This document discusses various drugs used to treat cardiac arrhythmias. It describes the mechanisms of action, therapeutic uses, pharmacokinetics, and adverse effects of antiarrhythmic drugs including quinidine, procainamide, disopyramide, lidocaine, mexiletine, tocainide, flecainide, propafenone, beta blockers like propranolol and metoprolol, amiodarone, sotalol, and dofetilide. The drugs have different effects on cardiac conduction and automaticity and are used to treat various atrial and ventricular arrhythmias.
This presentation deals with the use of various drugs in the treatment of heart failure such as Digoxin, ace inhibitors, beta bloockers, calcium channel blockers
Vasodilators and antihypertensive agents-Dr.Jibachha Sah,M.V.Sc,LecturerDr. Jibachha Sah
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
This presentation deals with the use of various drugs in the treatment of heart failure such as Digoxin, ace inhibitors, beta bloockers, calcium channel blockers
Vasodilators and antihypertensive agents-Dr.Jibachha Sah,M.V.Sc,LecturerDr. Jibachha Sah
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell.Caused by unequal distribution of ions inside vs. outside cell ,Na+ higher outside than inside cell,Ca+ much higher “ “ “ “
K+ higher inside cell than outside Maintenance by ion selective channels, active pumps and exchangers
Definition of arrhythmia - background on cardiac physiology including conduction in heart - action potential - pathogensis of arrhythmia - causes and risk factors for arrhythmia- diagnosis of arrhythmia - symptoms of tachyarrhythmias and bradyarrhythmias - investigations for arrhythmia - treatment of arrhythmia - pharmacological and other modalities of therapy for arrhythmia - managment of different types of arrhythmias
Introduction
Generic Name: Atorvastatin
Brand Names: Lipitor,Atorvast,Divastin,Lipicut
Atorvastatin a group of drugs called HMG CoA reductase inhibitors, or "statins."
Atorvastatin reduces levels of "bad" cholesterol or LDL and triglycerides in the blood, and also increasing levels of "good" cholesterol or HDL.
4Mechanism of action
Statin drugs competitively inhibit HMG-CoA, which is an enzyme that catalyzes the synthesis of HMG-CoA in to cholesterol. Therefore, it effectively the synthesis of new cholesterol. It leads to an increase in LDL receptor on Liver cells to take in more LDL, effectively decreasing LDL in the body
5Pharmacokinetics
Absorption
Atorvastatin undergoes rapid absorption when taken orally, with an approximate time to maximum plasma concentration of 1–2 h
Distribution
The mean volume of distribution of atorvastatin is approximately 381 L. It is highly protein bound (=98%), and likely secreted into human breast milk.
8Metabolism
Atorvastatin metabolism is primarily through cytochrome P450 3A4 hydroxylation to form active ortho-and parahydroxylatedmetabolites. The ortho-and parahydroxylatedmetabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxymetabolite undergoes further metabolism via glucuronidation.
9ExcretionAtorvastatin is primarily eliminated via hepatic biliary excretion, with less than 2% recovered in the urine. Bile elimination follows hepatic and/or extrahepaticmetabolism. Atorvastatin has an approximate elimination half-life of 14 h.
10Medical Uses
Hypercholesterolemia to reduce total cholesterol, LDL-C, apo-B, as well as increase HDL levels.
Hypertriglyceridemia
Primary prevention of heart attack, stroke.
Secondary prevention of myocardial infarction, stroke, unstable angina.
Myocardial infarction and stroke prophylaxis in patients with type II diabetesInteractions
Grapefruit juice can increase the blood levels of atorvastatin. This can increase the risk of side effects such as liver damage.
Interactions with clofibrate, fenofibrate, gemfibrozil, usually in combination with statins, increase the risk of myopathy.
Barbiturates, carbamazepine, oxcarbazepine, rifampin, and rifamycin, which are CYP3A4 inducers, can decrease the plasma concentrations of atorvastatin.
12Precautions to be taken Before taking this medicine
Liver disease
Muscle pain or weakness
History of liver disease
History of kidney disease
History of stroke
If you are pregnant or breast-feeding
A thyroid disorder
If you drink more than 2 alcoholic beverages daily.
