Exam 2 Week 1- Anti-arrhythmic Agents Flashcards
1
Q
Phase 0 (Cardiac Cell)
A
rapid depolarization (fast sodium channels open; fast inward flow of Na+)
2
Q
Phase 1 (Cardiac Cell)
A
beginning of repolarization (sodium channels close)
3
Q
Phase 2 (Cardiac Cell)
A
plateau (slow calcium channels open; slow inflow of Ca2+)
4
Q
Phase 3 (Cardiac Cell)
A
repolarization (calcium channels close; potassium channels open; slow outward K current)
5
Q
Phase 4 (Cardiac Cell)
A
pacemaker potential; returning to resting membrane potentials
6
Q
Refractory period (Cardiac Cell)
A
phases 1-3
periods of repolarization
7
Q
Phase 0 (SA/AV Node)
A
upstroke
critical firing threshold (-40mV)
slower and Ca2+ mediated
8
Q
Phase 3 (SA/AV Node)
A
repolarization
inactivation of Ca2+ and Na+ channels
activation of K channels
9
Q
Phase 4 (SA/AV Node)
A
gradual depolarization
slow inward Na and Ca2 currents
10
Q
What node is the cardiac pacemaker?
A
Sino-atrial
11
Q
Normal sinus rhythm is
A
60-100bpm
12
Q
Which node conducts more slowly then the SA?
A
AV node
13
Q
Which node conducts faster then the AV node?
A
Purkinje fibers
14
Q
P wave indicates
A
Atrial depolarization
15
Q
QRS complex represents
A
ventricular depolarization
16
Q
T wave represents
A
ventricular repolarization
17
Q
What is an arrhythmia
A
is the disturbance in the electrical activity of the heart
18
Q
Classification of arrhythmia
A
site of origin of abnormality (atrial/junctional/ventricular)
complexes on ECG
Heart Rhythm (regular/irregular)
Heart rate is increased or decreased
19
Q
Mechanisms of arrhythmia production
A
Altered automaticity
delayed after-depolarization
re-entry
conduction block
20
Q
Altered automaticity
A
latent pacemarker cells take over the SA node’s role; escape beats
21
Q
Delayed after-depolarization
A
normal action potential of cardiac cell triggers
22
Q
Re-entry
A
refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit
23
Q
Conduction Block
A
impulse fail to propagate in non-conducting tissue
24
Q
Supraventricular Drugs
A
adenosine IV
digoxin
verapamil
25
Stress Induced Drugs
Class 2
| beta blockers, propanolol, atenolol, sotalol
26
Sinus Bradycardia drugs
atropine IV
27
Ventricular and supra-ventricular drugs
Class 3- amiodarone, sotalol
Class 1A- procainamide and disopyramide
Class 1C- flecanide, propafenone
28
Ventricular Drugs
class 1B- lidocaine, mexlietine
29
Factors underlying cardiac arrhythmias
```
arterial hypoxemia
electrolyte imbalance
acid-base abnormalities
myocardial ischemia
altered sympathetic nervous system activity
bradycardia
administration of certain drugs
enlargement of a failing ventricle
```
30
When do cardiac arrhythmias require treatment?
they cannot be corrected by the removing the precipitating cause
hemodynamic stability is compromised
the disturbance predisposed to more serious cardiac arrhythmias or co-morbidities
31
Non-pharmacological treatment
acute: vagal manuevers/cardioversion
Prophylaxis: radiofrequency catheter ablation/ implantable defibrillator
Pacing: External, temporary, permanent
32
What anti-arrhythmic agents utilized for?
