This document provides an overview of asthma, including its pathophysiology, clinical presentation, diagnosis, and treatment. It defines asthma as a chronic inflammatory disorder of the airways characterized by variable airflow obstruction and bronchial hyperresponsiveness. The pathophysiology involves activation of mast cells and macrophages by inhaled allergens, leading to airway inflammation and constriction. Clinical presentations range from mild intermittent symptoms to severe acute exacerbations. Diagnosis is based on symptoms and spirometry showing reversible airflow obstruction. Treatment involves patient education, environmental control, pharmacotherapy including short-acting beta-agonists, and management of acute exacerbations with supplemental oxygen and hydration.
Bronchial Asthma: Definition,Pathophysiology and ManagementMarko Makram
Definition and Pathophysiology of Asthma in addition to classification and recent updates in the management of asthma based on GINA-2019 Guidelines, by Dr. Marco Makram.
BRONCHIAL ASTHMA
ntroduction
Definition
Etiological factors
Pathophysiology
Types of asthma
Clinical manifestation Restlessness Wheezing or crackles Absent or diminished lung sounds Hyper resonance Use of accessory muscles for breathing Tachypnea with hyperventilation
Clinical manifestation
Diagnostic evaluation
Bronchoprovocation Testing: Testing that is done to identify inhaled allergens; mucous membranes are directly exposed to suspected allergen in increasing amounts. Skin Testing: Done to identify specific allergens. Exercise Challenges: Exercise is used to identify the occurrence of exercise-induced bronchospasm. Radio allergosorbent Test: Blood test used to identify a specific allergen. Chest Radiograph: May show hyper expansion of the airways.
Managemnet
Goal- Promote bronchodilationn Reduce inflammation Remove secretions Prevent ongoing symptoms Prevent asthma attack Maintain normal lung function Avoid triggers
Pharmacological therapy 1. Long term control medication- Inhaled corticosteroid Leukotriene modifiers Long acting beta agonist Methylxanthines Combine inhaler
2 Quick relief medication Short acting beta agonist Anticholinergic Oral or I/V corticosteroid
3 Bronchial thermoplasty- Form severe asthma that does not respond to medication
Non- pharmacological
Oxygen therapy Postural drainage & chest physiotherapy Coughing & deep breathing exercise Avoidance of allergen relaxation technique acupuncture
Prevention
Patients with recurrent asthma should undergo tests to identify the substances that precipitate the symptoms. Possible causes are dust, dust mites, roaches, certain types of cloth, pets, horses, detergents, soaps, certain foods, molds, and pol- lens. If the attacks are seasonal, pollens can be strongly sus- pected. Patients are instructed to avoid the causative agents whenever possible.
Complications Complications of asthma may include status asthmaticus, respiratory failure, pneumonia, and atelectasis. Airway obstruction, particularly during acute asthmatic episodes, often results in hypoxemia, requiring the administration of oxygen and the monitoring of pulse oximetry and arterial blood gases. Fluids are administered, because people with asthma are frequently dehydrated from diaphoresis and in- sensible fluid loss with hyperventilation.
Nursing diagnosis
Impaired gas exchange r/t altered oxygen supply Ineffective airway clearance r/t bronchospasm & obstruction from narrow lumen Ineffective breathing pattern r/t bronchospasm Risk for increasing attack of r
espiratory distress r/t exposure to allergens
“Asthma is a chronic inflammatory disorder of the airways causing airflow obstruction and recurrent episodes of wheezing, breathlessness, chest tightness, and coughing ”.
There is a variable degree of airflow obstruction (related to bronchospasm, edema, and hypersecretion), bronchial hyperresponsiveness (BHR), and airway inflammation.
Bronchial Asthma: Definition,Pathophysiology and ManagementMarko Makram
Definition and Pathophysiology of Asthma in addition to classification and recent updates in the management of asthma based on GINA-2019 Guidelines, by Dr. Marco Makram.