Side Effects
Cough
Difficulty with swallowing
Fast heartbeat
Fever and dizziness
Itching
Muscle cramps, pain, stiffness, swelling, or weakness
Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
Skin rash
Tightness in the chest
Unusual tiredness or weakness
A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell.Caused by unequal distribution of ions inside vs. outside cell ,Na+ higher outside than inside cell,Ca+ much higher “ “ “ “
K+ higher inside cell than outside Maintenance by ion selective channels, active pumps and exchangers
Definition of arrhythmia - background on cardiac physiology including conduction in heart - action potential - pathogensis of arrhythmia - causes and risk factors for arrhythmia- diagnosis of arrhythmia - symptoms of tachyarrhythmias and bradyarrhythmias - investigations for arrhythmia - treatment of arrhythmia - pharmacological and other modalities of therapy for arrhythmia - managment of different types of arrhythmias
Introduction
Generic Name: Atorvastatin
Brand Names: Lipitor,Atorvast,Divastin,Lipicut
Atorvastatin a group of drugs called HMG CoA reductase inhibitors, or "statins."
Atorvastatin reduces levels of "bad" cholesterol or LDL and triglycerides in the blood, and also increasing levels of "good" cholesterol or HDL.
4Mechanism of action
Statin drugs competitively inhibit HMG-CoA, which is an enzyme that catalyzes the synthesis of HMG-CoA in to cholesterol. Therefore, it effectively the synthesis of new cholesterol. It leads to an increase in LDL receptor on Liver cells to take in more LDL, effectively decreasing LDL in the body
5Pharmacokinetics
Absorption
Atorvastatin undergoes rapid absorption when taken orally, with an approximate time to maximum plasma concentration of 1–2 h
Distribution
The mean volume of distribution of atorvastatin is approximately 381 L. It is highly protein bound (=98%), and likely secreted into human breast milk.
8Metabolism
Atorvastatin metabolism is primarily through cytochrome P450 3A4 hydroxylation to form active ortho-and parahydroxylatedmetabolites. The ortho-and parahydroxylatedmetabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxymetabolite undergoes further metabolism via glucuronidation.
9ExcretionAtorvastatin is primarily eliminated via hepatic biliary excretion, with less than 2% recovered in the urine. Bile elimination follows hepatic and/or extrahepaticmetabolism. Atorvastatin has an approximate elimination half-life of 14 h.
10Medical Uses
Hypercholesterolemia to reduce total cholesterol, LDL-C, apo-B, as well as increase HDL levels.
Hypertriglyceridemia
Primary prevention of heart attack, stroke.
Secondary prevention of myocardial infarction, stroke, unstable angina.
Myocardial infarction and stroke prophylaxis in patients with type II diabetesInteractions
Grapefruit juice can increase the blood levels of atorvastatin. This can increase the risk of side effects such as liver damage.
Interactions with clofibrate, fenofibrate, gemfibrozil, usually in combination with statins, increase the risk of myopathy.
Barbiturates, carbamazepine, oxcarbazepine, rifampin, and rifamycin, which are CYP3A4 inducers, can decrease the plasma concentrations of atorvastatin.
12Precautions to be taken Before taking this medicine
Liver disease
Muscle pain or weakness
History of liver disease
History of kidney disease
History of stroke
If you are pregnant or breast-feeding
A thyroid disorder
If you drink more than 2 alcoholic beverages daily.
Side Effects
Cough
Difficulty with swallowing
Fast heartbeat
Fever and dizziness
Itching
Muscle cramps, pain, stiffness, swelling, or weakness
Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
Skin rash
Tightness in the chest
Unusual tiredness or weakness
dal test manuale al test automatico: un esempio basato sul Keyword Driven Tes...Microfocusitalia
M2A, dal test manuale al test automatico: un esempio basato sul Keyword Driven Testing - Stefano Lontano, Pre Sales Borland Solutions, Micro Focus Italy
רפאל נדלן - מה חשוב שתדעו לפני רכישת קרקע?דוד רפאל
דוד רפאל (קבוצת רפאל נדל"ן) הוא יזם נדל"ן .
מעוניינים בקרקע לדירה בתל אביב החל מ-380,000? צרו קשר לגבי פרויקט מגדלי ההשכלה.
כתובת המשרדים: רחוב שהם 5, בנין פז 1 מתחם הבורסה, רמת גן, קומה 19.
