This document provides an overview of asthma, including its causes, pathophysiology, diagnosis, classification, management, and new drug developments. Key points include: Asthma is a chronic inflammatory disease characterized by variable airflow obstruction; it is caused by genetic and environmental factors. Management involves identifying triggers, medications like corticosteroids and beta-agonists, and new targeted therapies like monoclonal antibodies are being developed.
Reference:
K. D. Tripathi. Essentials of Medical Pharmacology, 6th edition. Jaypee Publication Pg. No. 213-230.
This slide deck give detail presentation on causes, pathophysiology and pharmacotherapy of bronchial asthma.
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Educational and therapeutic topic on asthma for MBBS and MD pharmacology students. other students like BDS , BHMS, BAMS etc can use for knowledge. and academic purpose.
Reference:
K. D. Tripathi. Essentials of Medical Pharmacology, 6th edition. Jaypee Publication Pg. No. 213-230.
This slide deck give detail presentation on causes, pathophysiology and pharmacotherapy of bronchial asthma.
For all IV video lecture series of this topic click:
https://youtube.com/playlist?list=PLBVbJ9HCa1BYdASIBMWSjjSL7zVHHVW1l
- For More Such Learning You Can Subscribe to My YouTube Channel.
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Facebook Page: https://www.facebook.com/asacademylearningforever
Website Blog: https://itasacademy.blogspot.com/
Educational and therapeutic topic on asthma for MBBS and MD pharmacology students. other students like BDS , BHMS, BAMS etc can use for knowledge. and academic purpose.
#Bronchial asthma
#Drugs for bronchial asthma
#Mechanism of action of β2 receptor agonists in Bronchial Asthma
#Mechanism of action of Methylxanthines in Bronchial Asthma
#Mechanism of action of Anticholinergics in Bronchial Asthma
#Mechanism of action of Leukotriene antagonists in Bronchial Asthma
#Mechanism of action of Mast cell stabilizers in Bronchial Asthma
#Mechanism of action of Corticosteroides in Bronchial Asthma
#Bronchial asthma
#Drugs for bronchial asthma
#Mechanism of action of β2 receptor agonists in Bronchial Asthma
#Mechanism of action of Methylxanthines in Bronchial Asthma
#Mechanism of action of Anticholinergics in Bronchial Asthma
#Mechanism of action of Leukotriene antagonists in Bronchial Asthma
#Mechanism of action of Mast cell stabilizers in Bronchial Asthma
#Mechanism of action of Corticosteroides in Bronchial Asthma
Asthma is a condition in which your airways narrow and swell and may produce extra mucus.
This can make breathing difficult and trigger coughing, a whistling sound (wheezing)
when you breathe out and shortness of breath
Asthma is a major noncommunicable disease (NCD), affecting both children and adults, and is the most common chronic disease among children.
Inflammation and narrowing of the small airways in the lungs cause asthma symptoms, which can be any combination of cough, wheeze, shortness of breath and chest tightness.
Asthma affected an estimated 262 million people in 2019 (1) and caused 455000 deaths.
Definition and introduction to bronchial asthma - classification of bronchial asthma - pathophysiology and risk factors for bronchial asthma - diagnosis of bronchial asthma - clinical manifestations - investigations - management of bronchial asthma
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
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
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
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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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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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
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Asthma presentation and management
1. PHARMACOLOGY OF ASTHMA AND ADVANCES IN ITS
MANAGEMENT
A SEMINAR PRESENTED
BY
JOSEPH, OYEPATA SIMEON (Ph.D)
2. INTRODUCTION
Asthma is a common chronic inflammatory disease of the
airways characterized by variable and recurring symptoms,
reversible airflow obstruction and bronchospasm.
Asthma is thought to be caused by a combination of genetic
and environmental factors. Its diagnosis is usually based on
the pattern of symptoms, response to therapy over time
and spirometry.
3. Figure 1: shows the location of the lungs and airways in the body
4. Asthma is one of the major noncommunicable
diseases. WHO 235–300 million people globally are
diagnose with asthma, and it caused 250,000 deaths
(WHO, 2013).
5. Causes of asthma
Asthma is caused by a combination of complex and incompletely understood environmental and
genetic interactions.
Causes include
Environmental
Genetic
Drug use
Hygiene hypothesis
Medical conditions
Exercise-induced
Occupational
6. Asthma Pathophysiology
Most patients do experience 2 clear phases of the asthmatic response when
exposed to a particular trigger, the “early” phase and the “late” phase.