BRONCHIAL ASTHMA
ntroduction
Definition
Etiological factors
Pathophysiology
Types of asthma
Clinical manifestation Restlessness Wheezing or crackles Absent or diminished lung sounds Hyper resonance Use of accessory muscles for breathing Tachypnea with hyperventilation
Clinical manifestation
Diagnostic evaluation
Bronchoprovocation Testing: Testing that is done to identify inhaled allergens; mucous membranes are directly exposed to suspected allergen in increasing amounts. Skin Testing: Done to identify specific allergens. Exercise Challenges: Exercise is used to identify the occurrence of exercise-induced bronchospasm. Radio allergosorbent Test: Blood test used to identify a specific allergen. Chest Radiograph: May show hyper expansion of the airways.
Managemnet
Goal- Promote bronchodilationn Reduce inflammation Remove secretions Prevent ongoing symptoms Prevent asthma attack Maintain normal lung function Avoid triggers
Pharmacological therapy 1. Long term control medication- Inhaled corticosteroid Leukotriene modifiers Long acting beta agonist Methylxanthines Combine inhaler
2 Quick relief medication Short acting beta agonist Anticholinergic Oral or I/V corticosteroid
3 Bronchial thermoplasty- Form severe asthma that does not respond to medication
Non- pharmacological
Oxygen therapy Postural drainage & chest physiotherapy Coughing & deep breathing exercise Avoidance of allergen relaxation technique acupuncture
Prevention
Patients with recurrent asthma should undergo tests to identify the substances that precipitate the symptoms. Possible causes are dust, dust mites, roaches, certain types of cloth, pets, horses, detergents, soaps, certain foods, molds, and pol- lens. If the attacks are seasonal, pollens can be strongly sus- pected. Patients are instructed to avoid the causative agents whenever possible.
Complications Complications of asthma may include status asthmaticus, respiratory failure, pneumonia, and atelectasis. Airway obstruction, particularly during acute asthmatic episodes, often results in hypoxemia, requiring the administration of oxygen and the monitoring of pulse oximetry and arterial blood gases. Fluids are administered, because people with asthma are frequently dehydrated from diaphoresis and in- sensible fluid loss with hyperventilation.
Nursing diagnosis
Impaired gas exchange r/t altered oxygen supply Ineffective airway clearance r/t bronchospasm & obstruction from narrow lumen Ineffective breathing pattern r/t bronchospasm Risk for increasing attack of r
espiratory distress r/t exposure to allergens
“Asthma is a chronic inflammatory disorder of the airways causing airflow obstruction and recurrent episodes of wheezing, breathlessness, chest tightness, and coughing ”.
There is a variable degree of airflow obstruction (related to bronchospasm, edema, and hypersecretion), bronchial hyperresponsiveness (BHR), and airway inflammation.
Etiopathogenesis and pharmacotherapy of Asthma
the pathophysiology of selected disease states and the rationale for drug therapy;
b. the therapeutic approach to management of these diseases;
c. the controversies in drug therapy;
d. the importance of preparation of individualised therapeutic plans based on diagnosis;
e. needs to identify the patient-specific parameters relevant in initiating drug therapy,
and monitoring therapy (including alternatives, time-course of clinical and laboratory
indices of therapeutic response and adverse effects);
f. describe the pathophysiology of selected disease states and explain the rationale for
drug therapy;
g. summarise the therapeutic approach to management of these diseases including
reference to the latest available evidence;
h. discuss the controversies in drug therapy;
i. discuss the preparation of individualised therapeutic plans based on diagnosis; and
j. identify the patient-specific parameters relevant in initiating drug therapy, and
monitoring therapy (including alternatives, time-course of clinical and laboratory indices of therapeutic response and adverse effects).
Asthma is a chronic respiratory condition characterized by inflammation and narrowing of the airways, leading to symptoms like wheezing, coughing, shortness of breath, and chest tightness. It can be triggered by various factors including allergens, respiratory infections, exercise, smoke, and pollutants. Management involves medication, identifying triggers, creating an action plan, monitoring symptoms, staying active, maintaining a healthy lifestyle, getting vaccinated, and regular check-ups with healthcare providers. Effective management aims to control symptoms, prevent flare-ups, and improve overall quality of life.
