IVMS-CV Pharmacology- Antiarrhythmic Agents

CV Pharmacology
Antiarrhythmic Agents
Prepared and presented by:
Marc Imhotep Cray, M.D.
BMS and CK/CS Teacher
Reading:
Antiarrhythmic Drugs
Related Ppt:
Introduction to EKG
Interpretation
Formative Assessment
Practice question set #1
Clinical:
e-Medicine articles
Ventricular Fibrillation
Hypokalemia in
Emergency Medicine

2
Electrophysiology and Cardiac
Arrhythmias
 Cardiac Rhythm
 Normal rate: 60-100 beats per minute
Impulse Propagation: sinoatrial
node atrioventricular (AV node)
His-Purkinje distribution throughout
the ventricle
 Normal AV nodal delay (0.15
seconds) -- sufficient to allow atrial
ejection of blood into the ventricles
See Animated-Interactive Cardiac Cycle
Hyper heart by Knowlege Weavers
Adobe Shockwave Player

3
Electrophysiology and Cardiac
Arrhythmias(2)
 Definition: arrhythmia -- cardiac
depolarization different from previous slide
sequence --
 abnormal origination (not SA nodal)
 abnormal rate/regularity/rhythm
 abnormal conduction characteristics
See: http://www.rnceus.com/ekg/ekgframe.html

4
Cardiac Electrophysiology
 cardiac action potential is a specialized action potential
in heart, with unique properties necessary for function of
electrical conduction system of heart
 cardiac action potential differs significantly in different
portions of heart
 This differentiation of Aps allows different electrical
characteristics of different portions of heart
For instance, specialized conduction tissue of heart
has special property of depolarizing without any external
influence known as cardiac muscle automaticity
See: Interactive animation illustrating the generation of a cardiac action potential

5
Cardiac Electrophysiology(2)
 In cardiac myocytes, release of Ca2+ from
the sarcoplasmic reticulum is induced by
Ca2+ influx into cell through voltage-gated
calcium channels on sarcolemma
 This phenomenon is called calcium-
induced calcium release and increases
myoplasmic free Ca2+ concentration
causing muscle contraction

6
http://www.zuniv.net/physiology/book/chapter11.html

7
 Note that there are important physiological
differences between nodal cells and
ventricular cells;
 the specific differences in ion channels and
mechanisms of polarization give rise to unique
properties of SA node cells,
 most importantly the spontaneous
depolarizations (cardiac muscle automaticity)
necessary for the SA node's pacemaker activity

8
Calcium channels
 Two voltage-dependent calcium channels play critical
roles in the physiology of cardiac muscle:
1. L-type calcium channel ('L' for Long-lasting) and
2. T-type calcium channels ('T' for Transient) voltage-
gated calcium channels
 These channels respond differently to voltage changes
across the membrane:
 L-type channels respond to higher membrane
potentials, open more slowly, and remain open
longer than T-type channels
See Notes Page

9
 resting membrane potential is
caused by difference in ionic
concentrations and conductance
across the membrane of the cell
during phase 4 of action potential
 normal resting membrane potential
in ventricular myocardium is about -
85 to -95 mV
 This potential is determined by
the selective permeability of
the cell membrane to various
ions
 membrane is most permeable
to K+ and relatively
impermeable to other ions
 RMP is therefore dominated by
K+ equilibrium potential
according to the K+ gradient
across the cell membrane
The cardiac action potential has five phases

10
 Maintenance of this
electrical gradient is due
to various ion pumps
and exchange
mechanisms, including
both
Na+-K+ ion exchange
pump and
Na+-Ca2+ exchanger
current
Remember:
Intracellularly K+ is principal cation, and
phosphate and conjugate bases of organic
acids are dominant anions
Extracellularly Na+ and Cl- predominate

11
 Transmembrane
potential - determined
primarily by three ionic
gradients:
 Na+, K+, Ca 2+
 water-soluble, -- not free
to diffuse through the
membrane in response to
concentration or electrical
gradients: depended
upon membrane channels
(proteins)
 Movement through
channels depend on
controlling "molecular
gates"
 Gate-status controlled by:
 Ionic conditions
 Metabolic conditions
 Transmembrane voltage
 Maintenance of ionic
gradients:
 Na+/K+ ATPase pump
 termed "electrogenic" when
net current flows as a result
of transport (e.g., three
Na+ exchange for two K+
ions)

