PHARMACOLOGYOFANTIARRHYTHMICS Flashcards
1
Q
Class Ia: Na+Channel Blockers
A
Disopyramide(Norpace)
Quinidine
Procainamide*
double quarter pounder
2
Q
Class Ib: Na+Channel Blockers
A
Lidocaine(Xylocaine)*
Mexiletine
Tocainide
lettuce may tomato
3
Q
Class Ic: Na+Channel Blockers
A
Moricizine
Flecainide(Tambocor)
Propafenone(Rythmol)
more fries please
4
Q
Class II: β-Adrenergic Receptor Blockers
A
Esmolol(Brevibloc)*
Metoprolol (Lopressor, Toprol XL)*
Propranolol (Inderal)
5
Q
Class III: K+Channel Blockers
A
Amiodarone(Cordarone)*
Bretylium
Dofetilide(Tikosyn)
Ibutilide
Sotalol(Betapace)
a big dog is scary
6
Q
Class IV: Ca2+Channel Blockers
A
Verapamil(Calan)*
Diltiazem (Cardizem)
7
Q
Other ACLS Drugs
A
Adenosine
Atropine
Anticoagulants
Digoxin
MgSO4
Naloxone (Narcan)
Vasopressors
8
Q
AV node slows done bc
A
calcium channels
9
Q
TRANSMEMBRANE POTENTIAL
A
Resting membrane potential determined by concentrations of ions
Sodium (Na+), Potassium (K+), Calcium (Ca2+), Chloride (Cl-)
Ions unable to cross lipid membrane
Electrical gradient
-90 mV inside, 0 mV outside
10
Q
Na flow
A
chemical and electrical flow inside
11
Q
K flow
A
electrical in and chemical out
12
Q
CELL MEMBRANE
A
Depolarization opens the activation (m) gates
If inactivation (h) gates have not already closed, the channels are open and activated
Opening brief; open (m) gates very quickly followed by closure of (h) gates and channel inactivation
13
Q
na channel blockers are state dependant and bind the
A
activated and inactivated states.
binds when activated or extending inactivated state so both are prolonging the ap duration and not alowing the na channel to open and fire again
14
Q
Cell depolarization
Phase - 0
A
rapid depolarization
abrupt increase in na permeability
15
Q
Cell depolarization
Phase - 1
A
brief repolarization
transient k efflux
16
Q
Cell depolarization
Phase - 2
A
plateau phase
ca influx balanced by k efflux
17
Q
Cell depolarization
Phase - 3
A
repolarization
continued k efflux
18
Q
Cell depolarization
Phase - 4
A
gradual depolarization
na leak balanced by k efflux
19
Q
ION MOVEMENTS DURING CONTRACTION
1
A
ca entry from outside the cell triggers the release of a much larger quanittiy of ca from the sr
20
Q
ION MOVEMENTS DURING CONTRACTION
2
A
increased ca conc initiates the contractile process
21
Q
ION MOVEMENTS DURING CONTRACTION
3
A
ca is removed by reuptake into the sr and by extrusion fro the cell by a ca/na exhanger
22
Q
ION MOVEMENTS DURING CONTRACTION
4
A
sodium balance is restored by a na/k atapase
23
Q
Bundle of His and Purkinje fibers fast
A
Large Na+current
24
Q
P-wave
A
depolarization of atria
25
PR interval
AV nodal conduction time
26
QRS
depolarization of ventricles, conduction time of ventricles
27
QT interval
ventricular action potential duration
28
T-wave
repolarization of ventricles
29
beta blockers cause heart block
increasing pr interval
30
increasing qt interval causes
torsades
31
Arrhythmias result from
Abnormal impulse generation
Triggered automaticity
Abnormal impulse conduction
Reentry
32
Triggered automaticity
normal depolarization followed by an abnormal depolarization or beat
Early after depolarization –interrupts phase 3
Delayed after depolarization –interrupts phase 4 (from ca overload)
33
Abnormal impulse generation
Disturbance of impulse formation
Interval between depolarizations = duration of action potential + duration of diastolic interval (slope of phase 4)
34
Abnormal impulse conduction
Depressed conduction
Simple block
eg. AV nodal block, bundle branch block (beta blockers can cause this)
35
Reentry
Impulse reenters/excites areas of heart more than once
Must be an obstacle –establishes a circuit
Must be unidirectional block
Conduction time must be long enough that retrograde impulse does not encounter refractory tissues
36
Anti-arrhythmic drugs can
Induce arrhythmias
Depress autonomic properties of abnormal pacemaker cell
Alter conduction characteristics of reentrant loop
37
Anti-arrhythmic drugs
Induce arrhythmias
Must weigh benefits vs. risks
38
Anti-arrhythmic drugs
Depress autonomic properties of abnormal pacemaker cell
Decrease slope of phase 4
Elevate threshold potential
39
Anti-arrhythmic drugs
Alter conduction characteristics of reentrant loop
Facilitate conduction (shorten refractoriness)
Depress conduction (prolong refractoriness)