פרטי קשר - דוד רפאל - קבוצת רפאל נדל"ן :
טל: 073-7055771 / 8058*
פקס: 073-7055777
Information Governance (IG) is truly a strategic initiative of any organization. As such, the connection to organizational strategy must be made concretely. The starting point for any IG initiative must be the organization’s corporate mandate, policies and strategic directives, mission and goals. The resulting tactical elements must be aligned with the organizational plans, objectives, and the operational targets of management.
Esitys muuttoliikkeen voittaja- ja häviäjäalueista 2010-luvun Suomessa. Muuttoliike on yksi keskeisistä muutosvoimista, joka muovaa aluerakennetta suoraan ja epäsuoraan. Esityksessä on käyty läpi muuttoliikkeen valikoivuuteen ja polarisoivaan kehitykseen liittyviä piirteitä karttojen, graafien ja taulukoiden avulla.
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.
CLASS I: SODIUM CHANNEL BLOCKERS
Drugs block cardiac sodium channels. So, they decrease conduction velocity in the atria.
This drugs fall into five groups
CLASS I A ; agents delay repolarization
CLASS IB; agents accelerate repolarization
CLASS IC; agents have limited effect on repolarization
This presentation describes cardiac physiology and classification of antiarrhythmics. It also includes a brief account of main drugs of each group including latest drugs like ranolazine, ivabradine and vernakalent.
This is A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias,
This PPT covers: Introduction, Generic Name/Trade name, Mechanism of Action, Pharmacological class, Pharmacodynamics, Metabolism, therapeutic uses, Dosage, Adverse Effect, Precautions & Drug interaction and Contraindication
This PPT Under supervisors Drs in FUE Pharmacy
Written By a Pharmacy Student Ahmed Yehia Abu El-Naga
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
1. ANTIARITMIA
Oleh :
Dimas P.Nugraha
Bagian Farmakologi FK UR
2.
3. Abnormal automaticity
Effect of drugs on automaticity
Abnormalities in impulse conduction
Effects of drugs on conduction abnormalities
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15. Quinidine
Quinidine is the prototype.
Because of its concomitant Class III activity, it
can actually precipitate arrhythmias such as
polymorphic ventricular tachycardia (torsades
de pointes), which can degenerate into
ventricular fibrillation.
Because of the toxic potential of quinidine,
calcium antagonists, such as amiodarone and
verapamil, are increasingly replacing this drug in
clinical use.
16. Mechanism of action:
Quinidine binds to open and inactivated sodium
channels and prevents sodium influx, thus
slowing the rapid upstroke during Phase 0.
It also decreases the slope of Phase 4
spontaneous depolarization and inhibits
potassium channels.
17. Therapeutic uses:
Quinidine is used in the treatment of a wide
variety of arrhythmias, including atrial, AV-
junctional, and ventricular tachyarrhythmias.
Quinidine is used to maintain sinus rhythm
after direct-current cardioversion of atrial
flutter or fibrillation and to prevent frequent
ventricular tachycardia
18.
19. Pharmacokinetics:
Quinidine sulfate is rapidly and almost
completely absorbed after oral
administration.
It undergoes extensive metabolism by the
hepatic cytochrome P450 enzymes, forming
active metabolites.
20. Adverse effects:
Arrhythmia (torsades de pointes).
SA and AV block or asystole. At toxic levels, the
drug may induce ventricular tachycardia.
Cardiotoxic effects are exacerbated by
hyperkalemia.
Nausea, vomiting, and diarrhea are commonly
observed.
Large doses may induce the symptoms of
cinchonism (for example, blurred vision, tinnitus,
headache, disorientation, and psychosis)
21. Procainamide
A derivative of the local anesthetic procaine,
shows actions similar to those of quinidine.
Pharmacokinetics: is well-absorbed following oral
administration. The iv route is rarely used, because
hypotension occurs if the drug is infused too rapidly.
Adverse effects: With chronic use, causes a high
incidence of side effects→ a reversible lupus
erythematosus“like syndrome (25 to 30 % of patients).
Toxic concentrations → cause asystole or induction of
ventricular arrhythmias. CNS side effects include
depression, hallucination, and psychosis.
22. Disopyramide
Actions: shows actions similar to those of quinidine.
