Cardiovascular pharmacology
Cardiovascular (=Circulatory) system – heart and blood vessels
Arteries – transport blood to tissues
Capillaries – sites of exchange, fluid O2, CO2, nutrients etc.
Venules – collect blood from capillaries
Veins – transport blood back to heart
Blood moves within vessels – higher pressure to lower pressure
Resistance to flow depends on vessel diameter, length and viscosity of blood
Cardiovascular pharmacology
Cardiovascular (=Circulatory) system – heart and blood vessels
Arteries – transport blood to tissues
Capillaries – sites of exchange, fluid O2, CO2, nutrients etc.
Venules – collect blood from capillaries
Veins – transport blood back to heart
Blood moves within vessels – higher pressure to lower pressure
Resistance to flow depends on vessel diameter, length and viscosity of blood
principle action of drugs,types of angina classification of drugs ,nitrates,calcium channel blockers pharmacological actions ,combination therapy and its sid effects
PH1.28 Describe the mechanisms of action, types, doses, side effects, indicat...Dr Pankaj Kumar Gupta
PH1.28 Describe the mechanisms of action, types, doses, side effects, indications and contraindications of the drugs used in ischemic heart disease (stable, unstable angina and myocardial infarction), peripheral vascular disease
A Power point presentation on Betalactam antibiotics suitable for undergraduate medical students. This Ppt is already presented in theory class lectures to the students of NEIGRIHMS, Shillong, Meghalaya
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
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
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
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
- 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
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.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
Are There Any Natural Remedies To Treat Syphilis.pdf
Antianginal drugs and drugs used in ischaemia - drdhriti
1. Antianginal Drugs
Dr. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong
2. What is angina?
• Angina pectoris is a syndrome characterized by
sudden severe pressing substernal chest pain or
heaviness radiating to the neck, jaw, back and
arms. It is often associated with diaphoresis,
tachypnoea and nausea
• Primary cause: imbalance between myocardial
oxygen demand and oxygen supplied by coronary
vessels
– This imbalance may be due to:
1. a decrease in myocardial oxygen delivery
2. an increase in myocardial oxygen demand, or both
• The discomfort abates when supply becomes
adequate for demand. Typically angina lasts for
seconds to minutes, up to 15 minutes
3. Factors affecting Myocardial
Oxygen Delivery
• Coronary artery blood flow is the primary determinant of
oxygen delivery to the myocardium
– Myocardial oxygen extraction from the blood is nearly
complete, even at rest
• Coronary blood flow is essentially negligible during systole
and is therefore determined by:
– Perfusion pressure during diastole
– Duration of diastole
– Coronary vascular resistance: determined by numerous factors:
• Atherscelorosis
• Intracoronary thrombi
• Metabolic products that vasodilate coronary arterioles
• Autonomic activity
• Extravascular compression
4. Factors Affecting
Myocardial Oxygen Demand
• The major determinants of myocardial oxygen
consumption include:
1. Ventricular wall stress
• Both preload (end-diastolic pressure) and afterload (end-
systolic pressure) affect ventricular wall stress
2. Heart rate
3. Myocardial metabolism (glucose vs fatty acids)
• A commonly used non-invasive index of
myocardial oxygen demand is the “double
product”:
– [Heart rate] X [Systolic blood pressure]
– Also known as the “rate pressure product”
5. Types of Angina
1. Classical angina:
Stable
2. Variant or Prinzmetal`s angina
Unstable
Myocardial infarction – what is it ?
• Ischaemic necrosis of a portion of myocardium due to
acute and complete occlusion of a coronary artery -
due to coronary thrombosis
6. Stable Angina
• Common form and is also known as - exertional angina/typical or classic
angina/angina of effort/atherosclerotic angina
– The underlying pathology is usually atherosclerosis (reduced oxygen delivery)
giving rise to ischemia under conditions where the work load on the heart
increases (increased oxygen demand)
– Anginal episodes can be precipitated by exercise, cold, stress, emotion, or
eating
– Subendocardial crunch developes
• Therapeutic goals:
– Increasing myocardial blood flow by dilating coronary arteries and arterioles
(increase oxygen delivery)
– Decreasing cardiac load (preload and afterload: decrease oxygen demand)
– Decreasing heart rate (decrease oxygen demand)
7. Unstable Angina
• Unstable angina is also known as:
– Preinfarction angina/Crescendo angina/angina at rest
• Associated with a change in the character, frequency, and
duration of angina in patients with stable angina, and
episodes of angina at rest
• Caused by recurrent episodes of small platelet clots at the
site of a ruptured atherosclerotic plaque which can also
precipitate local vasospasm
• May be associated with myocardial infarction
• Therapeutic Goal: Inhibiting platelet aggregation and
thrombus formation (increase oxygen delivery), decreasing
cardiac load (decrease oxygen demand), and vasodilate
coronary arteries (increase oxygen delivery)
8. Vasospastic
Angina
• Vasospastic angina (uncommon form) is also known as:
– Variant angina/Prinzmetal's angina
• Caused by transient vasospasm of the coronary vessels
• Attack occurs even at rest or during sleep
• Usually associated with underlying atheromas, abnormally
reactive or hypertrophied segments in coronary artery
• Chest pain may develop at rest
• Therapeutic rationale: Decrease vasospasm of coronary
vessels (calcium channel blockers are efficacious in >70% of
patients; increase oxygen delivery)
9. Coronary
artery image
• Coronary calibre
changes in Classical
and variant angina
1. Normal
2. Classical angina
3. Variant angina
1.
