Antiarrhythmic drugs are classified according to their mechanism of action and effects on cardiac electrophysiology. Class I drugs block sodium channels, while Class II are beta blockers, Class III block potassium channels, and Class IV block calcium channels. The main classes used are Class Ia (quinidine, procainamide), Class Ic (flecainide, propafenone), Class III (amiodarone, sotalol), and calcium channel blockers (verapamil, diltiazem). Each drug has therapeutic uses for specific arrhythmias as well as adverse effects that must be considered.
ANTI-ARRYTHMIC DRUGS
INTRODUCTION:
A Heart arrhythmia is an irregular heartbeat.
Arrhythmias occur when the electrical signals that coordinate the heart's beats don't work properly.
Scope: This subject is intended to impart the fundamental knowledge on various aspects
(classification, mechanism of action, therapeutic effects, clinical uses, side effects and
contraindications) of drugs acting on different systems of body and in addition,emphasis
on the basic concepts of bioassay. Objectives: Upon completion of this course the student should be able to
1. Understand the mechanism of drug action and its relevance in the treatment of
different diseases
2. Demonstrate isolation of different organs/tissues from the laboratory animals by
simulated experiments
3. Demonstrate the various receptor actions using isolated tissue preparation
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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2. Learning Outcomes….
• Describe the cardiac electrophysiology
• Describe the causes of arrhythmia
• Classify antiarrhythmics
• Describe the mechanism of action, therapeutic uses,
pharmacokinetics and adverse effects of each class of antiarrhythmic
drugs
3. Antiarrhythmics
• These are drugs used to prevent or treat irregularities of cardiac
rhythm.
• Arrhythmias are the most important cause of sudden cardiac death
Ischaemia, electrolyte and pH imbalance, mechanical injury, stretching
(due to heart failure), neurogenic and drug influences, including
antiarrhythmic drugs themselves, can cause arrhythmias by altering
electrophysiological properties of cardiac fibres.
4.
5. Cardiac
electrophysiology
Heart contains specialized
cells that exhibit
automaticity
Pacemaker cells differ from
other myocardial cells –
spontaneous
depolarization during
diastole (phase 4) by
inward positive Na current
Spontaneous
depolarization is fastest in
SA node
6. Arrhythmias
• Arrhythmias are caused by abnormalities in:
• Impulse formation
• Conduction in the myocardium
• Arrhythmias are classified according to the anatomic site of the
abnormality…….atria, AV node or ventricles
Common arrhythmias requiring drug therapy:
Atrial arrhythmias – atrial flutter, atrial fibrillation
Supraventricular tachycardias – AV nodal re-entry, Acute supraventricular tachycardia
Ventricular tachycardias – Acute ventricular tachycardia, ventricular fibrillation
7. Abnormal automaticity
• Normally, SA node sets the pace of contraction of myocardium
• If cardiac sites other than SA node show enhanced automaticity,
arrhythmias arise
Most antiarrhythmic drugs suppress automaticity by blocking either Na or Ca channels
This decreases the slope of phase 4 depolarization
Raises the threshold of discharge to a less negative voltage
Leading to overall decrease in frequency of discharge
This effect is more pronounced in ectopic pacemaker activity than in normal cells
8. Abnormalities in
impulse conduction
A phenomenon called re-entry can occur if a
unidirectional block caused by myocardial injury or a
prolonged refractory period results in abnormal
conduction pathway
Antiarrhythmic agents prevent re-entry by slowing
conduction and/or increasing the refractory period –
thus creating a unidirectional block into a bidirectional
block
9. Antiarrhythmic drugs
Antiarrhythmic drugs are used to:
Decrease or increase conduction velocity
Alter the excitability of cardiac cells by changing the duration of the
effective refractory period
Suppress abnormal automaticity
• They are classified according to the Vaughan-Williams Classification
according to their predominant effects on the action potential
Antiarrhythmics have
narrow therapeutic
window – have
dangerous
proarrhythmic actions
Limitations of Vaughan-Williams Classification:
Antiarrhythmic drugs have multiple electrophysiological and pharmacological effects
Action depends on route of administration, plasma levels and active metabolites (metabolites may have a different action)
10. Antiarrhythmic drugs
• Class I (Na channel blockers)
IA: Quinidine, Procainamide, Disopyramide