Disopyramide → a negative inotropic effect that is greater than
quinidine and procainamide, disopyramide causes peripheral
vasoconstriction. The drug may produce a clinically important
decrease in myocardial contractility in patients with preexisting
impairment of left ventricular function. Disopyramide is used in
the treatment of ventricular arrhythmias as an alternative to
procainamide or quinidine. Like procainamide and quinidine, it
also has Class III activity.
Pharmacokinetics: Approximately half of the orally ingested drug
is excreted unchanged by the kidneys. Approximately 30 percent
of the drug is converted by the liver to the less active mono-N-
dealkylated metabolite.
Adverse effects: Disopyramide shows effects of anticholinergic
activity (for example, dry mouth, urinary retention, blurred vision,
and constipation).
23. Lidocaine
Actions: Lidocaine, a local anesthetic,
shortens Phase 3 repolarization and
decreases the duration of the action
potential.
Therapeutic uses: Lidocaine is useful in
treating ventricular arrhythmias arising
during myocardial ischemia, such as during a
myocardial infarction
24. Pharmacokinetics: given intravenously because of
extensive first-pass transformation by the liver, which
precludes oral administration→ dealkylated and
eliminated almost entirely by the liver; consequently,
dosage adjustment → in patients with liver
dysfunction or those taking drugs that lower hepatic
blood flow, such as propranolol.
Adverse effects: It shows little impairment of left
ventricular function and has no negative inotropic
effect. CNS effects → drowsiness, slurred speech,
paresthesia, agitation, confusion, and convulsions.
Cardiac arrhythmias may also occur.
25. Mexiletine
These Class IB drugs have actions similar to
those of lidocaine, and they can be administered
orally.
used for chronic treatment of ventricular
arrhythmias associated with previous
myocardial infarction.
Tocainide
Used for treatment of ventricular
tachyarrhythmias.
Pulmonary toxicity, which may lead to
pulmonary fibrosis.
26.
27. Flecained
Actions:
- suppresses Phase 0 upstroke in Purkinje and
myocardial fibers→slowing of conduction in all
cardiac tissue.
- Automaticity ↓ by an increase in the threshold
potential rather than a decrease in the slope of Phase
4 depolarization.
Therapeutic uses:
→ treating refractory ventricular arrhythmias.
→ particularly useful in suppressing premature
ventricular contraction.
→ negative inotropic effect and can aggravate
congestive heart failure.
28. Pharmacokinetics: absorbed orally,
undergoes minimal biotransformation, and
has a half-life of 16 to 20 hours.
Adverse effects:can cause dizziness, blurred
vision, headache, and nausea. Like other
Class IC drugs→ can aggravate preexisting
arrhythmias or induce life-threatening
ventricular tachycardia that is resistant to
treatment
29. Propafenone
Shows actions similar to those of flecainide.
Propafenone like flecainide, slows
conduction in all cardiac tissues and is
considered to be a broad-spectrum
antiarrhythmic agent
30.
31.
32. Class II agents are -adrenergic antagonists.
These drugs diminish Phase 4 depolarization,
thus depressing automaticity, prolonging AV
conduction, and ↓ heart rate and
contractility.
Class II agents are useful in treating
tachyarrhythmias caused by↑sympathetic
activity. Also used for atrial flutter and
fibrillation and for AV-nodal reentrant
tachycardia.
33. Propranolol
→Reduces the incidence of sudden arrhythmic death after
myocardial infarction (the most common cause of death in
this group of patients).
→The mortality rate in the first year after a heart attack is
significantly reduced by propranolol, partly because of its
ability to prevent ventricular arrhythmias.
Metoprolol
→Beta-adrenergic antagonist most widely used in the
treatment of cardiac arrhythmias.
→Compared to propranolol, it reduces the risk of
bronchospasm.
Esmolol
→a very short-acting beta-blocker used for intravenous
administration in acute arrhythmias that occur during
surgery or emergency situations.
34. Amiodarone
Actions:
contains iodine and is related structurally to thyroxine.
It has complex effects, showing Class I, II, III, and IV actions.
Its dominant effect is prolongation of the action potential
duration and the refractory period.
Amiodarone has antianginal as well as antiarrhythmic
activity.
Therapeutic uses:
Amiodarone is effective in the treatment of severe
refractory supraventricular and ventricular
tachyarrhythmias.