40
mechanisms that decrease spontaneous firing of pacemaker cell
Decreased phase 4 slope
increased threshold
increased maximum diastolic potential
increased action potential duration
41
Decreased phase 4 slope
beta blockers
42
increased threshold
na and ca chanel blockers
43
increased maximum diastolic potential
adenosine cause hyperpolarization
resting transmembrane is more negative so it takes more time to get to normal
44
increased action potential duration
k chanel blockers
45
k chanel blockers
increase refractory period
46
CLASSIA NA+ CHANNEL BLOCKERS Overview
Disopyramide
Quinidine
Procainamide*
Proarrhythmic(TdP) (can increase QT)
Use-dependence
Open/inactivated channel binding
Block tissues more frequently depolarized (tachycardia)
Intermediate kinetics
47
CLASSIA NA+ CHANNEL BLOCKERS General
slope of phase 0 is less and extend refractory period
48
CLASSIA NA+ CHANNEL BLOCKERS Effects
Decrease Conduction Velocity
increase refractoriness
Decrease Autonomic Properties
49
increase refractoriness is a
K channel blocking effect
50
1a and 1c decrease
heart rate
51
Procainamide effects
Slows upstroke of action potential, slows conduction, prolongs QRS, prolongs action potential duration
Extracardiac: ganglion-blocking
likley due to k blocking affect
52
Procainamide PK
Metabolite N-acetylprocainamide(NAPA) with class III activity
hepaitcally metabolized and renally excreted, short half life
53
Procainamide therapeutic Use
Atrial and ventricular arrhythmias
54
Procainamide ADRs
Excessive APD prolongation, QT prolongation, reversible lupus erythematosus (~33%)
arthritis arthralagia
it is 2nd or third line
55
CLASSIB NA+ CHANNEL BLOCKERS Overview
Lidocaine*
Tocainide
Mexiletine
Not for atrial arrhythmias, just ventricular rhythyms
Activated and inactivated channel binding
Rapid kinetics
56
CLASSIB NA+ CHANNEL BLOCKERS effects
can decrease refractoriness
see effects at faster hr
57
Lidocaine effects
Decreases action potential duration, shortens phase 3 repolarization
58
Lidocaine pk
Extensive first-pass metabolism (3% bioavailable), given IV
Therapeutic levels: 2-6 mcg/mL (helps with infusion rates and side-effects)
decrease ap duration shortens phase 3 repolarization
59
Lidocaine therapeutic use
DOC for termination of VT and prevention of VF after cardioversion in setting of acute ischemia or mi
60
Lidocaine adrs
Least cardiotoxic but associated with neurologic (paresthesias, tremor, nausea, lightheadedness
levels greater than mcg/ml of what was previously stated
61
CLASSIC NA+ CHANNEL BLOCKERS overview
Moricizine
Flecainide (used in afib)
Propafenone
High incidence of drug induced arrhythmias
Cannot be used in structural heart disease (results in increase mortality)
Slow kinetics
62
CLASSIC NA+ CHANNEL BLOCKERS effects
decrease conduction vleocity significantly bc slow on and off, they slow phase 0 depolarization
63
Flecainide overview
Blocks both Na+and K+channels but does not prolong action potential or QT interval
Therapeutic use:
Supraventricular arrhythmia
ADRs:
Severe exacerbation of arrhythmia
64
Propafenone
Similar to flecainide+ β-blocking activity
65
CLASSII Β-BLOCKERS overview
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Propranolol*
Esmolol*
Metoprolol
Decrease automaticity
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Prolong AV conduction
Decrease heart rate and contractility
Decrease O2demand
66
CLASSII Β-BLOCKERS therapeutic use
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Tachyarrhythmias
Atrial flutter
Atrial fibrillation
AV nodal re-entrant tachycardia
Hypertension
Heart failure
Ischemic heart disease
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67
CLASSII Β-BLOCKERS adrs
bradycardia, heart block, potential worsening of reactive airway disease (nonselective), cold extremities, fatigue, cardiac decompensation if heart relying on sympathetic drive (heart failure)
68
Metoprolol pk
b1 selective
Onset of action: 1-2 hours (oral), 20 minutes (IV); t1/2: 3-4 hours
Significant first pass effect: 50%, CYP2D6 metabolism
69
metoprolol toxicity
Similar to other B-blockers but with reduced risk of bronchospasm and diabetes
70
Esmolol
B1-selective, ultra-short-acting
PK:
Onset of action: 2-10 minutes; duration of effect: 10-30 minutes
Metabolized by red blood cell esterases
71
CLASSIII K+ CHANNEL BLOCKERS overview