12
Initial permeability state - resting membrane potential
 sodium - relatively impermeable
 potassium - relatively permeable
Cardiac cell permeability and conductance:
 conductance: determined by characteristics of ion
channel protein
 voltage = (actual membrane potential - membrane
potential at which no current would flow, even with
channels open)
 current flow = voltage X conductance

13
Sodium
 Concentration gradient: 140 mmol/L Na+
outside: 10 mmol/L Na+ inside;
 Electrical gradient: 0 mV outside; -90 mV inside
 Driving force -- both electrical and concentration --
tending to move Na+ into the cell
 In the resting state: sodium ion channels are
closed therefore no Na+ flow through the membrane
 In the active state: channels open causing a large
influx of sodium which accounts for phase 0
depolarization

14
Cardiac Cell Phase 0 and Sodium Current
•Note the rapid "upstroke" characteristic
of Phase 0 depolarization.
•This abrupt change in membrane
potential is caused by rapid,
synchronous opening of Na+ channels.
•Note the relationships between the the
ECG tracing and phase 0
Source: http://www.pharmacology2000.com/Cardio/antiarr/antiarrtable.htm

15
Potassium:
 Concentration gradient (140 mmol/L K+ inside; 4
mmol/L K+outside)
 Concentration gradient -- tends to drive potassium out
 Electrical gradient tends to hold K+ in
 Some K+ channels ("inward rectifier") are open in
resting state -- however, little K+ current flows because
of the balance between K+ concentration and
membrane electrical gradients
 Cardiac resting membrane potential: mainly determined
 By extracellular potassium concentration and
 Inward rectifier channel state

16
Spontaneous Depolarization (pacemaker cells)-
phase 4 depolarization
 Spontaneous depolarization occurs because:
 Gradual increase in depolarizing currents (increasing
membrane permeability to sodium or calcium)
 Decrease in repolarizing potassium currents (decreasing
membrane potassium permeability)
 Both
 Ectopic pacemaker: (not normal SA nodal pacemaker)
 Facilitated by hypokalemic states
 Increasing potassium: tends to slow or stop ectopic
pacemaker activity

17
Ca2+: Channel Activation Sequence similar to sodium; but
occurring at more positive membrane potentials (phases 1 and 2)
•Following intense inward Na+
current (phase 0), Ca2+currents:
•Phases 1 & 2, are slowly
inactivated. (Ca2+channel
activation occurred later than
for Na+)

18
Channel Inactivation, Re-establishing Resting Membrane Potential
•Final repolarization (phase 3):
•complete Na+ and Ca2+ channel
inactivation
•Increased potassium permeability
•Membrane potential approaches K+
equilibrium potential -- which
approximates the normal resting
membrane potential

19
 Five Phases:
cardiac action potential in
associated with HIS-purkinje
fibers or ventricular muscle
See Notes page for full explanations

20
Influence of Membrane Resting Potential on
Action Potential Properties:
Factors that reduce the membrane resting
potential & reduce conduction velocity
 Hyperkalemia
 Sodium pump block
 Ischemic cell damage

21
Influence of Membrane Resting Potential
on Action Potential Properties(2)
Factors that may precipitate
or exacerbate arrhythmias
 Ischemia
 Hypoxia
 Acidosis
 Alkalosis
 Abnormal electrolytes
 Excessive catecholamine
levels
 Autonomic nervous
system effects (e.g.,
excess vagal tone)
 Excessive catecholamine
levels
 Autonomic nervous system
effects (e.g., excess vagal
tone)
 Drug effects: e.g.,
antiarrhythmic drugs may
cause arrhythmias)
 Cardiac fiber stretching (as
may occur with ventricular
dilatation in congestive heart
failure)
 Presence of scarred/diseased
tissue which have altered
electrical conduction
properties

22
Intro to Arrhythmias and Drug
Therapy(1)
How do Antiarrhythmic Drugs Work?
Anti-arrhythmic drugs may work by:
 (a) Suppressing initiation site
(automaticity/after-depolarizations) and/or
 (b) Preventing early or delayed
afterdepolarizations and/or
 (c) By disrupting a re-entrant pathway
Ref. Teaching Cardiac Arrhythmias: A Focus on Pathophysiology and Pharmacology

Intro to Arrhythmias and Drug Therapy
(a) Automaticity:
Automaticity may be
diminished by:
 (1) increasing maximum
diastolic membrane
potential
 (2) decreasing slope of
phase 4 depolarization
 (3) increasing action
potential duration
 (4) raising threshold
potential
 All of these factors make it take
longer or make it more difficult
for membrane potential to reach
threshold
 (1) The diastolic membrane
potential may be increased by
adenosine and acetylcholine.
 (2) The slope of phase 4
depolarization may be decreased
by beta receptor blockers
 (3) The duration of the action
potential may be prolonged by
drugs that block cardiac K+
channels
 (4) The membrane threshold
potential may be altered by drugs
that block Na+ or Ca2+ channels.