Despite its side-effect profile, amiodarone is the most
commonly employed antiarrhythmic
35. Pharmacokinetics:
incompletely absorbed after oral administration. The drug is unusual
in having a prolonged half-life of several weeks, and it distributes
extensively in adipose issue. Full clinical effects may not be achieved
until 6 weeks after initiation of treatment.
Adverse effects:
shows a variety of toxic effects. After long-term use, more than half
of patients receiving the drug show side effects that are severe
enough to prompt its discontinuation..
Some of the more common effects include interstitial pulmonary
fibrosis, gastrointestinal tract intolerance, tremor, ataxia, dizziness,
hyper- or hypothyroidism, liver toxicity, photosensitivity,
neuropathy, muscle weakness, and blue skin discoloration caused by
iodine accumulation in the skin.
recent clinical trials have shown that amiodarone does not reduce
the incidence of sudden death or prolong survival in patients with
congestive heart failure
36. Sotalol
A class III antiarrhythmic agent, also has potent nonselective Beta-
blocker activity. It is well established that beta blockers reduce mortality
associated with acute myocardial infarction.
Actions: blocks a rapid outward potassium current, known as the delayed
rectifier. This blockade prolongs both repolarization and duration of the
action potential, thus lengthening the effective refractory period.
Therapeutic uses:
used for long-term therapy to decrease the rate of sudden death
following an acute myocardial infarction. have a modest ability to
suppress ectopic beats and to reduce myocardial oxygen demand.
strong antifibrillatory effects, particularly in the ischemic myocardium.
Sotalol was more effective in preventing recurrence of arrhythmia and in
decreasing mortality than imipramine, mexiletine, procainamide,
propafenone, and quinidine in patients with sustained ventricular
tachycardia
37. Adverse effects:
This drug also has the lowest rate of acute or
long-term adverse effects
prolong the QT interval
the syndrome of torsade de pointes is a
serious potential adverse effect, typically
seen in three to four percent of patients
38.
39. Dofetilide
Can be used as a first-line antiarrhythmic agent in patients
with persistent atrial fibrillation and heart failure or in those
with coronary artery disease with impaired left ventricular
function.
Because of the risk of proarrhythmia, dofetilide initiation is
limited to the inpatient setting and is restricted to
prescribers who have completed a specific manufacturer's
training session.
Along with amiodarone and Beta-blockers, dofetilide is the
only antiarrhythmic drug that is recommended by experts
for the treatment of atrial fibrillation in a wide range of
patients.
40. Class IV drugs are calcium-channel blockers .
They decrease the inward current carried by
calcium, resulting in a decreased rate of Phase 4
spontaneous depolarization.
They also slow conduction in tissues that are
dependent on calcium currents, such as the AV
node.
Although voltage-sensitive calcium channels
occur in many different tissues, the major effect
of calcium-channel blockers is on vascular smooth
muscle and the heart.
41. Verapamil and diltiazem
Actions:
Calcium enters cells by voltage-sensitive
channels and by receptor-operated channels
that are controlled by the binding of agonists,
such as catecholamines, to membrane
receptors.
Calcium-channel blockers, such as verapamil
and diltiazem, are more effective against the
voltage-sensitive channels, causing a decrease in
the slow inward current that triggers cardiac
contraction
42.
43. Therapeutic uses:
Verapamil and diltiazem are more effective against
atrial than against ventricular arrhythmias. They are
useful in treating reentrant supraventricular
tachycardia and in reducing the ventricular rate in
atrial flutter and fibrillation. In addition, these drugs
are used to treat hypertension and angina.
Pharmacokinetics:
Verapamil and diltiazem are absorbed after oral
administration.
Verapamil is extensively metabolized by the liver;
thus, care should be taken when administering this
drug to patients with hepatic dysfunction.
44. Adverse effects:
Verapamil and diltiazem have negative
inotropic properties and, therefore, may be
contraindicated in patients with preexisting
depressed cardiac function.
Both drugs can also produce a decrease in
blood pressure because of peripheral
vasodilation an effect that is actually beneficial
in treating hypertension
45. Digoxin
Shortens the refractory period in atrial and
ventricular myocardial cells while prolonging the
effective refractory period and diminishing
conduction velocity in the AV node.