used to prevent, suppress or treat a disturbance in cardiac rhythm
33
Class 1 Anti-arrhythmic Drug Class
Sodium Channel Blockers/Phase 0
34
Class 2 Anti-arrhythmic Drug Class
Beta adrenergic blocker/ Phase 4
35
Class 3: Anti-arrhythmic Drug Class
Potassium Channel Blockers
36
Class 4: Anti-arrhythmic Drug Class
Calcium Channel blockers
37
Class 5: Anti-arrhythmic Drug Class
Unclassified drugs
38
Electrophysiologic Effect of Class 1 Anti-Arrhythmic Drugs
depression of phase 0 depolarization (block of sodium channels)
Results in decreases in action potential propogation (decrease in depolarization rate) and slowing conduction velocity
membrane stabilizing agents
Binds to open or inactive gate best, not resting state
39
Electrophysiologic Effect of Class 1A Anti-Arrhythmic Drugs
Moderate depression and prolonged repolarization
40
Electrophysiologic Effect of Class 1B Anti-Arrhythmic Drugs
weak depression and shortened repolarization
41
Electrophysiologic Effect of Class 1C Anti-Arrhythmic Drugs
strong depression with little effect on repolarization
42
Electrophysiologic Effect of Class 2 Anti-Arrhythmic Drugs
Beta adrengeric blocking effects
43
Electrophysiologic Effect of Class 3 Anti-Arrhythmic Drugs
prolongs repolarization (blocks potassium channels)
44
Electrophysiologic Effect of Class 4 Anti-Arrhythmic Drugs
Calcium channel-blocking effects
45
Other Anti-arrhythmic Drugs
Adenosine, adenosine triphosphate, digoxin, and atropine
46
Class 1A Drugs
quindine, procainamide, disopyramide
47
Class 1B Drugs
lidocaine, mexiletine, phenytoin, tocainide
48
Class 1C drugs
flecainide, propafenone, moricizine
49
Class 2 drugs
esmolol, propanolol, metoproplol, timolol, pindolol, atenolol, acebutuolol, nadolol, carvedilol
50
Class 3 drugs
amiodarone, bretylium, sotalol, ibutilide, dafetilide
51
Class 4 Drugs
verampil, dilitiazem
52
Class 1 Agents treat
SVT, AF, WPW
53
Class 1A Agents
slow conduction velocity and pacemaker rate
intermediate sodium channel blocker (immediate dissociation)
direct depressant effects on SA and AV node (decrease automaticity)
Decreased depolarization rate (phase 0)
prolonged repolarization
Increased AP duration
Used for atrial and ventricular arrhythmias
Eliminated by hepatic metabolism
Implication in reversible lupus like syndrome
increases QT duration
54
Disopyramide
suppresses atrial and ventricular tachyarrhythmias
oral agent
has significant myocardial depressant effects and can precipitate congestive HF and hypotension
55
Procainamide
used in treatment of ventricular tachyarrhythmias (less effective with atrial)
15% protein bound
2 hour elimination time
56
Procainamide Dose
Loading 100mg IV Q5mins until rate controlled
max: 15mg/kg
Infusion 2-6mg/min
57
Procainamide Side Effects
myocardial depression leading to hypotension
syndrome that resembles lupus erythematous
Check blood levels 4-8mcg/ml
58
Class 1C Agents are good for
Block fast Na+ channels but slow dissociation
| Good for PVC and Vtach but better for atrial arrhythmias like WPW
59
Flecainide
effective in the treatment of suppressing ventricular PVCs and ventricular tachycardia; also atrial tachyarrthymias; WPW
oral agent
has pro-arrhythmic side effects
60
Propafenone
suppression of ventricular and atrial tachyarrhythmias
oral agent
has pro-arrhythmic side effects
61
Class 1C Agents MOA
Slow sodium channel blocker (slow dissociation) so does not vary much during the cardiac cycle
potent decrease of depolarization rate phase 0 and decreased conduction rate, with increased AP
marked inhibit conduction through the his purkinje system
62
Class 1B Agents MOA
fast Na+ channel blocker (fast dissociation)
alters the action potential by inhibiting sodium ion influx via rapidly binding to an blocking sodium channels (fast)
produces little effect on maximum velocity depolarization rate, but shortens AP duration and shortens refractory period
decreases automaticity
63
Lidocaine
used in the treatment of ventricular arrhythmias
(no longer recommended for preventing ventricular fibrillation after acute MI)
