This document provides an overview of the pharmacological management of congestive heart failure. It discusses the pathophysiology of heart failure and compensatory mechanisms. It describes the renin-angiotensin-aldosterone system and its role in heart failure. The document outlines the classification, causes, signs and symptoms, and diagnostic criteria of heart failure. It discusses the goals and types of drugs used to treat heart failure, including vasodilators, diuretics, beta blockers, and angiotensin-modulating agents like ACE inhibitors. The document provides details on commonly used ACE inhibitors and their mechanisms and effects in treating heart failure.
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid.
It is an immunosuppressant drug combined with drugs such as Cyclosporine.
They are specific 5-HT and various degrees NE reuptake inhibition.
Venlafaxine, at lower doses (75–100 mg/day) acts as SSRI. As the dose increases it inhibit NE reuptake (& 2ry ↓ DA reuptake in prefrontal cortex, which lacks DAT→ ↑ DA).
This presentation was delivered over two days to second year pharmacy students enrolled in a course in pharmacology & toxicology. This lecture is designed to accompany Goodman & Gilman's (12e) chapter 11.
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid.
It is an immunosuppressant drug combined with drugs such as Cyclosporine.
They are specific 5-HT and various degrees NE reuptake inhibition.
Venlafaxine, at lower doses (75–100 mg/day) acts as SSRI. As the dose increases it inhibit NE reuptake (& 2ry ↓ DA reuptake in prefrontal cortex, which lacks DAT→ ↑ DA).
This presentation was delivered over two days to second year pharmacy students enrolled in a course in pharmacology & toxicology. This lecture is designed to accompany Goodman & Gilman's (12e) chapter 11.
nitrates mechanism of action,overview of nitroglycerin[short acting], iso sorbide dinitrates, iso sorbide mononitrates, amyl nitrates and nitroprusside,
There are two distinct goals of drug therapy in CHF.
Relief of congestion/ low cardiac output symptoms and restoration of cardiac performance.
Ionotropic agents, Vasodilators, Diuretics, BETA Blockers.
Arrest/reversal of disease progression and prolongation of survival.
ACE inhibitors, ARBs, Beta Blockers, Aldosterone Antagonists.
Please find the power point on Choice of Antiepileptic drugs. I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Hypolipidemic agents, also known as cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are also called lipid-lowering drugs.
nitrates mechanism of action,overview of nitroglycerin[short acting], iso sorbide dinitrates, iso sorbide mononitrates, amyl nitrates and nitroprusside,
There are two distinct goals of drug therapy in CHF.
Relief of congestion/ low cardiac output symptoms and restoration of cardiac performance.
Ionotropic agents, Vasodilators, Diuretics, BETA Blockers.
Arrest/reversal of disease progression and prolongation of survival.
ACE inhibitors, ARBs, Beta Blockers, Aldosterone Antagonists.
Please find the power point on Choice of Antiepileptic drugs. I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Hypolipidemic agents, also known as cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are also called lipid-lowering drugs.
IVMS is the ultimate medical student Web 2.0 companion. This SDL-Face to Face hybrid courseware is a digitally tagged and content enhanced replication of the United States Medical Licensing Examination's Cognitive Learning Objectives (Steps 1, 2 or 3). Including authoritative reusable learning object (RLO) integration and scholarly Web Interactive PowerPoint-driven multimedia shows/ PDFs. Comprehensive hypermedia BMS learning outcomes and detailed, content enriched learning objectives.
Congestive Heart FailureAbstractThe primary function of the he.docxmaxinesmith73660
Congestive Heart Failure
Abstract
The primary function of the heart is to pump blood to all organs of the body, delivering oxygen and nutrients to the tissues and at the same removing waste products. At rest, organs need a certain amount of blood for this function. During activity, there are greater demands on the heart and more blood perfusion is required. To meet this varying demands, the heart rate and force of contraction of the heart may change and the blood vessels vasodilate to deliver more blood to the organs. In an individual with congestive heart failure (CHF), the heart is not able to meet these demands or is not able to work efficiently as it should. There are many causes of CHF some of which are reversible. However, heart failure can be sudden and present with a variety of symptoms such as dyspnea. Over time the architecture of the heart changes as it enlarges-this also alters the geometry of the valves leading to mitral valve regurgitation which makes heart failure worse. Overall, the prognosis of patients with heart failure is guarded and they have a poor quality of life.