2.
3.
10. Classification of Antianginal Agents
1. Nitrates:
a) Short acting (10 minutes): Glyceryl trinitrate (GTN and
Nitroglycerine) - EMERGENCY
b) Long acting (1 Hour): Isosorbide dinitrate, Isosorbide mononitrate,
Erythrityl tetranitrate, Pentaerythritol tetranitrate
2. Calcium Channel Blockers:
a) Phenyl alkylamine: Verapamil
b) Benzothiazepin: Diltiazem
c) Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine
and Nimodipine
3. Beta—adrenergic Blockers: Propranolol, Metoprolol, Atenolol and
others
4. Potassium Channel openers: Nicorandil
5. Others: Dipyridamole, Trimetazidine, Ranolazine and oxyphedrine
11. Actions of Nitrates - GTN
1. Preload reduction:
Dilatation of veins more than arteries – peripheral pooling of Blood –
decrease venous return
Reduction in preload – decreased end diastolic size – decrease in
fibre length
Less wall tension to develop for ejection (Laplace`s law) – less oxygen
consumption and reduction in ventricular wall pressure (crunch
abolished)
2. Afterload reduction:
Some amount of arteriolar dilatation – Decrease in peripheral
Resistance (afterload reduction) – reduction in Cardiac work (also fall
in BP)
Standing posture – pooling of Blood in legs – reflex tachycardia
(prevented by lying down and foot end raising)
However in large doses opposite happens – marked fall in BP – reflex
tachycardia – increased cardiac work – precipitation of angina
12. Actions of Nitrates - contd.
3. Increased Myocardial Perfusion:
Redistribution of coronary blood flow – facilitates entry of
blood to Ischaemic area
However, total blood flow in coronary vessels is almost
unchanged with Nitrates
4. Mechanism of angina relief:
Variant angina – coronary vasodilatation
Classical angina – reduction in Cardiac load
Increased exercise tolerance
5. Other actions: Cutaneous vasodilatation (flushing),
meningeal vessels dilatation (headache) and decreased
splanchnic and Renal blood flow (compensatory)
13. Mechanism of Action of Nitrovasodilators
Nitric Oxide
activates
converts
Guanylate Cyclase*
GTP
cGMP
activates
cGMP-dependent protein kinase
Activation of PKG results in dephosphorylation
of several proteins that reduce intracellular calcium
causing smooth muscle relaxation
Nitrates become denitrated by glutathione S-transferase
to release
Dephosphorylaton of
MLCK
14. Pharmacokinetics - Nitrates
• All Nitrates share same action – only Pharmacokinetic differences
• All are highly lipid soluble and absorbed well from bccal mucosa, orally
and skin
• Rapidly denitrated by glutathione reductase and mitochondrial aldehyde
dehydrogenase
• Hepatic first-pass metabolism is high and oral bioavailability is low for
nitroglycerin (GTN) and isosorbide dinitrate (ISDN)
– Sublingual or transdermal administration - avoids the first-pass effect
• Isosorbide mononitrate is not subject to first-pass metabolism and is 100%
available after oral administration
• Hepatic blood flow and disease can affect the pharmacokinetics of GTN
and ISDN
15. GTN ISDN 5-ISMN
Half-life (min) 3 10 280
Plasma clearance (L/min) 50 4 0.1
Apparent volume of distribution (L/kg) 3 4 0.6
Oral bioavailability (%) < 1 20 100
Property
Comparison of
Pharmacokinetic
Properties of Nitrates
16. Nitrates - ADRs
• Due to excessive vasodilatation - Orthostatic