Used to control the ventricular response rate in
atrial fibrillation and flutter.
At toxic concentrations, digoxin causes ectopic
ventricular beats that may result in ventricular
tachycardia and fibrillation. [Note: This arrhythmia
is usually treated with lidocaine or phenytoin.]
46. Adenosine
Adenosine is a naturally occurring nucleoside,
but at high doses, the drug decreases
conduction velocity, prolongs the refractory
period, and decreases automaticity in the AV
node.
Intravenous adenosine is the drug of choice for
abolishing acute supraventricular tachycardia.
It has low toxicity but causes flushing, chest
pain, and hypotension. Adenosine has an
extremely short duration of action
(approximately 15 seconds).
47.
48.
49.
50. The margin between efficacy and toxicity is
particularly narrow for antiarrhythmic drugs.
Risks and benefits must be carefully considered
51. 1. Eliminate the cause.
Precipitating factors must be recognized and
eliminated if possible.
These include not only abnormalities of internal
homeostasis, such as hypoxia or electrolyte
abnormalities (especially hypokalemia or
hypomagnesemia), but also drug therapy and
underlying disease states such as hyperthyroidism or
cardiac disease.
It is important to separate this abnormal substrate
from triggering factors, such as myocardial ischemia
or acute cardiac dilation, which may be treatable and
reversible
52. 2. Make a firm diagnosis.
A firm arrhythmia diagnosis should be
established.
For example, the misuse of verapamil in patients
with ventricular tachycardia mistakenly diagnosed
as supraventricular tachycardia can lead to
catastrophic hypotension and cardiac arrest.
As increasingly sophisticated methods to
characterize underlying arrhythmia mechanisms
become available and are validated, it may be
possible to direct certain drugs toward specific
arrhythmia mechanisms
53. 3. Determine the baseline condition
Underlying heart disease is a critical determinant of drug
selection for a particular arrhythmia in a particular patient. A key
question is whether the heart is structurally abnormal.
Few antiarrhythmic drugs have documented safety in patients
with congestive heart failure or ischemic heart disease.
some drugs pose a documented proarrhythmic risk in certain
disease states, eg, class 1C drugs in patients with ischemic heart
disease. A reliable baseline should be established against which
to judge the efficacy of any subsequent antiarrhythmic
intervention.
Several methods are now available for such baseline
quantification → prolonged ambulatory
monitoring, electrophysiologic studies that reproduce a target
arrhythmia, reproduction of a target arrhythmia by treadmill
exercise, or the use of transtelephonic monitoring for recording
of sporadic but symptomatic arrhythmias
54. 4. Question the need for therapy
The mere identification of an abnormality of
cardiac rhythm does not necessarily require
that the arrhythmia be treated.
An excellent justification for conservative
treatment was provided by the Cardiac
Arrhythmia Suppression Trial (CAST) referred
to earlier.
55. The benefits of antiarrhythmic therapy are
actually relatively difficult to establish.
Two types of benefits can be envisioned:
reduction of arrhythmia-related symptoms, such
as palpitations, syncope, or cardiac arrest; or
reduction in long-term mortality in asymptomatic
patients.
Among drugs discussed here, only blockers have
been definitely associated with reduction of
mortality in relatively asymptomatic patients,
and the mechanism underlying this effect is not
established
56. Several specific syndromes of arrhythmia
provocation by antiarrhythmic drugs have also
been identified, each with its underlying
pathophysiologic mechanism and risk factors.
Drugs such as quinidine, sotalol, ibutilide, and
dofetilide, which act—at least in part—by
slowing repolarization and prolonging cardiac
action potentials, can result in marked QT
prolongation and torsade de pointes
57. The urgency of the clinical situation determines the
route and rate of drug initiation. When immediate
drug action is required, the intravenous route is
preferred.
Therapeutic drug levels can be achieved by
administration of multiple intravenous boluses.
Drug therapy can be considered effective when the
target arrhythmia is suppressed (according to the
measure used to quantify it at baseline) and toxicities
are absent
58. Monitoring plasma drug concentrations can be a
useful adjunct to managing antiarrhythmic
therapy.
Plasma drug concentrations are also important
in establishing compliance during long-term
therapy as well as in detecting drug interactions
that may result in very high concentrations at
low drug dosages or very low concentrations at
high dosages.