Amiodarone*
Dofetilide
Sotalol
Diminish outward K+ during repolarization
Increase duration of action potential
Prolong effective refractory period
72
CLASSIII K+ CHANNEL BLOCKERS effects
repolarization no effect of phase 0
73
Amiodarone effects
Prolongs action potential duration (& QT interval), significantly blocks Na+channels, weak adrenergic and calcium channel blockade; broad activity
Extracardiac effects: peripheral vasodilation
74
Amiodarone pk
Bioavailability: 35-65%; hepatic metabolism, major active metabolite
t1/2: 3-10 days (rapid component 50%), several weeks (slower component) (significant for drug interaction, so monitor closely (warfarin metabolism is decreased so you get more bleeding, so decrease warfarin)
Effect maintained 1-3 months after drug discontinued
75
Amiodarone adr
Symptomatic bradycardia, heart block (those with preexisting AV node disease), accumulates in tissues, pulmonary toxicity (& fatal pulmonary fibrosis), abnormal LFTs, skin deposits, gray-blue skin discoloration (bc idodine is depsoited in skin it is part of the structure)
76
Amiodarone ddi
MANY! CYP3A4 blockers (cimetidine) ↑ amiodarone levels; inducers (rifampin) ↓ amiodarone levels; reduce warfarin, statins, digoxin…33-50%
77
CLASSIV CA2+ CHANNEL BLOCKERS
Verapamil
Diltiazem
Decrease inward Ca2+current
Decrease rate of phase 4 spontaneous depolarization
Slows conduction in Ca2+ dependent tissues(AV node)
Use dependent
78
CLASSIV CA2+ CHANNEL BLOCKERS effects
block specific ca channel conformations
slow phase 4 spontaneous depolarization
79
Verapamil effects
Blocks activated and inactivated L-type Ca2+ channels, slows SA node by direct action, suppresses both early and delayed afterdepolarizations
Extracardiac effects: peripheral vasodilation
80
Verapamil pk
Bioavailability: 20% after oral administration
Extensively metabolized in the liver; t1/2: 7 hours
81
Verapamil therapeutic use
SVT, decrease ventricular rate in AFiband AF, angina, HTN
supraventricular tachycardia
psvt
82
Verapamil adr
Hypotension & VF if given to a patient with VT misdiagnosed as SVT; can induce AV block; constipation, lassitude, nervousness, peripheral edema
if you have ventricualr tachycardia
83
OTHER ACLS DRUGS
Adenosine
Atropine
Digoxin
84
Adenosine effects
Nucleoside, activates inward rectifier K+ current and inhibits Ca2+ current resulting in marked hyperpolarization and increased refractory period
85
Adenosine pk
Metabolized in blood and tissue; t1/2: inosine >adenosine monophosphate and hypoxanthine
86
Adenosine therapeutic use
DOC for conversion of paroxysmal SVT
87
Adenosine adrs
Flushing, shortness of breath, chest burning, high grade AV block, atrial fibrillation, headache, hypotension, nausea, paresthesias
make sure you let pt know it will feel like they are having a heart attack while giving
88
Atropine effects
Blocks actions of acetylcholine at parasympathetic sites, increases CO
89
Atropine pk
30-50% excreted unchanged in the urine; t1/2: 2-3 hours
90
Atropine therapeutic use
Bradycardia, neuromuscular blockade reversal, cholinergic poisoning
91
Atropine adrs
Arrhythmia, tachycardia, dizziness, constipation, urinary retention
92
Digoxin effects
Inhibits Na+/K+ATPase, results in positive inotropy, increased intracellular Na+, decreased Ca2+ expulsion, increased free Ca2+. Decreased HR, increased refractory period, decreased conduction velocity
93
Digoxin pk
65-80% absorbed after oral administration
Not extensively metabolized, ~66% excreted unchanged by the kidneys. Must be dose adjusted in renal impairment
t1/2: 36-40 hours
positive inotropic
94
Digoxin therapeutic use
AFib, SVT, heart failure
95
Digoxin adrs
Nausea, vomiting, diarrhea, disorientation, visual disturbances, aberration of color perception, delayed afterdepolarization
yellow green halos in vision
96
Type IA na channel blocker overall effects
Decrease conduction veloxcity
increase refractoriness
decrease autonomic properties
97
Type IB na channel blocker overall effects
No effect on velocity
may decrease refractoriness
dissociate so quickly only effect fast hr
na channel blocker
98
Type IC na channel blocker overall effects
Decrease conduction velocity
no effect on refractoriness
profound decrease in conduction velocity
99
Type II Bblocker overall effects
Decrease conduction velocity
increase refractoriness