IB: Lidocaine, Mexiletine
IC: Flecainide, Propafenone
• Class II (β blockers)
Atenolol
Metoprolol
Esmolol
• Class III (K channel blockers)
Sotalol Dofetilide
Amiodarone Ibutilide
• Class IV (Ca channel blockers)
Diltiazem
Verapamil
• Other antiarrhythmics
Adenosine
Digoxin
Magnesium sulphate
Ranolazine
11. Class I Antiarrhythmic drugs
• Block voltage-sensitive Na channels
• Subdivided into three groups according to the effect on the duration
of the cardiac action potential:
• IA – intermediate blockers of Na channels
• IB – fast blockers of Na channels
• IC – slow blockers of Na channels
The use of Na channels has declined due to their pro-arrhythmic effects, particularly in
patients with reduced left ventricular function and atherosclerotic heart disease
12. Class IA antiarrhythmic drugs
Mechanism of action:
• Bind to open and inactivated Na channels and prevent Na influx
Slows the rapid upstroke during phase 0
• Decrease the slope of
phase 4 spontaneous depolarization
• Inhibit K channels
• Block Ca channels
Quinidine (prototype)
Procainamide
Disopyramide
Slows conduction
velocity and increases
refractoriness
14. Class IA antiarrhythmic drugs
Additional properties:
• Quinidine also has mild :
α-adrenergic blocking property (not seen in procainamide and
disopyramide)
Anticholinergic property (procainamide has less anticholinergic
activity while disopyramide has more anticholinergic activity)
• Disopyramide has greater negative inotropic effect and causes
peripheral vasoconstriction
Quinidine (prototype)
Procainamide
Disopyramide
15. Class IA antiarrhythmic drugs
Quinidine:
Atrial, AV junctional and
ventricular tachyarrythmias
Rarely used due to its adverse
effects
Procainamide:
Used as intravenous formulation
to treat acute atrial and
ventricular arrhythmias
Mostly replaced by electrical
cardioversion and amiodarone
Quinidine (prototype)
Procainamide
Disopyramide
Therapeutic Uses:
Disopyramide:
Vagally mediated atrial fibrillation, Hypertrophic obstructive cardiomyopathy
and as an alternative therapy in ventricular arrhythmias
16. Class IA antiarrhythmic drugs
Pharmacokinetics:
Quinidine (prototype)
Procainamide
Disopyramide
Quinidine
• Gluconate or sulfate
salt is well absorbed
orally
• Undergoes hepatic
metabolism by
CYP3A4 forming
active metabolites
Procainamide
• Given iv
• Acetylated in the liver to
N-acetylpocainamide
(NAPA)….NAPA has
properties and adverse
effects of class III drug
• Dose needs to be reduced
in renal
dysfunction…(NAPA is
excreted through kidneys)
Disopyramide
• Well absorbed after
oral administration
• Metabolized by
CYP3A4 to inactive
metabolites
• Half of drug is
excreted unchanged
by kidneys
17. Class IA antiarrhythmic drugs
Adverse effects:
• Should not be used in patients of atherosclerotic heart disease or systolic
heart failure (due to enhanced pro-arrhythmic properties and ability to
worsen heart failure)
• Cinchonism – Quinidine
(blurred vision, tinnitus, headache, disorientation and psychosis)
• Hypotension and DLE - Procainamide
• Anticholinergic side effects – Disopyramide
(dry mouth, urinary retention, blurred vision and constipation)
• Drug interactions are common (quinidine inhibits CYP2D6 and P-gp;
Disopyramide and quinidine should be used cautiously with CYP3A4
inhibitors)
Quinidine (prototype)
Procainamide
Disopyramide
18. Class IB antiarrhythmic drugs
• Class IB agents rapidly associate and dissociate with Na channels
Mechanism of action:
• Block Na channel
• Shorten phase 3 repolarization
• Decrease the duration of action potential
Uses:
• Intravenous lidocaine is used as an alternative (to amiodarone) in treating
ventricular arrhythmias (VT and VF)
• Iv lidocaine is combined with amiodarone for VT storm
• Oral mexiletine is used for chronic treatment of ventricular arrhythmias
(with amiodarone)
Lidocaine
Mexiletine
No negative inotropic effect
20. Class IB antiarrhythmic drugs
Pharmacokinetics:
• Lidocaine:
Given iv because of extensive
first pass metabolism
Metabolized to active
metabolites by CYP1A2 and
CYP3A4
• Mexiletine :
Well absorbed orally
Metabolized in the liver by
CYP2D6 to inactive metabolites
and excreted via biliary route
Lidocaine
Mexiletine
Adverse effects:
Lidocaine: (wide therapeutic index) - Nystagmus (early indicator of toxicity), drowsiness, slurred
speech, paresthesia, agitation, confusion, convulsions
……..limits the duration of continuous infusion
Mexiletine: (narrow therapeutic index) - Nausea, vomiting, dyspepsia
21. Class IC antiarrhythmic drugs
• Slowly dissociate from resting Na channels and show prominent
effects even at normal heart rates.
