Individualized Webcam facilitated and e-Classroom USMLE Step 1 Tutorials with Dr. Cray. 1 BMS Unit is 4 hr. General Principles and some Organ System require multiple units to complete in preparation for the USMLE Step 1 A HIGH YIELD FOCUS IN Biochemistry / Cell Biology, Microbiology / Immunology and the 4 P’s-Phiso, Pathophys, Path and Pharm. Webcam Facilitated USMLE Step 2 Clinical Knowledge and Clinical Skills diadactic tutorials /1 Unit is 4 hours, individualized one-on-one and group sessions, Including all Internal Medicine sub-sub-specitialities. For questions or more information.. drcray@imhotepvirtualmedsch.com
This presentation about cell wall inhibitors specially beta lactam antibiotics ..... that help you to understand how B-lactam antibiotics work on bacteria......
This presentation about cell wall inhibitors specially beta lactam antibiotics ..... that help you to understand how B-lactam antibiotics work on bacteria......
Since I couldn't find a good enough book on arrhythmia which included everything, I decided to make one. In the hope that it helps someone, since collecting notes is time-consuming (I've been there), I'm posting this in here.
I collected data from various books of Electrocardiography and arrhythmia, various sites, a few research studies and some people's public notes.
I think I included all types of arrhythmia and heart blocks, let me know what do you think of it or in case I left something out.
Anatomy and physiology of the cardiac system
The electrocardiogram a, curves and interpretation of the first and second heart sounds. Generation of action potential within the myocardium ,the gap junctions and how they propagate electrical pilese from sinoatrial mode and ectopoic heartbeat.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
How to Build a Module in Odoo 17 Using the Scaffold Method
IVMS-CV Pharmacology- Antiarrhythmic Agents
1. 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. 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. 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. 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. 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
7. 7
Cardiac Electrophysiology(4)
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. 8
Cardiac Electrophysiology(5)
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. 9
Cardiac Electrophysiology(6)
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. 10
Cardiac Electrophysiology(7)
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. 11
Cardiac Electrophysiology(8)
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. 12
Cardiac Electrophysiology(9)
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. 13
Cardiac Electrophysiology(10)
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. 14
Cardiac Electrophysiology(11)
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. 15
Cardiac Electrophysiology(12)
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. 16
Cardiac Electrophysiology(13)
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. 17
Cardiac Electrophysiology(14)
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+)
Source: http://www.pharmacology2000.com/Cardio/antiarr/antiarrtable.htm
18. 18
Cardiac Electrophysiology(15)
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
Source: http://www.pharmacology2000.com/Cardio/antiarr/antiarrtable.htm
19. 19
Cardiac Electrophysiology(16)
Five Phases:
cardiac action potential in
associated with HIS-purkinje
fibers or ventricular muscle
See Notes page for full explanations
20. 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. 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. 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
23. Intro to Arrhythmias and Drug Therapy
How do Antiarrhythmic Drugs Work?
(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. 24
Intro to Arrhythmias and Drug Therapy
How do Antiarrhythmic Drugs Work?
(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. 25
Intro to Arrhythmias and Drug Therapy
How do Antiarrhythmic Drugs Work?
(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. 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. 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. 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. 29
Arrhythmias and Drug Therapy (5)
beta-adrenergic receptor blockers
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. 30
Arrhythmias and Drug Therapy (6)
beta-adrenergic receptor blockers
Beta-adrenergic receptor blockers increase
AV conduction time (takes longer) and
increase AV nodal refractoriness, thereby
helping to terminate nodal reentrant
arrhythmias
31. 31
Arrhythmias and Drug Therapy (7)
beta-adrenergic receptor blockers
Beta-adrenergic receptor blockade can also
help reduce ventricular following rates in
atrial flutter and fibrillation, again by acting
at the AV node
32. 32
Arrhythmias and Drug Therapy (8)
beta-adrenergic receptor blockers
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. 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. 34
Class I Antiarrhythmic Drugs
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. 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. 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. 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. 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. 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. 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. 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. 42
Quinidine Side Effects (cont.)
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. 43
Quinidine Side Effects (cont.)
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. 44
Class I Antiarrhythmic Drugs
Type Ia Procainamide
Overview:
Local anesthetic (procaine) analog
Long-term use avoided because of
lupus-related side effect
45. 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. 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. 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. 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. 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. 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. 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. 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. 53
Class I Antiarrhythmic Drugs
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. 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. 55
Class I Antiarrhythmic Drugs
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. 56
Class I Antiarrhythmic Drugs
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. 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. 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. 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. 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. 61
Lidocaine (Xylocaine) (Cont.)
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. 62
Lidocaine (Xylocaine) (Cont.)
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. 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. 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. 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. 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.