decrease autonomic properties
100
type III K channel blocker overall effect
increase refractoriness
increase action potential duration
amiodarone has na beta blocker and ca blocker effects too
keep inside of cell more positive
101
type IV Ca channel blocker overall effects
Decrease conduction velocity
Increase refractoriness
decrease autonomic properties
102
TYPES OF ARRHYTHMIA
Supraventricular arrhythmias: originate above the Bundle of His; characterized by normal QRS complexes
Ventricular arrhythmias: originate below the Bundle of His
Conduction blocks: based on their level or location
103
Supraventricular arrhythmias: originate above the Bundle of His; characterized by normal QRS complexes
Sinus bradycardia
Sinus tachycardia
Paroxysmal supraventricular tachycardia
Atrial flutter
Atrial fibrillation
Wolff-Parkinson-White
Premature atrial contractions
104
Ventricular arrhythmias: originate below the Bundle of His
Premature ventricular contractions
Ventricular tachycardia
Ventricular fibrillation
105
Conduction blocks: based on their level or location
Supraventricular: 1st, 2nd, or 3rddegree AV block
Ventricular: right or left bundle branch block
106
ATRIAL FIBRILLATION overview
Depolarization from ectopic focus or re-entrant circuit impact atria. No single pacemaker in control. “Irregularly irregular
pass through av node randomly
107
ATRIALFIBRILLATION acute treatment
IV CCB, BB, or digoxin
B-blockers (propranolol, metoprolol, esmolol) 1stchoice in high catecholamine states. Should not be used acutely in systolic heart failure.
Non-DHP CCB’s (verapamil, diltiazem) IV produce rapid effects 4-5 min.
Digoxin has much slower onset (max effect 6-8 hours), less effective than BB/CCB in increased sympathetic tone.
108
ATRIAL FIBRILLATION chronic treatment
oral BB, CCB
Digoxin if intolerable side effects to others
109
ATRIAL FIBRILLATION long term strategy
Rate control > rhythm control +/-anticoagulation (CHADS2score)
Rhythm control indications –continued symptoms with adequate rate control, rate not adequately controlled, or intolerable side effects
if converting to normal sinus rhythm you can get ppoing and thrombis int he heart and you get score locck for chads score
110
ATRIAL FIBRILLATION chemical vs electrical cardioversion
Direct current cardioversion most effective
Chemical options: ibutilideIV, propafenonePO, flecainide PO, amiodarone PO/IV, dofetilidePO
111
ATRIAL FIBRILLATION maintenance of nsr
FDA indication –flecainide, dofetilide*, dronedarone
Others –propafenone, amiodarone*
*safe to use in patients with HF
112
PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA(PSVT) overview
AV nodal re-entry
Valsalva maneuver
113
PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA(PSVT) acute treatment
IV adenosine (DOC), verapamil, or diltiazem
Alternative –BB or digoxin if others fail
114
PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA(PSVT) chronic treatment
radiofrequency catheter ablation potentially curative
Drugs –verapamil, diltiazem, BB, or digoxin
115
Verapamil not given in vtac
so adenosine is drug of choice bc it has short half life and does not lead to hemodynamic compromise like verapamil does
116
PREMATURE VENTRICULAR CONTRACTIONS(PVCS)
Ventricular arrhythmias arise from irritable foci within ventricular myocardium
Asymptomatic: do not use class Icagents
CAST trial associated with ↑ mortality
B-blockers within first 24 hours after MI if no contraindications (improves survival)
normally dont treat unless they had mi
117
SUSTAINED VENTRICULAR TACHYCARDIA
Hemodynamic instability: synchronous cardioversion
Stable VT patients: procainamide, sotalol, amiodarone
Implantable cardioverter/defibrillator for
118
Implantable cardioverter/defibrillator for
Survivors of cardiac arrest caused by VF or hemodynamically unstable sustained VT
LVEF ≤ 35%, prior MI at least 40 days after event and NYHA Class II or III
LVEF ≤ 30%, prior MI at least 40 days after event and NYHA Class I
After ICD, prophylactic ablation or adjunctive anti-arrhythmic drugs may be necessary depending on number of discharges
119
TORSADES DE POINTES
Hemodynamic compromise: electrical cardioversion
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Hemodynamically stable: MgSO4
Alternative: class Ibagents
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