hypotension, Tachycardia, Severe throbbing
headache, Dizziness, Flushing and Syncope
• Methaemoglobinemia
• Rashes - rare
• Contraindicated in patients with elevated
intracranial pressure
• Drug Interaction: Sildenafil (Viagra) and other PDE-5
inhibitors used for erectile dysfunction can
potentiate the actions of nitrates because they
inhibit the breakdown of cGMP (they should not be
taken within 6 hours of taking a nitrovasodilator)
17. Nitrate Tolerance
• Continuous or frequent exposure to nitrates can
lead to the development of complete tolerance
• The mechanism of tolerance is not completely
understood:
– May be related to the enzymes involved in converting
the nitrates to NO
– or to the enzyme that produces cGMP
• Industrial (occupational) exposure to organic
nitrates has been associated with “Monday
disease” and physical dependence manifest by
variant angina occurring 1-2 days after
withdrawal
18. Nitrates – Individual agents
• Glyceryl trinitrate (GTN, Nitroglycerine):
– Rendered nonexplosive by adsorbing in inert matrix of a
tablet
– Stored in a tightly closed Glass container
• Formulations: Oral, SL, IV and ointment
1) SL (0.5 mg) – to terminate an Ongoing attack
• Crushed under the tongue and spread over the buccal mucosa
• Action starts within 1-2 minutes
• Effects disappear within minutes but its metabolite – dinitrate
stays (1 hr)
2) IV transfusion: in acute AMI
3) Patches: Ointment and patches – at night application
19. Nitrates – Therapeutic Uses
1. Angina pectoris: Classical and variant Types
2. Acute Coronary syndromes: Unstable angina and associated with
MI (Combination Drugs)
3. Myocardial Infarction: In evolving MI : IV administration is useful
in relieving – 3 things: chest pain, congestions of chest and
reducing the infarct size favouring blood supply to ischemic zone
4. CHF and LVF: Pooling of blood
5. Biliary colic: Sl administration
6. Oesophageal spasm: Reduction in oesophageal tone (achalasia)
7. Cyanide Poisoning: Nitrates counter cyanide by producing
Methaemoglobin – then Cyanomethaemoglobin (Sod. Thiosulfate
is given to form Sod. Thiocyanate)
20. Role of Beta-blockers
• No coronary vasodilatation like the
nitrovasodilators or calcium channel blockers -
beta-blockers are important in the treatment of
angina
• Instead coronary flow reduced – beta2 effect
• But, Coronary flow to ischaemic area not
reduced:
– Redistribution and decrease in ventricular wall
tension
• Improve myocardial perfusion by slowing heart rate (more
time spent in diastole)
• less O2 consumption (decreased HR, Inotropy and mean BP)
21. Role of Beta-blockers – contd.
• Benefits:
– Decreased frequency and severity of attacks
– Increased exercise tolerance (classical angina) – cardioselectives are
preferred (coronary spasm due to alpha-blockade)
– Lowers sudden cardiac death
– Routinely used in UA and with MI – pretreatment with Nitrates or CCB
– Avoid abrupt withdrawal
• ADRs and CI:
– May exacerbate heart failure
– Contraindicated in patients with asthma
– Precaution in diabetes since hypoglycemia-induced tachycardia can be
blunted or blocked
– May depress contractility and heart rate and produce AV block in
patients receiving non-dihydropyridine calcium channel blockers (i.e.