Particularly effective in suppression re-entry rhythms: ventricular tachycardia, fibrillation, PVCs
64
Pharmokinetics of Lidocaine
Dose: 1-1.5 mg/kg IV
Infusion 1-4 mg/min (max dose 3mg/kg)
50% protein binding
Hepatic Metabolism (active metabolism, prolongs elimination)
Metabolism affected by CYP inhibitors and inducers
10% renal elimination
extensive first pass
NOT a pro-arrhythmic b/c dissociates too quickly
65
Adverse Effects of Lidocaine
hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment pre-existing neuromuscular blockade
66
Mexilentine
oral agent
chronic suppression of ventricular cardiac tachyarrhythmias
cardiac clearance required
150-200mg Q8H
amine side group that allows to be adminstered oral
Can also be seen in neuropathetic pain
67
Phenytoin
```
effects resemble lidocaine
class 1b agent
used in suppression of ventricuar arrhythmias associated withe digitalis toxicity
can also be used with other ventricular tachycardias or torsades de pointes
given IV (must be saline)
```
68
dose of phenytoin
1.5mg/kg IV every 5 mins, up to 10-15 mg/kg
69
Therapeutic Phenytoin Blood level
10-18 mcg/ml
70
Pharmacokinetics of Phenytoin
metabolized in the liver
excreted in urine
elimination 1/2 time @ 24 hours
71
Phenytoin adverse effects
CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea
SJS
72
Class 2 Agents MOA
drug induced slowing of the heart rate with resulting decreases in myocardial oxygen requirements is desirable in patients with CAD
slow speed of conduction of cardiac impulses through atrial tissues and AV node resulting in prolongation of the PR interval on EKG, increased duration of the action potential in atria
decreased automaticity
prevents catecholamine binding to beta receptors
slowing of heart rate
decrease myocardial oxygen requirements
73
Class 2 agents are used to treat
SVT, atrial and ventricular arrhythmias
used to suppress and treat ventricular dysrhythmias during MI and reperfusion
to treat tachyarrhythmias secondary to digoxin toxicity, and SVT (atrial fibrillation or flutter)
74
Propranolol
prototype
beta adrenergic antagonist
used to prevent reoccurance of tachyarrhythmias, both supraventricular and ventricular precipated by sympathetic stimulation
75
Onset of propanolol
2-5 minutes
76
Peak effect of Propanolol
10-15 minutes
77
Duration of Propanolol
3-4 hours
78
Elimination half time of propanolol
2-4 hours
79
Cardiac Effects of Propanolol
decreased HR, contractility, CO, increased PVR, coronary vascular resistance, however oxygen demand lowered
80
Metoprolol
Beta adrenergic Antagonist (selective B1)
81
Dose of metoprolol
5 mg IV of 5 mins
| max dose: 15 mg over 20 minutes
82
Onset of metoprolol
2.5 minutes
83
1/2 life of metoprolol
3-4 hours
84
Metoprolol is metabolized in
liver
85
Is metoprolol okay to used in CHF?
Only mild cases
86
Esmolol
Beta adrenergic antagonist (selective B1)
| Effects without decreasing BP significantly in small doses
87
Dose of Esmolol
0.5mg/kg IV bolus over 1 min, then 50-300 mcg/kg/min
88
Duration of Esmolol
less then 10 minutes
89
Class 3 Agents MOA
K ion channels blocked causes prolongation of cardiac depolarization and increasing action potential duration, and lengthening repolarization
decreases proportion of the cardiac cycle during which myocardial cells are excitable and thus susceptible to a triggering event
90
Class 3 agents treat
supraventricular and ventricular arrhythmias
can prolong QT interval and develop torsades
prophylaxis in cardiac surgery patients d/t high incidence of afib
preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
control rhythm in afib
91
amiodarone
potassium, sodium, calcium channel blocker and alpha and beta adrenergic antagonist
used for prophylaxis or acute treatment in the treatment of atrial and ventricular arrhythmias (refactory SVT, refractory VT/VF, AF)
1st line drug VT/VF when resistant to electrical defibrillation
92
Dose of amiodarone
bolus 150-300 mg IV over 2-5 minutes, up to 5mg/kg then 1mg/hr x6 hours then 0.5mg/hr x 18 hrs