Introduction
Heart failure is a pathological medical disorder where there is an abnormality of heart function, which results in an inability to pump blood to the rest of the body resulting in poor perfusion of the organs (Dumitru & Ooi, 2015). Heart failure may be due to systolic dysfunction where the pumping action of the hart is reduced or it may be diastolic where the heart chambers do not fill adequately because of stiffness in the walls. The clinical signs of heart failure depend on whether there is right or left heart failure. Heart failure is classified by the New York Heart Association based on presence of symptoms and the degree of effort needed to trigger them as follows:
· Class I patients have no limitation of physical activity
· Class II patients have slight limitation of physical activity
· Class III patients have marked limitation of physical activity
· Class IV patients have symptoms even at rest and are unable to carry on any physical activity without discomfort
Pathophysiology
The pathophysiology of heart failure is complex because of presence of compensatory mechanisms at all levels of the organization of the heart and other systemic influences. It is only when these network of organizations become overwhelmed that heart failure occurs. In summary the inefficient heart pumping results in back-up of fluids to lungs (Left sided failure) or peripheral tissues (Right sided failure). Compensatory mechanisms that occur include changes in myocyte size (ie hypertrophy) and activation of various neurohumoral systems. There is release of catecholamines by the sympathetic nerves to enhance myocardial contractility, activation of the activation of the renin-angiotensin-aldosterone system and other vasoregulating adjustments to maintain mean arterial pressure and perfusion of vital organs (Urso et al, 2015).
Etiology
The majority of patients who present.
Role of Clinical Pharmacist in Management of Congestive Heart Failure – A Bri...BRNSS Publication Hub
Heart failure (HF) is a clinical condition occurs when cardiac output is insufficient to meet the demands of tissue perfusion or does so by elevating filling pressure. HF is due to either systolic or diastolic dysfunction which reduces ventricular filling (diastolic dysfunction) and/or myocardial contractility (systolic dysfunction). Clinically, cardiac disease prevalence increases with individual age. Cardiac dysfunction occurs due to change in blood volume, and neurohumoral transmission status these desirable mechanisms to maintain adequate cardiac output and arterial blood pressure. The activation of three compensatory neurohormonal systems triggers the cardiac dysfunction leads to HF. Clinical pharmacist plays a role in disease management by identifying the risk factors, stage of severity, educating the patients and health-care practitioners and implementing the awareness programs, and modification of lifestyle interventions with in health-care system beneficial to the community may reduce the progression of disease severity.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Pharmacology- Management of Heart Failure- w Updates
1. CV Pharmacology
Pharmacological Management of
Congestive Heart Failure
Prepared and Presented by:
Marc Imhotep Cray, M.D.
BMS & CK Teacher
Companion Reading (Notes):
Pharmacological Treatment of
Heart Failure (Klabunde)
Drugs Acting on the
Cardiovascular System (Cray)
Formative Assessment
Cardiovascular Pharmacology
Review Test
Clinical:
e-Medicine article
Congestive Heart Failure and
Pulmonary Edema
http://www.emedicine.com/emerg/TOPIC108.HTM
2. 2
Learning Objectives:
1. Understand the underlying hemodynamic
abnormalities in heart failure and the therapeutic
approaches to its treatment
2. Understand the properties of angiotensin
converting enzyme inhibitors, angiotensin II
receptor blockers and vasodilators used to treat
heart failure and the rationale behind their use
3. Understand the properties of intravenous agents
(dobutamine, dopamine and PDE inhibitors) used in
the treatment of heart failure
4. Understand the actions of beta blockers and the
rationale for their use in the treatment of heart
failure
5. Know the pharmacologic action, toxicities and uses
of cardiac glycosides
By the end of this presentation the
learner should:
3. 3
Definition of HF
Chronic heart failure (HF) is an imbalance in
pump function in which heart fails to
adequately maintain circulation of blood.