24
(b) Delayed or Early Afterdepolarizations:
 Delayed or early afterdepolarizations may
be blocked by factors that
 (1) prevent the conditions that lead to
afterdepolarizations
 (2) directly interfere with the inward currents
(Na+, Ca2+) that cause afterdepolarizations

25
(c) Reentry
 For anatomically-determined re-entry such as Wolf-
Parkinson-White syndrome (WPW) drugs arrhythmia
can be resolved by blocking action potential (AP)
propagation
 In WPW-based arrhythmias, blocking conduction
through the AV node may be clinically effective
 Drugs that prolong nodal refractoriness and slow
conduction include: Ca2+ channel blockers, beta-
adrenergic blockers, or digitalis glycosides

26
Intro to Arrhythmias and Drug
Therapy(2)
Atrial fibrillation may result in a high
ventricular following rate
Atrial Fibrillation
 Accordingly, drugs which may reduce ventricular
rate by reducing AV nodal conduction include:
1. calcium channel blockers (verapamil (Isoptin, Calan),
diltiazem (Cardiazem))
2. beta-adrenergic receptor blockers (propranolol
(Inderal)), and
3. digitalis glycosides

27
Arrhythmias and Drug Therapy(3)
calcium channel blockers
Treatment of atrial fibrillation(2)
Verapamil (Isoptin, Calan) &
Diltiazem (Cardiazem)
 Blocks cardiac calcium channels in
slow response tissues, such as the
sinus and AV nodes
 Useful in treating AV reentrant
tachyarrhythmias and in
management of high ventricular
rates secondary to atrial flutter or
fibrillation
 Major adverse effect
(i.v. administration) is
hypotension
 Heart block or sinus
bradycardia can also
occur

28
Arrhythmias and Drug Therapy (4)
beta-adrenergic receptor blockers
Treatment of atrial fibrillation(3): Propranolol
(Inderal)
 Antiarrhythmic effects are due mainly to
beta-adrenergic receptor blockade
 Normally, sympathetic drive results in increased in
Ca2+ ,K+ ,and Cl- currents

29
 Increased sympathetic tone also increases
phase 4 depolarization (heart rate goes
up), and increases DAD (delayed
afterdepolarizations) and EAD (early
afterdepolarization) mediated arrhythmias
 These effects are blocked by beta-adrenergic
receptor blockers

30
 Beta-adrenergic receptor blockers increase
AV conduction time (takes longer) and
increase AV nodal refractoriness, thereby
helping to terminate nodal reentrant
arrhythmias

31
 Beta-adrenergic receptor blockade can also
help reduce ventricular following rates in
atrial flutter and fibrillation, again by acting
at the AV node

32
 Adverse effects of beta blocker therapy
can lead to
1. fatigue,
2. bronchospasm,
3. depression,
4. impotence,
5. attenuation of hypoglycemic symptoms in
diabetic patients
6. worsening of congestive heart failure

33
Class I Antiarrhythmic Drugs
Class I: Sodium Channel Blockers
 Sodium channel blocking antiarrhythmic
drugs are classified as use-dependent in
that they bind to open sodium channels
 Their effectiveness is therefore dependent
upon the frequency of channel opening.

34
Type Ia quinidine
There are three classes or types of
sodium channel blockers:
 Type Ia: prototype:
 quinidine gluconate (Quinaglute,
Quinalan
 Type Ia drugs slow the rate of AP rise
and prolong ventricular effective
refractory period

35
Quinidine
Overview
 dextroisomer of quinine;
quinidine gluconate
(Quinaglute, Quinalan) also
has antimalarial and
antipyretic effects
Pharmacokinetics:
 80%-90%: bound to plasma
albumin
 Rapid oral absorption; rapid
attainment of peak blood
levels (60-90 minutes)
 Elimination half-life: 5-12
hours
 IM injection, possible but
not recommended due to
injection site discomfort
 IV administration: limited
due to myocardial
depression & peripheral
vasodilation

36
Quinidine
Metabolism:
 Hepatic: hydroxylation to inactive metabolites;
followed by renal excretion
 20% excreted unchanged in urine
 Impaired hepatic/renal function:
accumulation of quinidine and metabolites
 Sensitive to enzyme induction by other
agents--
 decreased quinidine blood levels with
phenytoin, phenobarbital, rifampin