93
Pharmacokinetics of Amiodarone
```
prolonged elimination half-time (29 days)
hepatic metabolism, active metabolite
biliary/intestinal excretion
extensive protein binding 96%
large volume of distribution
```
94
Therapeutic Plasma Level of Amiodarone
1-3.5ug/ml
95
Adverse effects of Amiodarone
```
pulmonary toxicity
pulmonary edema
ARDs
photosensitivity rashes
grey/blue discolouration of skin
thyroid abnormalities
corneal deposits
CNS/GI disturbances
pro-arrhythmic effects (torsades de pointes)
heart block
hypotension
sleep disturbances
abnormal LFT 20%
inhibits hepatic P450
```
96
Sotalol
Class 2 and 3 antiarrhythmic
beta adrenergic antagonist (nonselective) and potassium channel blocker
used to treat severe sustained ventricular tachycardia and ventricular fibrillation; to prevent reoccurance of tachyarrhythmias, especially aflutter and afib
excreted in urine
97
Side effects of sotalol
prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block,
caution in asthmatics
98
Dofetilide and Ibutilide
class 3 antirrhythmics
used for conversion of afib or aflutter to NSR
used for maintenance of sinus rhythm after Afib or conversion of Afib to sinus
pro-arrhythmic
99
Calcium Channel Blockers are located in
```
cell membranes of skeletal musle
vascular smooth muscle
cardiac muscle
mesenteric muscle
neurons
glandular cells
```
100
Calcium Channel blockers bind to
the receptor on voltage gated calcium ions maintaining the channels in an inactive or closed state
101
Calcium channel blockers
selectively interfere with inward calcium ion movement across myocardial and vascular smooth muscle cells
102
Calcium channel blockers are classified by:
phenyl-alkyl amines- AV node (verapamil)
Benzothiazepines-AV (diltiazem)
1,4 dyhydropyrindines-arterial beds (nifedopine)
103
Vascular Uses of CCBs
```
angina
systemic hypertension
pulmonary hypertension
cerebral arterial spasm
raynaud's disease
migraine
```
104
Nonvascular Uses of CCBs
bronchial asthma
esophageal spasm
dysmenorrhea
premature labor
105
MOA of CCB
primary site AV node
blocks slow calcium channels, which decreases conduction through AV node and shortens phase 2 of the action potential in ventricular myocytes
contracility of the heart decreases
106
L type calcium channel is important in
determining vascular tone and cardiac contractility
| decreased Ca keeps intracellular Ca+ low
107
CCB effects
decreased contractility
decrease HR
decreased activity of SA node
decreased rate of conduction of impulses via AV node
vascular smooth muscle relxation: decrease SVR and BP (arterial> venous)
108
CCB is used to
used in the treatment of SVT and ventricular rate control in Afib and Aflutter
Used to prevent reoccurrence of SVT
109
Verapamil
synthetic derivative of papaverine
Primary site of action is the AV node
Depresses the AV node
negative chronotropic effect on SA node
110
Clinical Uses of CCB
SVT, vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal and fetal tachydysrhymthmias
premature onset of labor
111
Pharmacokinetic Verapamil
highly protein bound (presence of other agents such as lidocaine, diazepam, propranolol increase its activity)
Hepatic first pass metabolism and almost none of the drug appears unchanged in the urine
active metabolite, norverampil
excreted in urine and bile
112
Verapamil Peaks
Oral: 30-45 minutes
IV: 15 minutes
113
Elimination 1/2 Time of Verapamil
6-8hours
114
Dose of Verapamil
2.5-10mg IV over 1-3 minutes (max dose 20 mg)
| Continuous gtt: 5 ug/kg/min
115
Do not mix verapamil with
a beta blocker
116
Verapamil Side Effects
myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMB
117
Diltiazem is a
benzothiazepines derviative
118
Site of Action of Diltiazem
```
AV node
1st line treatment of SVT
HTN
intermediate potency between verapamil and nifedipine
minimal CV depressant effects
```
119
Clinical Uses of Diltiazem
similar to verapamil
SVT
vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal and fetal tachydysrhymthmias