The most severe manifestation of HF,
pulmonary edema, develops when this
imbalance causes an increase in lung fluid
secondary to leakage from pulmonary capillaries
into the interstitium and alveoli of the lung…
See cloud e-Medicine Article
Congestive Heart Failure and Pulmonary Edema
4. 4
Classification of HF
1. The side of the heart involved, (left heart
failure versus right heart failure)
2. Whether the abnormality is due to
contraction or relaxation of the heart
(Systolic Dysfunction vs. Diastolic
Dysfunction )
3. Whether the problem is primarily increased
venous back pressure (behind) the heart,
or failure to supply adequate arterial
perfusion (in front of) the heart
(backward vs. forward failure)
4. Whether the abnormality is due to low
cardiac output with high systemic vascular
resistance or high cardiac output with low
vascular resistance (low-output heart
failure vs. high-output heart failure)
5. The degree of functional impairment
conferred by the abnormality (as in the
NYHA functional classification)
There are many different ways to
categorize heart failure, including:
6. 6
Congestive Heart Failure:
Causes (cont.)
1. Arrhythmias: In patients with heart disease and with a
history of congestive failure, an acute arrhythmia is a
common precipitating cause of HF
Tachyarrhythmias decrease filling time and as a result
decrease cardiac output
A-V dissociation results in loss of the atrial contribution to
ventricular filling.
end-diastolic volume is reduced with an attendant reduction in
cardiac output
Abnormal intraventricular conduction may cause a reduced
synchronicity of contraction with a reduction in myocardial
performance
Severe bradycardia in the absence of increased stroke
volume can seriously reduce cardiac output and thus precipitate
HF
Increased stroke volume may not be possible if the patient has
significant heart disease
7. 7
Congestive Heart Failure:
Causes (cont.)
2. Myocardial Infarction: A myocardial infarction, reducing left
ventricular function, may precipitate HF in a previously
hemodynamically compensated patient
3. Pulmonary Embolism: Physically inactive patients with low
cardiac output may develop deep venous thrombi which may produce
pulmonary emboli and elevation of pulmonary arterial pressure
• Increased pulmonary artery pressure may worsen or cause left
ventricular failure
4. Systemic Hypertension: Rapid increases in arterial blood
pressure with associated increases in peripheral resistance can increase
afterload to an extent sufficient to produce heart failure.
8. Congestive Heart Failure:
Causes (cont.)
8
5. Other causes:
• Thyrotoxicosis
• Pregnancy
• Infection
• Anemia
• Rheumatic and other
forms of Myocarditis
• Physical, dietary, fluid
• Environmental and
emotional excesses
• Infective Endocarditis
9. 9
Pathophysiology in HF
HF is summarized best
as an imbalance in
Starling forces or an
imbalance in the
degree of end-diastolic
fiber stretch
proportional to the
systolic mechanical
work expended in an
ensuing contraction.
http://www.cvpharmacology.com/clinical topics/heart failure-2.htm
Cardiac and Vascular
Changes Accompanying
Heart Failure
Cardiac
Decreased SV and CO
Increased end-diastolic
pressure
Vascular
Increased SVR
Decreased arterial pressure
Decreased venous compliance
Increased venous pressure
Increased blood volume
10. Pathophysiology in HF(2)
10
Compensatory Mechanisms During Heart Failure
Cardiac
Frank-Starling mechanism
Ventricular dilation or hypertrophy
Tachycardia
Autonomic Nerves
Increased sympathetic adrenergic activity
Reduced vagal activity to heart
Hormones
Renin-angiotensin-aldosterone system (RAAS)
Vasopressin (antidiuretic hormone/ADH)
Circulating catecholamines
Natriuretic peptides
11. 11
Pathophysiology in HF (2)
The fundamental abnormality in
heart failure is embodied in:
depression of the myocardial
force-velocity relationship and
length-active tension curves that
result in impairment of
myocardial contractility (see
Figure, right)
When a normal heart transitions
from the resting state (1) to exercise
(2) a significant increase in
ventricular performance occurs.
By contrast in the failing heart, the
exercise-induced increases in
ventricular performance are minimal
(3' to 3).