The “early” phase of the asthma response usually occurs 10-30 minutes
following exposure to an asthma trigger and involves the release of
inflammatory mediators from IgE-coated mast cells throughout the respiratory
passages
These mediators induce bronchospasm and increase permeability of the
airways to antigen
Abnormal activation of the parasympathetic nervous system also seems to
occur during the early phase of the asthmatic response. Activation of
vagal nerves in the airway constricts bronchial smooth muscle and
increases secretions from mucous-producing cells
7. Neutrophils, attracted by chemotaxis to the area of inflamed airway, leave
the more permeable blood vessel and enter the respiratory tissues
Neurophils are joined by other inflammatory immune cells such as
basophils, and eosinophils that escalate the inflammatory response by
releasing their own inflammatory mediators
T-lymphocytes may also play an important role in the asthmatic response
since a particular subset of T-lymphocytes (TH2) responds to
environmental allergens by releasing cytokines that are involved in the
formation of IgE-producing plasma cells. This heightened period of
inflammation constitutes the “late” phase of asthma response and can last
for hours to days
8. The heightened airway inflammation that occurs during
the late phase of asthma leads to marked airway
edema, impaired mucociliary function, and further
impaired movement of airflow. If severe or prolonged,
the inflammation associated with asthma can damage
respiratory epithelium and lead to a pathologic
remodeling of the airways.
9. Figure 2: Components of the early phase of asthma.
10. Figure 3: Components of the late phase of asthma.
11. Diagnosis
A diagnosis of asthma should be suspected if
there is a history of recurrent wheezing,
coughing or difficulty breathing and these
symptoms occur or worsen due to exercise, viral
infections, allergens or air pollution.
Spirometry is then used to confirm the diagnosis.
In children under the age of six the diagnosis is
more difficult as they are too young for
spirometry
12. Classification
Clinical classification (≥ 12 years old)
Severity Symptom
frequency
Night time
symptoms
%FEV1 of
predicted
FEV1
Variability
SABA use
Intermittent ≤2/week ≤2/month ≥80% <20% ≤2 days/week
Mild persistent >2/week 3–4/month ≥80% 20–30% >2 days/week
Moderate Daily >1/week 60–80% >30% daily
Severe persistent Continuously Frequent
(7×/week)
<60% >30% ≥twice/day
13. Severity of an acute exacerbation
Near-fatal High PaCO2 and/or requiring mechanical
ventilation
Life-threatening
(any one of)
Clinical signs
Measure
ments
Altered level of consciousness
Peak flow
< 33%
Exhaustion
Oxygen
saturation
< 92%
Arrhythmia
PaO2 < 8
kPa
Low blood pressure
"Normal"
PaCO2
Cyanosis
Silent chest
Poor respiratory effort
Acute severe
(any one of)
Peak flow 33–50%
Respiratory rate ≥ 25 breaths per minute
Heart rate ≥ 110 beats per minute
Unable to complete sentences in one breath
Moderate Worsening symptoms
Peak flow 50–80% best or predicted
No features of acute severe asthma
14. Differential diagnosis
Chronic obstructive pulmonary disease can
coexist with asthma and can occur as a
complication of chronic asthma
COPD can be differentiated by increased airway
neutrophils, abnormally increased wall thickness,
and increased smooth muscle in the bronchi.
15. Prevention
limiting smoke exposure both in utero and after delivery, breastfeeding, and increased
exposure to day care or large families but none are well supported enough to be
recommended.
Early pet exposure may be useful
Reducing or eliminating compounds known to sensitive people from the work place may
be effective.
It is not clear if annual influenza vaccinations effects the risk of exacerbations.
Immunization; however, is recommended by the World Health Organization.
Smoking bans are effective in decreasing exacerbations of asthma
16. Management
While there is no cure for asthma, symptoms can typically
be improved
The most effective treatment for asthma is identifying
triggers, such as cigarette smoke, pets, or aspirin, and
eliminating exposure to them. If trigger avoidance is
insufficient, the use of medication is recommended
Specific medications for asthma are broadly classified
into fast-acting and long-acting categories.
19. Specific β2 agonists
Specific β2 agonists exert their beneficial effects
through relaxation of bronchial smooth muscle. These
agents bind to G-protein-linked cell surface receptors
in the airways.
Activation of β2 receptors leads to the activation of
adenylate cyclase and subsequent generation of cyclic
AMP (cAMP). Increased levels of cAMP in turn activate
protein kinase A which induces calcium extrusion and
sequestration and thus smooth muscle relaxation.
20. Adverse effects of short term use of specific β2 agonists
are relatively minor and infrequent due to their high
specificity and topical delivery.
Beta-2 adrenergic receptors in bronchial smooth
muscle seem to be somewhat resistant to
desensitization, while those on mast cells and
lymphocytes appear more susceptible to this
phenomenon.
The potential for adverse effects is greater when these
agents are used orally and may include muscle tremors
and cramps, cardiac effects and metabolic changes.