37
Quinidine
Mechanism of antiarrhythmic action--
primarily activated sodium channel blockade
which results in:
 Depression of ectopic pacemaker activity
 Depression of conduction velocity
 may convert a one-way conduction blockade to a
two-way (bidirectional) block -- terminating reentry
arrhythmias
 Depression of excitability (particularly in
partially depolarized tissue)
Also see notes page

38
Quinidine
 Effect on the ECG: QT interval lengthening
 Basis: quinidine-mediated reduction in repolarizing
outward potassium current
 Result:
 Longer action potential duration
 Increased effective refractory period
 Reduces reentry frequency; reduced rate
in tachyarrhythmias
 Sodium channel blockade results in
 an increased threshold
 decreased automaticity

39
Quinidine
Uses
 Used to manage nearly
every form of arrhythmia
especially acute and chronic
supraventricular
dysrhythmias
 Ventricular tachycardia (VT)
Frequent indications:
 Prevent recurrence of
supraventricular
tachyarrhythmias (SVT)
 Suppression ventricular
premature contractions
 Approximately 20% of
patients with atrial fibrillation
will convert to normal sinus
rhythm following quinidine
treatment
 Supraventricular
tachyarrhythmia due to Wolff-
Parkinson-White syndrome
(WPW) effective suppression
by quinidine
Also see notes page

40
Quinidine
Side Effects
 Cardiovascular--at (high) plasma concentrations (>
2ug/ml)
 Prolongation (ECG) of PR interval, QRS complex, QT
interval
 Heart block likely with 50% increase in QRS complex
duration (reduced dosage)
 Quinidine syncope: may be caused by delayed
intraventricular conduction, resulting in ventricular
dysrhythmia
 Patients with preexisting QT interval prolongation
or evidence of existing A-V block (ECG): probably
should not be treated with quinidine

41
Quinidine Side Effects (cont.)
 Quinidine is associated with Torsades de pointes, a
ventricular arrhythmias associated with marked QT
prolongation
 Torsades de pointes: Electrophysiological Features
 ventricular origin
 wide QRS complexes with multiple morphologies
 changing R - R intervals
 axis seems to twist about isoelectric line
 This potentially serious arrhythmia occurs in 2% -
8% if patients, even if they have a therapeutic or
subtherapeutic quinidine blood level

42
Other quinidine adverse effects include:
 cinchonism
 blurred vision, decreased hearing acuity,
gastrointestinal upset,headaches and
tinnitus.
 Nausea, vomiting, diarrhea (30% frequency)
 Drug-drug interaction:quinidine gluconate
(Quinaglute, Quinalan)-digoxin (Lanoxin,
Lanoxicaps)
 Quinidine increases digoxin plasma
concentration; may cause digitalis toxicity in
patients taking digoxin or digitoxin

43
Effects on neuromuscular transmission:
 Quinidine gluconate (Quinaglute, Quinalan)
interferes with normal neuromuscular
transmission; enhancing effect of
neuromuscular-blocking drugs
 Recurrence of skeletal muscle paralysis
postoperatively may be associated with
quinidine administration

44
Type Ia Procainamide
Overview:
 Local anesthetic (procaine) analog
 Long-term use avoided because of
lupus-related side effect

45
Procainamide
Metabolism:
 Elimination: renal excretion
& hepatic metabolism;
 procainamide is highly resistant
to hydrolysis by plasma
esterases
 40%-60% excreted unchanged
(renal)
 Renal dysfunction requires
procainamide dosage reduction
 Hepatic metabolism --
acetylation
 cardioactive metabolite:
N-acetylprocainamide
(NAPA);
 NAPA accumulation may
lead to Torsades de
pointes

46
Procainamide
Quinidine and Procainamide similar:
electrophysiological properties
 Possibly somewhat less effective in suppressing
automaticity; possibly more effective in sodium channel
blockade in depolarized cells
 Useful in acute management of supraventricular
and ventricular arrhythmias.
 Drug of second choice for management of sustained
ventricular arrhythmias (in the acute myocardial
infarction setting)
 Effective in suppression of premature ventricular
contractions & paroxysmal ventricular tachycardia
rapidly following IV administration

47
Procainamide
 Most important difference compared
quinidine: procainamide does not
exhibit vagolytic (antimuscarinic)
activity
 Procainamide is less likely to produce
hypotension, unless following rapid IV
infusion
 Ganglionic-Blocking Activity