From: http://www.pharmacology2000.com/Cardio/HF/HFobj1.htm
13. Physiologic Effects of AII
13
N.B.The RAAS is modulated by natriuretic peptides (ANP and
BNP) released by the heart. These natriuretic peptides acts as
an important counter-regulatory system
Constricts resistance vessels (via AII [AT1] receptors) thereby
increasing systemic vascular resistance and arterial pressure
Stimulates sodium transport (reabsorption) at several renal tubular
sites, thereby increasing sodium and water retention
Acts on adrenal cortex to release aldosterone, which in turn acts on
kidneys to increase sodium and fluid retention
Stimulates release of vasopressin (antidiuretic hormone, ADH) from
the posterior pituitary, which increases fluid retention by kidneys
Stimulates thirst centers within the brain
Facilitates norepinephrine release from sympathetic nerve endings
and inhibits norepinephrine re-uptake by nerve endings, thereby
enhancing sympathetic adrenergic function
Stimulates cardiac hypertrophy and vascular hypertrophy
15. Clinical Perspective and
Considerations
15
Heart failure, inability of circulatory system to meet
metabolic demands of body, is a multifaceted “disease
state” (syndrome) involving several organ systems
and neurohumoral factors including heart, kidney,
vascular system and brain
There are several forms of heart failure with multiple
etiologies
The treatment of heart failure is a particularly
difficult therapeutic problem with no single drug or
drug class adequate to provide complete relief from
the signs and symptoms of the syndrome
16. Clinical Perspective and
Considerations (2)
16
The drugs used and their specific therapeutic
approaches depend on underlying pathophysiology and
severity of the disease
While drug therapy is capable of symptomatic relief, it
does not correct the underlying pathology
Regardless of treatment, 50 % of individuals die within
5 years of developing HF.
In an era where morbidity and mortality from other
cardiovascular diseases are decreasing, deaths from HF
are increasing
17. Framingham Criteria for
Congestive Heart Failure
17
Diagnosis of HF requires the simultaneous presence of at
least 2 major criteria or 1 major criterion in conjunction with
2 minor criteria.
Major criteria:
•Paroxysmal nocturnal dyspnea
•Neck vein distention
•Rales
•Radiographic cardiomegaly (increasing heart size on chest
radiography)
•Acute pulmonary edema
•S3 gallop
•Increased central venous pressure (>16 cm H2O at right
atrium)
•Hepatojugular reflux
•Weight loss >4.5 kg in 5 days in response to treatment
18. Framingham Criteria for
Congestive Heart Failure (2)
18
Minor criteria:
•Bilateral ankle edema
•Nocturnal cough
•Dyspnea on ordinary exertion
•Hepatomegaly
•Pleural effusion
•Decrease in vital capacity by one third from maximum
recorded
•Tachycardia (heart rate>120 beats/min.)
N.B. Minor criteria are acceptable only if they can not be
attributed to another medical condition (such as
pulmonary hypertension, chronic lung disease, cirrhosis,
ascites, or nephrotic syndrome)
http://www.fpnotebook.com/CV/Exam/FrmnghmHrtFlrDgnstcCrtr.htm
19. 19
New York Heart Association (NYHA)
Functional Classification
The New York Heart Association (NYHA)
Functional Classification provides a simple
way of classifying the extent of heart failure
It places patients in one of four categories
based on how much they are limited during
physical activity
limitations/symptoms are in regards to
normal breathing and varying degrees in
shortness of breath and or angina pain
http://www.fpnotebook.com/CV/Exam/FrmnghmHrtFlrDgnstcCrtr.htm
20. 20
New York Heart Association (NYHA)
Functional Classification (2)
NYHA Class Symptoms
I
No symptoms and no limitation in ordinary physical
activity, e.g. shortness of breath when walking,
climbing stairs etc.
II
mild symptoms (mild shortness of breath and/or
angina) and slight limitation during ordinary activity.
III
Marked limitation in activity due to symptoms,
even during less-than-ordinary activity, e.g. walking
short distances (20-100 m). Comfortable only at rest.
IV
Severe limitations. Experiences symptoms even
while at rest. Mostly bedbound patients.
