dysfunction or those on beta blockers
127
what are the routes of admin for nifedipine
IV, PO, sublingual
128
oral onset and peak
onset 20 minutes
| peak 60-90 minutes
129
protein binding of nifedipine
90% protein bound
130
metabolism of nifedipine
hepatic
131
excretion of nifedipine
urine
132
elimination half time of nifedipine
3-7 hours
133
side effects of calcium channel blockers
cancer with long term use
cardiac problems
bleeding d/t interference with platelet function
constipation
vertigo, HA, flushing, hypotension, paresthesias, muscle wekaness
can induce renal dysfunction
134
what is the drug interaction of calcium channel blockers with inhalational agents
myocardial depression
135
what is the drug interaction of calcium channel blockers with NMBDs
can potentiate blocks
136
what is the drug interaction of calcium channel blockers with beta blockers
risk for heart block - particularly with verapamil
137
what is the drug interaction of calcium channel blockers with local anesthetics
verapamil increases risk of LA toxicity
138
what is the drug interaction of calcium channel blockers with dantrolene
verapamil and dantrolene can cause hyperkalemia due to slowing of inward movement of K ions which can result in cardiac collapse
139
what is the drug interaction of calcium channel blockers with digoxin
can increase the plasma concentration of digoxin by decreasing its plasma clearance
140
what is the drug interaction of calcium channel blockers with H2 antagonists
ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCBs
141
how do you reverse calcium channel blocker toxicity?
IV administration of calcium or dopamine
142
why are patients on CCB a bleeding risk
they interfere with calcium mediated platelet function
143
what can happen with abrupt d/c of CCBs
coronary vasospasm
144
adenosine moa
binds to A1 purine nucleotide receptors
- activates adenosine receptors to open K channels and increase K currents
- slows AV nodal conduction
145
what is adenosine used for
acute only to terminate SVT or for diagnosis of VT
146
dose of adenosine
6mg iv rapid bolus
| repeated if necessary after 3 minutes, 6-12 mg iv rapid bolus
147
how affective is the first dose of adenosine vs the second dose
effective on first dose 60%
| effective on second dose 90%
148
half life of adenosine
<10 seconds
149
elimination of adenosine
via plasma and endothelial cell enzymes
150
side effects of adenosine
excessive AV or SA nodal inhibition, facial flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm
151
adenosine is contraindicated in which patients
```
asthma (causes bronchospasm)
heart block (slows AV conduction)
```
152
digoxin mechanism of action
comes from foxblood plant - cardiac glycoside
increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses through AV node by increasing refractory period
decreases HR, preload, and afterload
153
digoxin uses
for management of afib/flutter (controls ventricular rate) especially with impaired heart function
used to treat chf because it is a positive inotrope
154
dose of digoxin
0.5-1 mg in divided doses over 12-24 hours
155
onset of action of digoxin
30-60 minutes
156
half life of digoxin
36 hours
157
describe the therapeutic index of digoxin
narrow
0.5-1.2 ng/ml
158
describe the protein binding of digoxin
weak
159
how is digoxin excreted
90% by kidneys
160
considerations for elderly or those with renal impairment?
reduce dose and frequently check levels
161
adverse effects of digoxin
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
- potentiated by hypomagnesemia and hypokalemia
162
how to treat digoxin toxicity
phenytoin for ventricular arrhythmias
pacing
atropine
163
magnesium moa
works at sodium, potassium, and calcium channels
164
when do you use magnesium
torsades
165
dose of magnesium
1g IV over 20 minutes, can be repeated