48
Procainamide Side Effects & Toxicities
 Long term use can be associated with drug-induced,
reversible lupus erythematosus-like syndrome which occurs
at a frequency of 25% to 50%
 Consists of serositis, arthralgia & arthritis
 Occasionally: pleuritis, pericarditis, parenchymal
pulmonary disease
 Rare: renal lupus
 Vasculitis not typically present (unlike systemic lupus
erythematosus)
 Positive antinuclear antibody test is common; symptoms
disappear upon drug discontinuation
 In slow acetylators the procainamide-induced lupus
syndrome occurs more frequently and earlier in therapy
than in rapid acetylators
 Nausea, Vomiting - most common early, noncardiac
complication

49
Class I Antiarrhythmic Drugs Type Ia
Disopyramide (Norpace)
Overview:
 Very similar to quinidine gluconate
(Quinaglute, Quinalan)
 Greater antimuscarinic effects (in
management of atrial flutter & fibrillation, pre-
treatment with a drug that reduces AV
conduction velocity is required)
 Approved use (USA): ventricular arrhythmias

50
Disopyramide (Norpace)
Metabolism:
 Dealkylated metabolite (hepatic); less anticholinergic, less
antiarrhythmic effect compared to parent compound
 50% -- excreted unchanged, renal
 Electrophysiological effects similar to quinidine gluconate
(Quinaglute, Quinalan)
 Similar to quinidine gluconate in effective ventricular and
atrial tachyarrhythmia suppression
Uses:
 prescribed to maintain normal sinus rhythm in patients
prone to atrial fibrillation and flutter
 also used to prevent ventricular fibrillation or tachycardia

51
Disopyramide (Norpace) Side Effects
& Toxicity
 Adverse side-effect profile: different from
qunidine's in that disopyramide (Norpace) is
not an alpha-adrenergic receptor blocker but
is anti-vagal
 Most common side effects: (anticholinergic)
 dry mouth
 urinary hesitancy
 Other side effects: blurred vision, nausea

52
Disopyramide Side Effects &Toxicity
(cont.)
Cardiovascular:
 QT interval prolongation (ECG)
 paradoxical ventricular
tachycardia (quinidine-like)
 Negative inotropism
(significant myocardial
depressive effects)-
undesirable with preexisting
left ventricular dysfunction
 (may promote congestive
heart failure, even in
patients with no prior
evidence of myocardial
dysfunction)
 Disopyramide is not a
first-line antiarrhythmic
agent because of its
negative inotropic effects
 If used, great caution
must be exercised in
patients with congestive
heart failure
 Can cause torsades de
pointes, a ventricular
arrhythmia

53
Type Ib
 Class Ib agents are often effective in
treating ventricular arrhythmias
Example:lidocaine
 Type Ib agents exhibit rapid
association and dissociation from the
channel

54
Class I Antiarrhythmic Drugs Type Ib
(Class IB, Sodium Channel Blocker)
Mexiletine (Mexitil)
 Overview
 Amine analog of lidocaine (Xylocaine), but
with reduced first-pass metabolism
 Suitable for oral administration
 Similar electrophysiologically to lidocaine

55
Type Ib Mexiletine
Clinical Use:
 Chronic suppression of ventricular
tachyarrhythmias
 Combination with a beta adrenergic receptor
blocker or another antiarrhythmic drug (e.g.
quinidine gluconate (Quinaglute, Quinalan) or
procainamide (Procan SR, Pronestyl-SR)):
synergistic effects allow:
 reduced mexiletine dosage
 decreased side effect incidence

56
Type Ib Mexiletine (Cont.)
 Possibly effective:
decreasing neuropathic
pain when alternative
medications have proven
ineffective-- applications
(on-label use):
 diabetic neuropathy
 nerve injury
Side effects:
 Epigastric burning:
usually relieved by a
taking drug with food
 nausea (common)
 Neurologic side effects:
 diplopia, vertigo,
slurred speech
(occasionally), tremor

57
Class I Antiarrhythmic Drugs Type Ib
(Class IB, Sodium Channel Blocker)
Lidocaine (Xylocaine)
Overview and
Pharmacokinetics:
 Local anesthetic administered
by i.v. for therapy of
ventricular arrhythmias
 Extensive first-pass effect
requires IV administration
 Half-life: two hours
 Infusion rate: should be
adjusted based on lidocaine
plasma levels
Metabolism
 Hepatic;some active
metabolites