Source: http://www.medicalcriteria.com/criteria/nyha.htm
21. 21
Rationale for Drug Therapy (Clickable)
The primary goal of drug
therapy in heart failure is
to improve cardiac function
and reduce the clinical
symptoms associated with
heart failure (e.g., edema,
shortness of breath,
exercise intolerance). B D= Vasodilator Effect
B E= Inotropic Effect
22. DRUGS AND DRUG CLASSES USED
TO TREAT HEART FAILURE
(See last slide for complete list)
22
1. Vasodilators - Drugs that decrease either preload or
afterload
ACE inhibitors, AT1 blockers, and other vasodilators and
diuretics
a) Arterial selective vasodilators decrease PVR and afterload
on the failing myocardium
reduction in afterload leads to an increased CO and improved tissue
perfusion
b) Venous selective vasodilators increase venous capacitance,
thus decreasing preload
A small reduction in venous tone can result in a pooling of large amounts
of blood
This would decrease left ventricular filling pressure and pulmonary
congestion
23. DRUGS AND DRUG CLASSES USED
TO TREAT HEART FAILURE (2)
23
c) The major vasodilators used are ACE inhibitors and
angiotensin II receptor antagonists (ARBs)
d) Other agents include organic nitrates, hydralazine and
nitroprusside ( all 3 reduce both preload & afterload)
e) In addition, diuretics promote the elimination of
edematous fluid, improving tissue perfusion and
pulmonary function
N.B. Chronic thiazide diuretic Tx also results in relaxation
of resistance vessels)
24. DRUGS AND DRUG CLASSES USED
TO TREAT HEART FAILURE (3)
24
2. Positive Inotropic Agents Drugs that increase
contractile force; beta1 receptor agonists, cAMP PDE
inhibitors, cardiac glycosides
3. Beta blockers (not acute HF, but decrease mortality in
chronic HF)
4. Diuretics Cornerstone drugs in the treatment of heart
failure. Noteworthy are loop diuretics and aldosterone
receptor antagonists.
N.B. In addition to effects on circulatory system, some of
these agents also block the cellular responses that lead to
cardiac remodeling and hypertrophy
25. 25
Overview of HF Pharmacological
Management
Treatment of HF aims
to relieve symptoms,
to maintain a euvolemic state (normal fluid
level in the circulatory system), and
to improve prognosis by delaying
progression of heart failure and reducing
cardiovascular risk
27. 27
Overview of HF Pharmacological
Management (3)
Angiotensin-modulating agents
ACE inhibitor (ACE) therapy is recommended
for all patients with systolic heart failure,
irrespective of symptomatic severity or blood
pressure
ACE inhibitors improve symptoms, decrease mortality
and reduce ventricular hypertrophy
Angiotensin II receptor antagonist therapy
(also referred to as AT1-antagonists or
angiotensin receptor blockers/ARBs), particularly
using candesartan, is an acceptable alternative
if the patient is unable to tolerate ACEI therapy
28. 28
Overview of HF Pharmacological
Management(4)
Angiotensin-modulating agents cont.
ACEIs and ARBs decrease afterload by
antagonizing the vasopressor effect of
angiotensin, thereby decreasing the amount of
work the heart must perform
It is also believed that angiotensin directly
affects cardiac remodeling, and blocking its
activity can thereby slow deterioration of
cardiac function
30. Overview of HF Pharmacological
Management (5)
30
Many ACE inhibitors have been developed
Captopril was the first agent developed and hence is the
prototype
Enalapril is a prodrug that is de-esterified by plasma esterases
to enalaprilat
Most of the ACEIs are activated in this fashion
Benazepril - Metabolized to benazeprilat
Captopril
Enalapril - Metabolized to enalaprilat
Fosinopril - Metabolized to fosinoprilat
Lisinopril
Moexipril- Metabolized to moexiprilat
Quinapril - Metabolized to quinaprilat
Ramipril - Metabolized to ramiprilat
Trandolapril-Metabolized to tandolaprilat
Perindopril - metabolized to perindoprilat
31. 31
Overview of HF Pharmacological
Management (6)
Commonly used Angiotensin Converting Enzyme (ACE) Inhibitors
32. 32
Overview of HF Pharmacological
Management(7)
MOA of Angiotensin Converting Enzyme (ACE) Inhibitors
33. 33
Overview of HF Pharmacological
Management (8)
Diuretics
Diuretic therapy is indicated for relief of congestive
symptoms. Several classes are used, with
combinations reserved for severe heart failure
Loop diuretics (e.g. furosemide, bumetanide) –
most commonly used class in HF, usually for
moderate HF
Thiazide diuretics (e.g. hydrochlorothiazide,
chlorthalidone, chlorthiazide) – may be useful for
mild HF, but typically used in severe HF in
combination with loop diuretics, resulting in a
synergistic effect
34. 34
Overview of HF Pharmacological
Management (9)
Diuretics cont.