verapamil and diltiazem)
22. Calcium Channels
1. Voltage Sensitive Channels (-
40mV)
2. Receptor operated Channel (Adr
and other agonists)
3. Leak channel (Ca++ATPase)
o Voltage sensitive Calcium
channels are
heterogenous (membrane
spanning funnel shaped):
o L-Type (Long lasting
current) – SAN, AVN,
Conductivity, Cardiac and
smooth muscle
o T-Type (Transient Current) –
Thalumus, SAN
o N-Type (Neuronal) – CNS,
sypmathetic and myenteric
plexuses
24. Effects on Vascular Smooth Muscle
• Ca++ channel blockers inhibit mainly L-type
• Little or no effect on receptor-operated channels or on
release of Ca++ from SR
1. Decreased intracellular Ca++ in arterial smooth muscle results
in relaxation (vasodilatation) -> decreased cardiac afterload
(aortic pressure)
2. Little or no effect on venous beds -> no effect on cardiac
preload (ventricular filling pressure)
DHPs have the highest vascular SM relaxant action
3. Additional Mechanism: Release of NO – inhibit cAMP PDE –
increased SM cAMP
• Specific dihydropyridines may exhibit greater potencies in
some vascular beds (e.g.- nimodipine more selective for
cerebral blood vessels, nicardipine for coronary vessels)
• Little or no effect on nonvascular smooth muscle except
bronchial, uterine, biliary, vesical and intestinal
25. Effects on
Cardiac Cells
• Negative Inotropic, Chronotropic and Dromotropic
• Negative inotropic effect (myocardial L-type channels) –
WMC and ventricular fibres
• Negative chronotropic /dromotropic effects (L- and T-type
channels)
• Verapamil and diltiazem shows such effects but not DHPs
• Verapamil, diltiazem, and mibefradil depress SA node and AV
conduction – depression of pacemaker and conduction
• Dihydropyridines have minimal direct effects on SA node
and AV conduction – more selective for vascular smooth
muscles
• Magnitude and pattern of cardiac effects depends on
the class of Ca++channel blocker
Recovery
Resting Activated Inactivated
Nonconducting of C++ conducting Ca++ NC Ca++
26. Relative Cardiovascular Effects of Calcium
Channel Blockers - (Goodman & Gilman)
Verapamil ++++ ++++ +++++ +++++
Diltiazem +++ ++ +++++ ++++
Nifedipine +++++ + + 0
Nicardipine +++++ 0 + 0
Compound Coronary
vasodilatation
Suppression
of cardiac
contractility
Suppression
of
SA node
Suppression
of
AV node
27. Adverse effects
• Verapamil:
– Nausea, constipation and bradycardia
– Headache, flushing and oedema – less common
– Hypotension and tachycardia - less common
– Precipitation of CHF in pre-existing patients
– Increase in plasma digoxin level
– Contraindicated in 2nd and 3rd degree heart block
• Diltiazem: Same as Verapamil
28. Adverse effects – contd.
• DHP – immediate release forms e.g. Nifedepine:
– Palpitation, flushing ankle oedema, hypotension, headache
and drowsiness
– Diuresis
– Higher incidence of frequency of angina
– Higer incidence of mortality
– Voiding difficulty (relaxed bladder Vs increased urine)
• Nifedipine may increase mortality in patients with
myocardial ischemia
– Cause increase in angina frequency (myocardial
Ischaemia)
– Cerebral Ischaemia – rapid bringing down of BP
– Bladder relaxation – voiding difficulty
– Decrease in Insulin release
29. CCBs - Pharmacokinetics
• High oral absorption, but high first pass metabolism (except amlodipine) –
inter and intra individual variation and highly plasma protein bound
• Extensively distributed in tissues and highly metabolized in liver and
excreted in urine, eliminated in 2 - 6 Hrs (except amlodipine)
Drug Bioavailability
%
Vd (L/kg) Active
metabolite
Elim half life(hr)
Verapamil 15-30 5.0 Y 4-6
Diltiazem 40-60 3.0 Y 5-6
Nifedepine 30-60 0.8 M 2-5
Felodipine 15-25 10.0 None 12-18
Amlodipine 60-65 21.0 None 35-45
30. Desired Therapeutic Effects of Calcium
Channel Blockers for Angina
• Improve oxygen delivery to ischemic
myocardium
– Vasodilate coronary arteries
– Particularly useful in treating vasospastic angina
• Reduce myocardial oxygen consumption
– Decrease afterload (no effect on preload)
– Non-dihydropyridines also lower heart rate and
decrease contractility
– (* Dihydropyridines may aggravate angina in some
patients due to reflex increases in heart rate and
contractility)
31. CCBs – Therapeutic Uses
1. Angina Pectoris:
Reduce frequency and severity of Classical and Variant
angina
Classical angina
• reduction in cardiac work by reducing afterload
• Increased exercise tolerance
• Coronary flow increase – less significant (fixed arterial block)
• But: short acting DHPs cause Myocardial Ischaemia – WHY? -
due to decreased coronary blood flow secondary to fall in mean
BP, reflex tachycardia and coronary steal
• Verapamil/Diltiazem a reduce O2 consumption by direct effect –
do not aggravate angina
MI - Verapamil/Diltiazem as alternative to β-blockers
Variant angina: Benefited by reducing the arterial spasm
32. CCBs – Therapeutic Uses – contd.
2. Hypertension
3. Cardiac arrhythmia
4. Hypertrophic Cardiomyopathy: verapamil
5. Nifedipine – Preterm labour (?) and
Raynaud`s disease; Verapamil - migraine and
nocturnal leg cramps
33. Pharmacotherapy of Angina Pectoris
• Aim: 1. Relief and prevention of Individual attack; 2. Chronic Prophylaxis; 3.