58
Lidocaine (Xylocaine) (Class Ib,
Sodium Channel Blocker)
Factors influencing loading and maintenance
doses:
 Congestive heart failure (decreasing volume of
distribution and total body clearance)
 Liver disease: plasma clearance -- reduced;
volume of distribution -- increased; elimination
half-life substantially increased (3 X or more)
 Drugs that decrease liver blood flow (e.g.
cimetadine, propranolol), decreased lidocaine
clearance (increased possible toxicity)
Pharmacokinetics cont. :

59
Lidocaine (Xylocaine) (Class Ib,
Sodium Channel Blocker) (Cont.)
Cardiovascular Effects:
 Site of Action: Sodium Channels
 Blocks activated and inactivated sodium
channels (quinidine blocks sodium channels
only in the activated state)
 No significant effect on QRS or QT interval or
on AV conduction (normal doses)
 Lidocaine (Xylocaine) decreases automaticity
by reducing the phase 4 slope and by
increasing threshold
Pharmacodynamics:

60
Lidocaine (Xylocaine) (Cont.)
 lidocaine is more effective in suppressing activity
in depolarized, arrhythmogenic cardiac tissue but
little effect on normal cardiac tissue -basis for this
drug's selectivity
 Very effective antiarrhythmic agent for arrhythmia
suppression associated with depolarization (e.g.,
digitalis toxicity or ischemia)
 Comparatively ineffective in treating arrhythmias
occurring in normally polarized issue (e.g., atrial
fibrillation or atrial flutter)

61
Clinical Uses:
 Suppression of ventricular arrhythmias (limited
effect on supraventricular tachyarrhythmias)
 May reduce incidence of ventricular
fibrillation during initial time frame
following acute myocardial infarction
 Suppression of reentry-type rhythm disorders:
 premature ventricular contractions (PVCs)
 ventricular tachycardia

62
Side Effect/Toxicities
 Overdosage:
 vasodilation
 direct cardiac
depression
 decreased cardiac
conduction -
bradycardia;
prolonged PR
interval; widening
QRS on ECG
 Major side effect -
neurological
 Large doses, rapidly
administered can result in
seizure
 Factors that reduce
seizure threshold for
lidocaine:
 hypoxemia,
hyperkalemia,
acidosis
 Otherwise: CNS
depression, apnea

63
Tocainide (Class I, Sodium Channel
Blocker)
Tocainide
 Amine analog of lidocaine, similar to mexiletine,
orally active --but with reduced first-pass
metabolism
 Used for chronic suppression of ventricular
tachyarrhythmias refractory to less toxic
agents
 Electrophysiologically similar to lidocaine
 Similar to mexiletine: tocainide + beta-adrenergic
receptor blocker or another antiarrhythmic drug:
synergism
 e.g.-Combination with quinidine may increase
efficacy and diminish adverse effects

64
Tocainide (Class I, Sodium Channel
Blocker) (cont.)
Side Effects:
 Profile similar to mexiletine
 suitable for oral administration, but RARELY
USED due to possibly fatal bone marrow
aplasia and pulmonary fibrosis
 tremor and nausea are major dose-related
adverse side effects
 Excreted by kidney, accordingly dose should be
reduced in patients with renal disease

65
Cardiac Electrophysiology online
animations and interactive tutorials
 Electro Cardio Gram by Knowlege Weavers
 Interpreting an EKG
 EKG Tutorial RnCeus Interactive
 Electrocardiogram -ECG Technician Nobel eMuseum
 Hyper heart by Knowlege Weavers
 The Arrhythma Center HeartCenterOnline

66
Reference Resource (Textbooks)
Principles of Pharmacology: The Pathophysiologic Basis of Drug
Therapy Cairo CW, Simon JB, Golan DE. (Eds.); LLW 2012 (Google
Books Online).
Goodman and Gilman’s The Pharmacological Basis of Therapeutics.
Brunton LL, Chabner BA , Knollmann BC (Eds.); M-H 12th ed. 2011.
Basic and Clinical Pharmacology, Katzung, Masters, Trevor; M-H 12th
ed.

IVMS-CV Pharmacology- Antiarrhythmic Agents

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Destaque

Destaque (20)

Semelhante a IVMS-CV Pharmacology- Antiarrhythmic Agents

Semelhante a IVMS-CV Pharmacology- Antiarrhythmic Agents (20)

Mais de Imhotep Virtual Medical School

Mais de Imhotep Virtual Medical School (20)

Último

Último (20)

IVMS-CV Pharmacology- Antiarrhythmic Agents