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
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
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.
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.
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2. INTRODUCTION
• The National Asthma Education and Prevention Program (NAEPP) defines
asthma as a chronic inflammatory disorder of the airways in which many
cells and cellular elements play a role.
• In susceptible individuals, inflammation causes recurrent episodes of
wheezing, breathlessness, chest tightness, and coughing.
• These episodes are usually associated with airflow obstruction that is
often reversible either spontaneously or with treatment.
• The inflammation also causes an increase in bronchial hyper
responsiveness (BHR) to a variety of stimuli.
3 September 2015 2
3. PATHOPHYSIOLOGY
• The major characteristics of asthma include a variable degree of airflow
obstruction (related to bronchospasm, edema, and hypersecretion), BHR,
and airway inflammation.
• Inhaled allergens cause an early-phase allergic reaction characterized by
activation of cells bearing allergen-specific immunoglobulin E (IgE)
antibodies.
• There is rapid activation of airway mast cells and macrophages, which
release proinflammatory mediators such as histamine and eicosanoids
that induce contraction of airway smooth muscle, mucus secretion,
vasodilation, and exudation of plasma in the airways.
• Plasma protein leakage induces a thickened, engorged, edematous airway
wall and a narrowing of the airway lumen with reduced mucus clearance.
3 September 2015 3
4. • The late-phase inflammatory reaction occurs 6 to 9 hours after allergen
provocation and involves recruitment and activation of eosinophils, T
lymphocytes, basophils, neutrophils, and macrophages.
• Eosinophils migrate to the airways and release inflammatory mediators
(leukotrienes and granule proteins), cytotoxic mediators, and cytokines.
• T-lymphocyte activation leads to release of cytokines from type 2 T-helper
(TH2) cells that mediate allergic inflammation (interleukin [IL]-4, IL-5, and
IL-13).
• Conversely, type 1 T-helper (TH1) cells produce IL-2 and interferon- γ that
are essential for cellular defense mechanisms. Allergic asthmatic
inflammation may result from an imbalance between TH1 and TH2 cells.
3 September 2015 4
5. • Mast cell degranulation in response to allergens results in release of
mediators such as histamine; eosinophil, and neutrophil chemotactic
factors; leukotrienes C4, D4, and E4; prostaglandins; and platelet-
activating factor (PAF).
• Histamine is capable of inducing smooth muscle constriction and
bronchospasm and may play a role in mucosal edema and mucus
secretion.
• Alveolar macrophages release a number of inflammatory mediators,
including PAF and leukotrienes B4, C4, and D4. Production of neutrophil
chemotactic factor and eosinophil chemotactic factor furthers the
inflammatory process.
• Neutrophils are also a source of mediators (PAFs, prostaglandins,
thromboxanes, and leukotrienes) that contribute to BHR and airway
inflammation.
3 September 2015 5
6. • The 5-lipoxygenase pathway of arachidonic acid metabolism is responsible
for production of cysteinyl leukotrienes. Leukotrienes C4, D4, and E4 are
released during inflammatory processes in the lung and produce
bronchospasm, mucus secretion, microvascular permeability, and airway
edema.
• Bronchial epithelial cells participate in inflammation by releasing
eicosanoids, peptidases, matrix proteins, cytokines, and nitric oxide.
• Epithelial shedding results in heightened airway responsiveness, altered
permeability of the airway mucosa, depletion of epithelial-derived
relaxant factors, and loss of enzymes responsible for degrading
inflammatory neuropeptides.
• The exudative inflammatory process and sloughing of epithelial cells into
the airway lumen impair mucociliary transport. The bronchial glands are
increased in size, and the goblet cells are increased in size and number.
3 September 2015 6
7. • Expectorated mucus from patients with asthma tends to have high
viscosity. The airway is innervated by parasympathetic, sympathetic, and
nonadrenergic inhibitory nerves.