premature onset of labor
120
Dose of Diltiazem
0.25-0.35mg/kg over 2 minutes can repeat in 15 minutes
| IV infusion 10mg/h
121
Forms of Diltiazem
PO or IV
122
Pharmacokinetics of Diltiazem
oral onset 15 minute
peaks in 30 minutes
70-80% protein bound/ excreted in the bile and urine (inactive metabolite)
Elimination 1/2 time: 4-6 hours
Liver disease may require a decrease dose
123
Side effects of Diltiazem
myocardial demand
decrease HTN
constipation
bradycardia
124
Nifedipine is a
dihydropyridine derviative
125
Clinical uses of Nifedipine
angina pectoris
126
Primary site of action of Nifedipine
peripheral arterioles
coronary and peripheral vasodilator properties then verpamil
little to no effect on SA or AV node
decrease SVR, BP
reflex tachycardia
can produce myocardial depression in patients with LV dysfunction or on beta blockers
127
Routes of Nifedipine
IV oral Sublingual
128
Pharmacokinetics of Oral Nifedipine
effects in 20 minutes
peaks in 60-90 minutes
90% protein bound/ hepatic metabolism, excreted in urine
Elimination 1/2 life is 3-7 hours
129
Side effects of Nifedipine
cancer
cardiac problems
bleeding (prolonged)
GI constipation
130
CCB Drug interactions Cause
myocardial depression and vasodilation with inhalation agents
can potentiate NMB
interact with calcium mediated platelet function
131
Verapamil and BB
potentiate HR block
132
Verapamil increase the risk
of local anesthetic toxicity
133
Verapamil and Dantrolene can cause
hyperkalemia due to slowing of inwawrd movement of K ions can result in cardiac collapse
134
Digoxin and CCBs
increase the plasma concentration of digoxin by decreasing its plasma clearance
135
H2 antagonist and CCBs
ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCB
136
Toxicity of CCB
may be reversed with IV administration of calcium or dopamine
137
Side Effects of CCB
```
vertigo
headache
flushing
hypotension
paresthesias
muscle weakness
can induce renal dysfunction
coronary vasospasm with abrupt discontinuation
```
138
Other CCBs
```
clevidipine
dihydropyridine
potent vasodilator
broken down by plasma esterases
4-6 mg/ hr IV. start at 1-2 mg/hr and titrate up to 32mg/hg
```
139
Adenosine
binds to A1 purine nucleotide receptors (activated adenosine receptors to open K+ channels and increase K+ currents
slows AV nodal conduction
used for acute Rx only
used for termination of SVT /diagnosis of VT
140
Dose of Adenosine
6mg IV bolus, rapid
| repeat if necessary after 3 minutes, 6-12 mg IV
141
T1/2 of Adenosine
<10 seconds
142
how is adenosine eliminated?
plasma and vascular endothelial cell enzymes
143
Side effects of adenosine
excessive AV or SA nodal inhibition, facial flushing, headache, dyspnea, chest discomfort, nausea, bronchospasm
144
Digoxin
cardiac glycoside
increases vagal activity thus decreasing activity of SA node and prolongs conduction of impulses through the AV node
Decreases HR, preload and afterload
slows AV conduction by increasing AV node refractory period
positive inotrope- used to treat CHF
145
Pharmacokinetics of Digoxin
```
used for management of atrial fibrillation or flutter (controls ventricular rate), especialy withe impaired heart function
narrow therapeutic index
levels: 0.5-1.2ng/ml
Week protein binding
90% excreted by kidneys
reduce dose in elderly/ renal impairment
```
146
Dose of Digoxin
0.5-1mg divided into doses of 12-24 hours
147
Onset of action of Digoxin
30-60 minutes
148
T1/2 of digoxin
36 hours
149
Adverse effects of Digoxin
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
potentiated by hypokalemia and hypomagnesemia
150
Digoxin Toxcity treatment
phenytoin for ventricular arrthymias
pacing
atropine
151
Magnesium
works at sodium, potassium, calcium channels
can be used with torsaded de pointes
dose 1 gm IV over 20 minutes; can be repeated
152
Atropine
```
muscarinic receptor antagonist
unstable bradyarrhythmias
0.4-1mg and repeat as neccessary
metabolized by liver
onset less then 1 mint
DOA 30-60 minutes
caution dosing < 0.4 mg-> paradoxical response
```