• Avoided in structural heart disease such as left ventricular
hypertrophy, heart failure and atherosclerotic heart disease because
of negative inotropic effects and pro-arrhythmic effects
Flecainide
Propafenone
22. Class IC antiarrhythmic drugs
Mechanism of action:
Suppress phase 0 upstroke in Purkinje and myocardial fibres
Leads to marked slowing of conduction in all cardiac tissues
• Minor effect on duration of AP and refractoriness
• Increase in threshold potential reduces automaticity
Flecainide also blocks K channels (leads to increased duration of AP)
Propafenone has weak β- blocking property (no effect on K channels)
Flecainide
Propafenone
24. Class IC antiarrhythmic drugs
Therapeutic uses:
• Used to maintain sinus rhythm in AF (in patients without structural
heart disease)
• Used in combination with an AV blocking agent to prevent conduction
through AV node in cases of atrial flutter/fibrillation
(class IC agents increase AV nodal conduction)
• Treatment of refractory ventricular arrhythmias
Flecainide
Propafenone
25. Class IC antiarrhythmic drugs
Adverse effects:
Blurred vision, dizziness, nausea
Propafenone can also cause bronchospasm (avoided in asthmatics)
Propafenone is an inhibitor of P-gp
Both drugs should be used cautiously with potent inhibitors of CYP2D6
Flecainide
Propafenone
Both drugs are metabolized by CYP2D6
Propafenone is also metabolized by CYP1A2 and CYP3A4
Metabolites are excreted in urine and faeces
26. Class II antiarrhythmic agents
• Class II agents are β-blockers
• They diminish phase 4 depolarization
• Depress automaticity, prolong AV conduction, and decrease heart rate
and contractility
Uses:
Used in treating arrythmias caused by increased sympathetic activity
Atrial flutter
Atrial fibrillation
AV nodal re-entrant tachycardia
β-blockers prevent life-threatening ventricular arrythmias following
myocardial infarction
Propranolol
Atenolol
Metoprolol
Esmolol
27. Class II antiarrhythmic agents
Propranolol:
• Useful in treating inappropriate
sinus tachycardia.
• Atrial and nodal ESs, especially
those provoked by emotion or
exercise
• Highly effective in sympathetically
mediated arrhythmias seen in
pheochromocytoma and during
anesthesia
Metoprolol:
Compared to nonselective beta
blocker, it reduces the risk of
bronchospasm
Esmolol:
Very short and fast acting beta
blocker
Used iv to control arrythmias
during surgery
Metabolized by esterases in
RBCs….no pharmacokinetic drug
interactions
Common adverse effects:
bradycardia,
hypotension, and fatigue
28. Class III antiarrhythmic drugs
Block K channels
Diminish the outward K current during repolarization
Prolong the duration of action potential, thus prolong the effective
refractory period
(without altering phase 0 of depolarization or the resting membrane
potential)
Amiodarone
Dronedarone
Sotalol
Dofetilide
Ibutilide
All Phase III drugs have the potential to induce arrhythmias
30. Class III antiarrhythmic drugs
Amiodarone:
• Contains iodine (structurally related to thyroxine)
• Shows Class I, II, III and IV actions in addition to α blocking activity
• Prolongs the action potential duration and the refractory period by
blocking K channels
Uses:
• Atrial fibrillation/flutter
• Severe supraventricular tachyarrhythmia
• Ventricular tachyarrhythmias
Least pro-arrhythmic
agent among class I and
III drugs
31. Class III antiarrhythmic drugs
Amiodarone:
• Incompletely absorbed after oral administration
• Long t ½ of several weeks
• Distributes extensively in tissues
• Loading doses are needed to achieve full clinical effects
• Numerous drug interactions (it is metabolized by CYP3A4; inhibitor of P-gp,
CYP1A2, CYP2C9, CYP2D6
Adverse
Effects
Pulmonary
fibrosis
Neuropathy Hepatotoxicity Corneal deposits
Blue-gray discolouration of skin Hypo/hyper-
thyroidism
Optic neuritis
32. Class III antiarrhythmic drugs
Dronedarone:
• Less lipophilic and has shorter t ½
• No iodine component and no thyroid
dysfunction
• Has class I, II, III and IV actions
• Can cause liver failure
• Contraindicated in heart failure and
permanent AF
• Used to maintain sinus rhythm in
atrial fibrillation/flutter
Sotalol:
• Class III antiarrhythmic agent with
non-selective β blocking activity
• Blocks rapid outward K current
(delayed rectifier current)
• Prolongs both repolarization and
duration of action potential, thus
lengthening the refractory period
• Used to maintain sinus rhythm in
AF/flutter or refractory PSVT
33. Class III antiarrhythmic drugs
Dofetilide:
• Pure K channel blocker
• First line anti-arrhythmic drug in
persistent Atrial fibrillation (in HF or
CAD)
• Excreted through kidneys: so drugs
that inhibit active tubular secretion
are contraindicated with dofetilide
Ibutilide:
• K channel blocker that also activates
inward Na current (class III and IA
action)
• Drug of choice for chemical
conversion of atrial flutter (electric
cardioversion is preferred)
34. Class IV antiarrhythmic drugs
• Non-dihydropyridne Ca channel blockers (verapamil and diltiazem) are
used
Bind to open depolarized voltage-sensitive Ca channels
Decrease the inward Ca current
• These drugs are use-dependent: prevent repolarization until the drug
dissociates from the channel
• Decrease rate of phase 4 spontaneous depolarization
• Slow conduction in tissues that are dependent on Ca currents (AV node, SA
node)
35. Class IV antiarrhythmic drugs
Uses:
• More effective in atrial tachyarrhythmias than ventricular tachycardia
• Useful in treating re-entrant supraventricular tachycardia
• Reduce the ventricular rate in atrial flutter/fibrillation
Adverse effects:
• Bradycardia, hypotension, peripheral edema
36. Digoxin
• Inhibits Na-K-ATPase
• Shortens the refractory period in atrial and ventricular cells
• Prolongs the effective refractory period and diminishes the
conduction velocity in AV node
• Used to control ventricular response rate in atrial fibrillation and
flutter
• At toxic doses it can cause ectopic ventricular betas that may result in
VT and fibrillation
37. Adenosine
• Adenosine:
Decreases the conduction velocity
Prolongs the refractory period
Decreases automaticity in the AV node
• It has extremely short duration of action (10-15 seconds) due to uptake
by erythrocytes and endothelial cells
Adenosine (iv) is used for converting acute supraventricular tachycardias
Can cause flushing, chest pain and hypotension
38. Magnesium sulphate
• Magnesium is necessary for transport of Na, Ca, and K across cell
membranes
• It slows the rate of SA node firing and prolongs conduction time
Magnesium sulphate (iv) is used for:
Torsades de pointes
Digoxin-induced arrhythmia
39. Ranolazine
• Antianginal drug with antiarrhythmic properties (similar to
amiodarone)
• Shortens repolarization and action potential duration ( similar to
mexiletine)
• Used to treat refractory atrial and ventricular arrhythmias
• Dizziness and constipation are common adverse effects
40. Antiarrhythmic drugs used to treat different
arrythmias
CONDITION DRUG CLASS DRUG OF CHOICE COMMENTS
Sinus tachycardia Class II, IV Propranolol Other underlying causes
may need treatment
Atrial fibrillation/flutter Classes IA, IC, II, III, IV
Digitalis, adenosine
Esmolol, verapamil,
digoxin
Ventricular rate control is
important;
anticoagulation needed
Paroxysmal
supraventricular
tachycardia
Classes IA, IC, II, III, IV,
adenosine
Adenosine, esmolol -
AV block Atropine Atropine Acute reversal
Ventricular tachycardia Classes I,II,III Lidocaine, procainamide,
amiodarone
-
Ventricular fibrillation Classes II, IV, Mg salts Lidocaine, amiodarone -
Digitalis toxicity Class IB, Mg salts; KCl - -
42. References
• Lippincott Illustrated Reviews: Pharmacology(6th ed.). Philadelphia,
PA: Wolters Kluwer.