• The normal resting tone of airway smooth muscle is maintained by vagal
efferent activity, and bronchoconstriction can be mediated by vagal
stimulation in the small bronchi.
• Airway smooth muscle contains noninnervated β2-adrenergic receptors
that produce bronchodilation.
• The nonadrenergic, noncholinergic nervous system in the trachea and
bronchi may amplify inflammation in asthma by releasing nitric oxide.
3 September 2015 7
9. CHRONIC ASTHMA
• Classic asthma is characterized by episodic dyspnea associated with
wheezing, but the clinical presentation of asthma is diverse.
• Patients may also complain of episodes of dyspnea, chest tightness,
coughing (particularly at night), wheezing, or a whistling sound when
breathing. These often occur with exercise but may occur spontaneously
or in association with known allergens.
• Signs include expiratory wheezing on auscultation, dry hacking cough, or
signs of atopy (e.g., allergic rhinitis or eczema). Asthma can vary from
chronic daily symptoms to only intermittent symptoms.
3 September 2015 9
10. • The intervals between symptoms may be days, weeks, months, or years.
• The severity is determined by lung function, symptoms, nighttime
awakenings, and interference with normal activity prior to therapy.
• Patients can present with mild intermittent symptoms that require no
medications or only occasional use of short-acting inhaled β2-agonists to
severe chronic asthma symptoms despite receiving multiple medications.
3 September 2015 10
12. SEVERE ACUTE ASTHMA
• Uncontrolled asthma can progress to an acute state where inflammation,
airway edema, excessive mucus accumulation, and severe bronchospasm
result in profound airway narrowing that is poorly responsive to usual
bronchodilator therapy.
• Patients may be anxious in acute distress and complain of severe dyspnea,
shortness of breath, chest tightness, or burning. They may be able to say
only a few words with each breath. Symptoms are unresponsive to usual
measures.
• Signs include expiratory and inspiratory wheezing on auscultation, dry
hacking cough, tachypnea, tachycardia, pallor or cyanosis, and
hyperinflated chest with intercostal and supraclavicular retractions. Breath
sounds may be diminished with very severe obstruction.
3 September 2015 12
14. CHRONIC ASTHMA
• The diagnosis of asthma is made primarily by a history of recurrent
episodes of coughing, wheezing, chest tightness, or shortness of breath
and confirmatory spirometry.
• The patient may have a family history of allergy or asthma or have
symptoms of allergic rhinitis. A history of exercise or cold air precipitating
dyspnea or increased symptoms during specific allergen seasons also
suggests asthma.
• Spirometry demonstrates obstruction (forced expiratory volume in 1
second [FEV1]/forced vital capacity less than 80%) with reversibility after
inhaled β2-agonist administration (at least a 12% improvement in FEV1).
• Failure of pulmonary function to improve acutely does not necessarily rule
out asthma. If baseline spirometry is normal, challenge testing with
exercise, histamine, or methacholine can be used to elicit BHR.
3 September 2015 14
15. ACUTE SEVERE ASTHMA
• Peak expiratory flow (PEF) and FEV1 are less than 50% of normal predicted
values. Pulse oximetry reveals decreased arterial oxygen and O2 saturations.
The best predictor of outcome is early response to treatment as measured by
improvement in FEV1 at 30 minutes after inhale β2-agonists.
• Arterial blood gases may reveal metabolic acidosis and a low PaO2.
• The history and physical examination should be obtained while initial therapy
is being provided. A history of previous asthma exacerbations (e.g.,
hospitalizations, intubations) and complicating illnesses (e.g., cardiac disease,
diabetes) should be obtained.
• The patient should be examined to assess hydration status; use of accessory
muscles of respiration; and the presence of cyanosis, pneumonia,
pneumothorax, pneumomediastinum, and upper airway obstruction. A
complete blood count may be appropriate for patients with fever or purulent
sputum.
3 September 2015 15
17. NON PHARMACOLOGIC THERAPY
• Patient education and the teaching of self-management skills should be
the cornerstone of the treatment program. Self-management programs
improve adherence to medication regimens, self-management skills, and
use of healthcare services.