Measures to prevent Progression
1. Prevention of Individual attack:
• Short acting Nitrate as and when required basis
• GTN is the drug of Choice in all kinds of angina
• Dose: 0.3 – 0.6 mg SL
• If symptoms not relieved quickly – additional tabs at 5 min. interval (not more than 3 tabs at 5
minutes interval)
• Discard the remnant tab soon relieved – hypotension
2. Acute Prophylaxis: GTN 15 minutes before a period of increased activity –
exercise, sexual activity etc. – lasts for upto 2 Hrs
3. Chronic Prophylaxis:
• Monotherapy with either of the 3 groups of Drugs – depends on stage and associated
cardiac disease
• May be Nitrates/Ca++ blockers /beta-blockers – beta blockers are preferred
• When Monotherapy fails: Go for combination of those Drugs (two drugs)
• Beta blocker + nitrates or slow acting DHP + beta blocker (no diltiazem or verapamil)
• CCB + Nitrates
• In severe cases - nitrates+ CCBs + beta blockers
34. Combination Therapy of Angina
• Use of more than one class of antianginal agent can reduce specific
undesirable effects of single agent therapy
Nitrates Alone
Reflex Increase
Decrease
Decrease
Reflex increase
Decrease
Beta-Blockers or
Channel Blockers
Alone
Decrease*
Decrease
Increase
Decrease*
Increase
Nitrates Plus
Beta-Blockers or
Channel Blockers
Decrease
Decrease
None or decrease
None
None
Undesireable effects are shown in italics
* Dihydropyridines may cause the opposite effect due to a reflex increase
in sympathetic tone
Heart Rate
Afterload
Preload
Contractility
Ejection time
Effect
35. Potassium Channel Openers –
Nicorandil
• Minoxidil and diazoxide
• MOA:
– Activation of ATP sensitive K+ channel – hyperpolarization of vascular
smooth muscle – relaxation of Smooth muscle
– Also acts as NO donor and increases cGMP – Arterio-venous relaxation
– Dilatation of all types of coronary vessels – epicardial and deep
• Benefits in angina (equipotent to nitrates, beta blockers and Ca++
channel blockers)
– Reduced angina frequency
– Increased exercise tolerance
– Ischaemic preconditioning for Myocardial stunning , arrhythmia and
infarct size (Mitochondrial K+ATP channel opening)
• ADRs: Flushing, palpitation, nausea, vomiting, aphthous ulcer
• Dose: available as 5, 10 mg tabs and also injection
36. Pharmacotherapy
of MI
1. Aim:
Emergency life saving management of the patient (ICU)
Subsequent Treatments
2. Pain, anxiety and apprehension: Morphine, Pethidine parenteral
3. Oxygenation: assisted respiration
4. Maintenance of Blood Volume, tissue perfusion and microcirculation: slow IV
fluid with saline
5. Correction of acidosis: Sodibicarb IV
6. Prevention of Arrhythmia: Beta blockers early (arrhythmia and infarct size)
7. Pump Failure: Furosemide, GTN IV/Nitroprusside and Dobutamine
8. Prevention of Thrombus extension and thrombo-embolism: Aspirin and oral
anticoagulants
9. Thrombolysis and reperfusion: Streptokinase, urokinase etc.
10. Prevention of Remodelling
11. Prevention of future attacks: beta-blockers, aspirin, anti-hyperlipidemia
37. Peripheral Vascular Disease –
Pentoxiphylline (Trental) -
• Analogue of Theophylline – PDE inhibitor
• Action:
– Reduction of whole blood viscosity by improving the flexibility of RBCs
– Improvement of passage of blood through microcirculation
– No vasodilatation but improved circulation
– Less chance of steal phenomenon
• Kinetics: Well absorbed in the GI tract, Metabolized in liver and via erythrocytes -
some metabolites are active. Undergoes extensive 1st pass metabolism, excreted
in urine
• Available in tabs – 400 mg form and also injection
• Uses: 1) Non-haemorrhagic stroke 2) Intermittent claudication 3) Trophic leg
ulcers 4) TIA 5) To improve memory, vertigo and tinnitus etc. after CVA
38. What is Important?
• Mechanism of action, therapeutic uses and
ADRs of Nitrates
• Role of Nitrates in Angina Pectoris
• Role of Beta-blockers and Ca++ channel
blockers in Angina Pectoris
• Pharmacotherapy of Angina Pectoris
• Pharmacotherapy of Myocardial Infarction
• Potassium Channel Openers – short question
Editor's Notes
The coronary perfusion pressure is the difference between the aortic diastolic pressure and left ventricular end-diastolic pressure (LVEDP)
Balance between Oxygen and fatty acid for production of ATP in heart. When Oxygen reduces in heart (post ischemia) increased fatty acid oxidation for ATP production which require more oxygen --- more demand