• Clinical Medicine: A Textbook for Medical Students & Kumar PJ
and Clark ML (8th ed.); Elsevier Saunders
Editor's Notes
Phases of the Cardiac Action Potential
Phase 0 is the phase of a stable resting action potential, when the cells are polarized and in an excitable state awaiting a stimulus, which will cause rapid depolarization. When a stimulus above the threshold potential strikes the cell the cell begins to depolarize. Sodium ions rush into the cell causing the electrochemical gradient between the inside and outside of the cell to rapidly move towards zero.
Phase 1 is known as the depolarization phase in which the electrochemical voltage change is so rapid that the voltage overshoots the zero potential and stops out around +20mV. Phase 1 is a very short phase where the potential difference comes to rest near 0mV. During phase 2 of the cardiac action potential the fast sodium channels close and the influx of sodium ceases completely. While this is happening, the potassium ions continue to be depleted from the cell resulting in a small decrease in positively charged ions within the cardiac cell membrane.
Phase 2 of the cardiac action potential is known as the plateau phase where the cell membrane action potential is maintained near 0mV by the infusion of calcium ions. Calcium enters the myocardial cells, causing a large secondary release of calcium and causing contraction of the myocardium. The cell is in a prolonged depolarized state and restoration of the resting membrane potential is beginning to take place.
Phase 3 is known as the rapid repolarization phase. This phase is initiated by the closing of the slow calcium channels, which leads to an increase in cellular permeability and efflux of potassium. Repolarization is completed by the end of this phase of the cardiac action potential, and the cell is restored to its repolarized state of -90mV.
Phase 4 identifies the period between action potentials and the cell is repolarized and ready to fire again. During this phase the cell is negatively charged compared with the extracellular areas. There is an excess of sodium ions within the cell and potassium ions outside of the cell. The sodium and potassium pump is commenced and sodium is slowly pumped outside of the cell, while potassium enters the cell, raising the resting potential of the membrane so that the entire process can occur again
Class I drug – slow conduction
Class III drugs – increase the refractory period
These drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use dependence (or state dependence), and it enables drugs to block cells that are discharging at an abnormally high frequency, without interfering with the normal beating of the heart
They have concomitant class III action ( they can precipitate arrhythmia that can progress to ventricular fibrillation
Class IB drugs are useful in treating ventricular arrhythmias
Amiodarone is the drug of choice for ventricular fibrillation and ventricular tachycardia
Mexiletine has a narrow therapeutic index and caution should be used when administering the drug with inhibitors of CYP2D6
Automaticity is reduced by an increase in the threshold potential, rather than a decrease in the slope of phase 4 depolarization.
Flecainide also blocks K channels, lading to increased duration of the action potential.
Propafenone, like flecainide, slows conduction in all cardiac tissues but does not block K channels.
Due to their negative inotropic effect, they are avoided in patients with structural heart disease
Contraindicated in severe CAD as it increases the risk of proarrhythmias and sudden cardiac death…..they should be used in combination with an AV blocking agent in order to prevent rapid AF conduction through the AV node resulting in very fast ventricular rates if a breakthrough episode occurs since class IC drugs also act to increase AV nodal conduction
Metoprolol is the most widely used beta blocker for the treatment of cardiac arrhythmias…..compared to non-selective beta blockers (ropranolol)…it reduces the risk of bronchospasm. It is extensively metabolized by CYP2D6 and has CNS penetration (less than propranolol but more than atenolol)
The dominant effect of amiodarone is prolongation of the action potential duration and refractory period by blocking the K channels
Full clinical effects may not be achieved until months after initiation of therapy unless loading doses are employed
Use of low doses and close monitoring reduces toxicity, while retaining clinical efficacy
L-sotalol has beta blocker activity and D-sotalol has class III antiarrhythmic activity