• Objective measurements of airflow obstruction with a home peak flow
meter may not necessarily improve patient outcomes. The NAEPP
advocates use of PEF monitoring only for patients with severe persistent
asthma who have difficulty perceiving airway obstruction.
• Avoidance of known allergenic triggers can improve symptoms, reduce
medication use, and decrease BHR. Environmental triggers (e.g., animals)
should be avoided in sensitive patients, and those who smoke should be
encouraged to stop.
3 September 2015 17
18. • Patients with acute severe asthma should receive supplemental oxygen
therapy to maintain arterial oxygen saturation above 90% (above 95% in
pregnant women and patients with heart disease).
• Significant dehydration should be corrected; urine specific gravity may
help guide therapy in young children, in whom assessment of hydration
status may be difficult.
3 September 2015 18
20. Β2-AGONISTS
• The short-acting β2-agonists are the most effective bronchodilators
available.
• β2-Adrenergic receptor stimulation activates adenyl cyclase, which
produces an increase in intracellular cyclic adenosine monophosphate.
• This results in smooth muscle relaxation, mast cell membrane
stabilization, and skeletal muscle stimulation.
3 September 2015 20
24. • Aerosol administration enhances bronchoselectivity and provides a more rapid
response and greater protection against provocations that induce
bronchospasm (e.g., exercise, allergen challenges) than does systemic
administration.
• Albuterol and other inhaled short-acting selective β 2 -agonists are indicated
for treatment of intermittent episodes of bronchospasm and are the first
treatment of choice for acute severe asthma and EIB. Regular treatment (four
times daily) does not improve symptom control over as-needed use.
• Formoterol and salmeterol are inhaled long-acting β 2 -agonists indicated as
adjunctive long-term control for patients with symptoms who are already on
low to medium doses of inhaled corticosteroids prior to advancing to medium-
or high-dose inhaled corticosteroids. Short-acting β 2 –agonists should be
continued for acute exacerbations. Long-acting agents are ineffective for acute
severe asthma because it can take up to 20 minutes for onset and 1 to 4 hours
for maximum bronchodilation after inhalation.
3 September 2015 24
25. • In acute severe asthma, continuous nebulization of short-acting β 2 –
agonists (e.g., albuterol) is recommended for patients having an
unsatisfactory response after three doses (every 20 minutes) of
aerosolized β 2 -agonists and potentially for patients presenting initially
with PEF or FEV 1 values <30% of predicted normal.
• Inhaled β 2 -agonists agents are the treatment of choice for EIB.
Shortacting agents provide complete protection for at least 2 hours after
inhalation; long-acting agents provide significant protection for 8 to 12
hours initially, but the duration decreases with chronic regular use.
3 September 2015 25
26. • In nocturnal asthma, long-acting inhaled β 2 -agonists are preferred over
oral sustained-release β 2 -agonists or sustained-release theophylline.
However, nocturnal asthma may be an indicator of inadequate
antiinflammatory treatment.
3 September 2015 26
27. CORTICOSTEROIDS
• Corticosteroids increase the number of β 2 -adrenergic receptors and
improve receptor responsiveness to β 2 -adrenergic stimulation, thereby
reducing mucus production and hypersecretion, reducing BHR, and
reducing airway edema and exudation.
• Inhaled corticosteroids are the preferred long-term control therapy for
persistent asthma in all patients because of their potency and consistent
effectiveness; they are also the only therapy shown to reduce the risk of
death from asthma.
• Most patients with moderate disease can be controlled with twice-daily
dosing; some products have once-daily dosing indications. Patients with
more severe disease require multiple daily dosing. Because the
inflammatory response of asthma inhibits steroid receptor binding,
patients should be started on higher and more frequent doses and then
tapered down once control has been achieved.
3 September 2015 27
28. • The response to inhaled corticosteroids is delayed; symptoms improve in
most patients within the first 1 to 2 weeks and reach maximum
improvement in 4 to 8 weeks. Maximum improvement in FEV1 and PEF
rates may require 3 to 6 weeks.