Potassium-sparing diuretics (e.g.
amiloride) – used first-line use to correct
hypokalaemia.
Spironolactone is used as add-on therapy
to ACEI plus loop diuretic in severe HF
Eplerenone (Inspra®) is specifically
indicated for post-MI reduction of
cardiovascular risk
35. 35
Overview of HF Pharmacological
Management (10)
Beta blockers
Until recently (within the last 20 years), β-
blockers were contraindicated in HF, owing to
their negative inotropic effect and ability to
produce bradycardia – effects which worsen
heart failure
However, current guidelines recommend β-
blocker therapy for patients with systolic heart
failure due to left ventricular systolic dysfunction
after stabilization with diuretic and ACEI therapy,
irrespective of symptomatic severity or blood
pressure
36. 36
Overview of HF Pharmacological
Management (11)
Beta blockers cont.
As with ACEI therapy, the addition of a β-blocker can
decrease mortality and improve left ventricular function
Several β-blockers are specifically indicated for HF
including:
1. bisoprolol,
2. carvedilol, and
3. extended-release metoprolol
antagonism of β1 inotropic and chronotropic effects decreases
the amount of work the heart must perform
37. 37
Overview of HF Pharmacological
Management (12)
Beta blockers cont.
It is also thought that catecholamines and
other sympathomimetics have an effect
on cardiac remodeling, and blocking their
activity can slow the deterioration of
cardiac function
See: The Importance of Beta Blockers in the Treatment of Heart Failure
American Academy of Family Physicians
38. Overview of HF Pharmacological
Management (13)
38
CARDIAC GLYCOSIDES (Digitalis )
(Some history)
Cardiac glycosides are one of the oldest
groups of drugs used in cardiovascular
therapeutics
There is evidence of use in Egyptian and
Roman times
William Withering published medical accounts
of use of the "foxglove" for the treatment of
"dropsy."
Originally, extracts of d. purpurea were used
Two active principals, digoxin and digitoxin,
are now used in cardiovascular therapeutics
The uses of these drugs are in heart failure
and supraventricular tachyarrhythmias.
These agents have a low therapeutic index
Digitalis purpurea
(Common Foxglove)
39. 39
Overview of HF Pharmacological
Management (14)
Positive inotropes
Digoxin / Cardiac glycosides (a mildly positive inotrope
and negative chronotrope), once used as first-line therapy,
is now reserved for control of ventricular rhythm in
patients with atrial fibrillation; or where adequate control is
not achieved with an ACEI, a beta blocker and a loop
diuretic
There is no evidence that digoxin reduces mortality in HF,
although some studies suggest a decreased rate in hospital
admissions
It is contraindicated in cardiac tamponade and restrictive
cardiomyopathy
N.B. Cardiac glycosides not first line Tx for HF due to risk of toxicities
40. 40
Overview of HF Pharmacological
Management(15) Cardiac glycosides
Mechanism of Positive
Inotropic Action
Cardiac glycosides inhibit the
myocardial cell Na+, K+, ATPase
This enzyme is responsible for
maintaining ionic gradient of
myocardial cell.