• Systemic toxicity of inhaled corticosteroids is minimal with low to
moderate inhaled doses, but the risk of systemic effects increases with
high doses. Local adverse effects include dose-dependent oropharyngeal
candidiasis and dysphonia, which can be reduced by the use of a spacer
device.
• The ability of spacer devices to enhance lung delivery is inconsistent and
should not be relied on.
3 September 2015 28
30. • Systemic corticosteroids are indicated in all patients with acute severe
asthma not responding completely to initial inhaled β2- agonist
administration (every 20 minutes for three to four doses).
• Prednisone, 1 to 2 mg/kg/day (up to 40 to 60 mg/day), is administered
orally in two divided doses for 3 to 10 days. Because short-term (1 to 2
weeks), high-dose systemic steroids do not produce serious toxicities, the
ideal method is to use a short burst and then maintain the patient on
appropriate long-term control therapy with inhaled corticosteroids.
• In patients who require chronic systemic corticosteroids for asthma
control, the lowest possible dose should be used. Toxicities may be
decreased by alternate-day therapy or high-dose inhaled corticosteroids.
3 September 2015 30
31. METHYLXANTHINES
• Theophylline appears to produce bronchodilation by inhibiting
phosphodiesterases, which may also result in antiinflammatory and other
nonbronchodilator activity through decreased mast cell mediator release,
decreased eosinophil basic protein release, decreased T-lymphocyte
proliferation, decreased T-cell cytokine release, and decreased plasma
exudation.
• Methylxanthines are ineffective by aerosol and must be taken systemically
(orally or IV). Sustained-release theophylline is the preferred oral
preparation, whereas its complex with ethylenediamine (aminophylline) is
the preferred parenteral product due to increased solubility. IV
theophylline is also available.
3 September 2015 31
32. • Theophylline is eliminated primarily by metabolism via hepatic
cytochrome P450 mixed-function oxidase microsomal enzymes (primarily
CYP1A2 and CYP3A4) with 10% or less excreted unchanged in the kidney.
• The hepatic cytochrome P450 enzymes are susceptible to induction and
inhibition by various environmental factors and drugs.
• The addition of theophylline to optimal inhaled corticosteroids is similar to
doubling the dose of the inhaled corticosteroid and is less effective overall
than the long-acting β2-agonists as adjunctive therapy.
3 September 2015 32
33. Anticholinergics
• Ipratropium bromide and tiotropium bromide are competitive inhibitors of
muscarinic receptors; they produce bronchodilation only in cholinergic
mediated bronchoconstriction. Anticholinergics are effective bronchodilators
but are not as potent as β2-agonists.
• The time to reach maximum bronchodilation from aerosolized ipratropium is
longer than from aerosolized short-acting β2-agonists (30 to 60 minutes vs. 5
to 10 minutes).
• This is of little clinical consequence because some bronchodilation is seen
within 30 seconds and 50% of maximum response occurs within 3 minutes.
• Ipratropium bromide has a duration of action of 4 to 8 hours; tiotropium
bromide has a duration of 24 hours.
3 September 2015 33
34. • Inhaled ipratropium bromide is only indicated as adjunctive therapy in
severe acute asthma not completely responsive to β2-agonists alone
because it does not improve outcomes in chronic asthma.
3 September 2015 34
35. Mast cell stabilizers
• Cromolyn sodium and nedocromil sodium have beneficial effects that are
believed to result from stabilization of mast cell membranes. They inhibit
the response to allergen challenge as well as EIB but do not cause
bronchodilation.
• These agents are effective only by inhalation and are available as metered
dose inhalers; cromolyn also comes as a nebulizer solution.
• Both drugs are remarkably nontoxic. Cough and wheezing have been
reported after inhalation of each agent, and bad taste and headache after
nedocromil.