Inhibition of the Na+, K+,
ATPase results in an increase in
intracellular Na+. Decrease in
Na+ gradient diminishes
exchange of Na+ for Ca2+
Increase in intracellular Ca2+ is
responsible for the positive
inotropic action
http://cvpharmacology.com/cardiostimulatory/digitalis.htm
41. 41
Antiarrhythmic Actions
Cardiac glycosides also work in the carotid arch and
baroreceptors to increase the sensitivity of these sites
results enhanced neural traffic to CNS
cardiovascular centers resulting in enhanced vagal outflow
to the myocardium
At the SA node this increase in vagal tone:
1. Increases SA nodal refractory period
2. Slows SA nodal conduction velocity
At the AV node (major site of antiarrhythmic action)
the increase in vagal tone:
1. Increases AV nodal refractory period
2. Slows AV nodal conduction velocity
Overview of HF Pharmacological
Management(15) Cardiac glycosides
42. 42
Pharmacokinetics of Cardiac Glycosides
AGENT
GASTRO
INTESTINAL
ABSORPTION
ONSET
OF
ACTION
(MIN)
PEAK
EFFECT
(HR)
AVERAG
E HALF
LIFE
PRINCIPAL
METABOLIC
ROUTE
(EXCRETORY
PATHWAY)
AVERAGE
DIGITALIZING
DOSES
USUAL
DAILY ORAL
MAINTENAN
CE DOSESoral IV
Digoxin 30 to 100% 15 to 30 1 1/2 to 5
36 to 48
hours
Renal; some
gastrointestinal
excretion
1.25 to
1.5 mg
0.75 to
1.00 mg
0.25 to 0.5 mg
Digitoxin 90 to 100% 25 to 120 4 to 12
4 to 6
days
Hepatic; renal
excretion of
metabolites
0.7 to
1.2 mg
1.00 mg 0.1 mg
Special Considerations / Next Slide
Overview of HF Pharmacological
Management(16) Cardiac glycosides
43. Special Considerations
43
Factors that can alter the therapeutic response
to cardiac glycosides:
Renal disease decreased renal clearance of digoxin
Drug Interactions that:
a) Decrease bioavailability Cholestyramine
b) Decrease renal clearance Amiodarone ,Verapamil ,
Quinidine
Hypokalemia and Electrolytes
Hypokalemia increases the likelihood of toxicity
Alterations in potassium levels could be exacerbated
by co-administration of diuretics
Age elderly are more sensitive to cardiac glycosides
Hypoxia increases the likelihood of toxicity
44. 44
Positive inotropes cont.
The inotropic agent dobutamine is advised only in the
short-term use of acutely decompensated heart failure,
and has no other uses (Bata1 receptor agonist)
Phosphodiesterase inhibitors such as milrinone are
sometimes utilized in severe cardiomyopathy (increase
cAMP/See phosphodiesterase inhibitors )
The mechanism of action is through antagonism of
adenosine receptors, resulting in inotropic effects and
modest diuretic effects
Overview of HF Pharmacological
Management(17)
45. 45
Alternative vasodilators
The combination of isosorbide dinitrate/hydralazine is the
only vasodilator regimen, other than ACE inhibitors or
angiotensin II receptor antagonists, with proven survival
benefits
This combination appears to be particularly beneficial in
HF patients with an African American background, who
respond less effectively to ACEI therapy
See next slide
Overview of HF Pharmacological
Management (18)
46. Overview of HF Pharmacological
Management (19)
46
Exner DV, Dries DL, Domanski MJ, Cohn JN (2001). "Lesser
response to angiotensin-converting-enzyme inhibitor therapy
in black as compared with white patients with left ventricular
dysfunction". N Engl J Med. 344 (18): 1351–7.
doi:10.1056/NEJM200105033441802.
Taylor AL, etal; (2004). African-American Heart Failure Trial
Investigators. "Combination of isosorbide dinitrate and
hydralazine in blacks with heart failure". N Engl J Med 351
(20): 2049–57. doi:10.1056/NEJMoa042934.
47. 47From: Medical Pharmacology at a Glance, 7th Ed. Michael J. Neal. 2012 John Wiley & Sons, Ltd: Pg. 49
Drugs Used in Heart Failure:
Schematic Summary
49. Recommended links and resource
for further study:
Cardiovascular Physiology
Concepts, 2nd edition,
LLW (2011)
Diuretics
- thiazide diuretics
- loop diuretics
- natriuretic peptides
Vasodilators (dilate arteries and veins)
- angiotensin converting enzyme (ACE) inhibitors
- angiotensin receptor blockers (ARBs)
- direct acting arterial dilators
- nitrodilators
- natriuretic peptides
- phosphodiesterase inhibitors
Cardiostimulatory or inotropic drugs (stimulate contractility)
- digitalis
- beta-agonists (sympathomimetic drugs)
- phosphodiesterase inhibitors
Cardioinhibitory
- beta-blockers
- calcium-channel blockers (for diastolic dysfunction)
Classes of drugs used in the treatment of heart failure by Richard E.
Klabunde, PhD are given below. Clicking on the drug class will link
you to the page describing the pharmacology of that drug class.