3 September 2015 35
36. • Cromolyn and nedocromil are indicated for the prophylaxis of mild persistent
asthma in children and adults regardless of etiology. Their effectiveness is
comparable to theophylline or leukotriene antagonists for persistent asthma.
• Neither agent is as effective as inhaled corticosteroids for controlling persistent
asthma. Neither is as effective as the inhaled β2- agonists for preventing EIB,
but they can be used in conjunction for patients not responding completely to
inhaled β2-agonists.
• Most patients experience improvement in 1 to 2 weeks, but it may take longer
to achieve maximum benefit. Patients should initially receive cromolyn or
nedocromil four times daily; after stabilization of symptoms the frequency may
be reduced to two times daily for nedocromil and three times daily for
cromolyn.
3 September 2015 36
37. Leukotriene Modifiers
• Zafirlukast (Accolate) and montelukast (Singulair) are oral leukotriene
receptor antagonists that reduce the proinflammatory (increased
microvascular permeability and airway edema) and bronchoconstriction
effects of leukotriene D4.
• In adults and children with persistent asthma, they improve pulmonary
function tests, decrease nocturnal awakenings and β2-agonist use, and
improve asthma symptoms. However, they are less effective in asthma than
low-dose inhaled corticosteroids.
• They are not used to treat acute exacerbations and must be taken on a regular
basis, even during symptom-free periods. The adult dose of zafirlukast is 20
mg twice daily, taken at least 1 hour before or 2 hours after meals; the dose
for children aged 5 through 11 years is 10 mg twice daily.
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38. • For montelukast, the adult dose is 10 mg once daily, taken in the evening
without regard to food; the dose for children aged 6 to 14 years is one 5-mg
chewable tablet daily in the evening.
• Zileuton is an inhibitor of leukotriene synthesis. The dose of zileuton tablets
is 600 mg four times daily with meals and at bedtime. The recommended
dose of zileuton extended-release tablets is two 600-mg tablets twice daily,
within 1 hour after morning and evening meals (total daily dose 2,400 mg).
• Use of zileuton is limited due to the potential for elevated hepatic enzymes
(especially in the first 3 months of therapy), and inhibition of the
metabolism of some drugs metabolized by CYP3A4 (e.g., theophylline,
warfarin).
• Serum alanine aminotransferase should be monitored before treatment and
then periodically thereafter
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39. COMBINATION CONTROLLER THERAPY
• The addition of a second long-term control medication to inhaled
corticosteroid therapy is one recommended treatment option in moderate
to severe persistent asthma.
• Single-inhaler combination products containing fluticasone propionate
and salmeterol or budesonide and formoterol are currently available. The
inhalers contain varied doses of the inhaled corticosteroid with a fixed
dose of the long-acting β2-agonist.
• The addition of a long-acting β2-agonist allows a 50% reduction in inhaled
corticosteroid dosage in most patients with persistent asthma.
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40. • Combination therapy is more effective than higher-dose inhaled
corticosteroids alone in reducing asthma exacerbations in patients with
persistent asthma.
• Leukotriene receptor antagonists also are successful as additive therapy in
patients inadequately controlled on inhaled corticosteroids alone and as
corticosteroid-sparing therapy. However, the magnitude of these benefits
is less than that reported with the addition of long-acting β2-agonists.
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41. Omalizumab
• Omalizumab is an anti-IgE antibody approved for the treatment of
allergic asthma not well controlled by oral or inhaled corticosteroids.
• The dosage is determined by the patient’s baseline total serum IgE
(international units/mL) and body weight (kg). Doses range from 150 to
375 mg given subcutaneously at either 2- or 4-week intervals.
• Because of its high cost, it is only indicated as step 5 or 6 care for patients
who have allergies and severe persistent asthma that is inadequately
controlled with the combination of high-dose inhaled corticosteroids and
long-acting β2-agonists.
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42. • Because it is associated with a 0.1% incidence of anaphylaxis, patients
should remain in the physician’s office for a reasonable period after the
injection because 70% of reactions occur within 2 hours. Some reactions
have occurred up to 24 hours after injection.
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