21. Corticosteroids
Corticosteroids exert multiple antiinflammatory
actions including inhibition of inflammatory cytokine
release and reduced activity of inflammatory immune
cells. E.g. of corticosteroid are Fluticasone propionate
and beclomethasone.
Several inhibitor proteins such as annexins and
lipocortins are generated in response to
corticosteroid receptor binding, which appear to
inhibit the release of the arachidonic acid substrate
from membrane lipids.
22. Corticosteroids also interact with specific
receptors in tissues to regulate expression of
corticosteroid-responsive genes.
Side effects of oral corticosteroid uses may
include endocrine suppression, increased risk of
infections, osteoporosis, osteonecrosis, cataract
formation, fluid and electrolyte imbalances and
impaired growth and development in children
23. Steroid resistance
5-10% of patients with severe asthma respond
poorly to a maximal dose of steroids.
A type of lymphocytes called natural helper (NH)
cells has been identified to plays a critical role in
corticosteroid resistance T lymphocytes and NH
cells in the asthmatic lung produce proteins
named interleukin (IL)-5 and IL-13 that are
responsible for severe airway inflammation.
24. However, in severe asthma patients, another protein called
interleukin-33 (IL-33) produced in the airways strongly
activates NH cells to produce IL-5 and IL-13, leading to
severe airway inflammation.
Research shows that NH resistance to steroids is induced by
the protein thymic stromal lymphopoietin (TSLP), present in
the airways of severe asthma patients
The drug, Pimozide, an approved anti-psychotic drug, was
found to restore the effects of steroids on NH cells.
25. Theophylline
There are several proposed mechanisms for the beneficial effect of theophylline in
asthma.
The first involves its ability to inhibit cyclic nucleotide phosphodiesterases which in turn
inhibits the degradation of cyclic AMP and cyclic GMP (Figure4). Increased levels of these
second messengers in turn lead to bronchodilation (similar to β2 agonists) as well as
decreased release of inflammatory mediators from mast cells.
A second proposed mechanism action of theophylline in asthma centers on its ability to
antagonize adenosine receptors in the airways.
26. At high doses they can cause marked CNS
stimulation, tremors, and even convulsions.
The cardiovascular effects of methylxanthines
are also significant and may include tachycardia,
increased cardiac output and, of greatest
concern with high blood levels, cardiac
arrhythmia and sudden death
27. Anticholinergic
Anticholinergic agents exert a bronchodilator effect
through blockade of muscarinic receptors in the airways.
Blocking cholinergic activity likewise blocks the increase in
mucous secretion that occurs in response to vagal
activation.
Anticholinergic bronchodilators can also be used if a
person cannot tolerate a SABA.
The major limiting factor to the use of atropine was its
potential for CNS penetration and cardiac effects
E.g. ipratropium bromide
28. Cromolyn sodium and derivative
Cromolyn sodium is a mast cell stabilizer.
The mechanism of action for these agents remains incompletely
understood. It is likely they exert multiple effects including inhibition of
mast cell release, altered parasympathetic response, altered leukocyte
function, and suppression of leukocyte chemotaxis.
The major use of these agents is to prevent asthma attacks in patients
with mild to moderate asthma.
Nedocromil is generally more effective at relieving asthma symptoms
than cromolyn and may reduce the amount of inhaled steroids used in
certain asthmatic patients.
30. Leukotriene antagonist
The first class of asthma drugs to be targeted to a specific component of the asthmatic
response were the leukotriene pathway inhibitors
leukotriene was found to play a key role in a number of inflammatory processes
including those associated with the asthmatic response
Studies have shown LTD4 to be nearly 100 times more potent than histamine in causing
bronchoconstriction.
Two strategies have been employed to block the actions of the leukotrienes in the
airways. The first involves direct inhibition of the enzyme 5-lipoxygenase, which is
responsible for the synthesis of leukotrienes e.g Zeleuton.
The second involves direct blockade of leukotriene receptors in the airways (E.g.
zafirlukast and montelukast).
31. Adverse effects for the leukotriene receptor
antagonists are low. A small percentage of
patients taking these agents have developed a
systemic vasculitis that is similar to Chrug-Strauss
syndrome.
Leukotriene receptor antagonists may be used in
addition to inhaled corticosteroids, typically also
in conjunction with a LABA
33. Another approach to the treatment of asthma involves the targeting of IgE, the main
immunoglobulin involved in the binding and degranulation of mast cells.
Omalizumab is designed to bind the Fc receptor on IgE, the same receptor that IgE uses
to bind to mast cell FC epsilon receptor I (FCεRI) (Figure (Figure6).6). Thus omalizumab is
essentially an antibody against an antibody.
Omalizumab binds free IgE with high affinity but does not interact with any IgE that is
already bound to mast cells and thus will not induce mast cell degranulation even if IgE
is already present on mast cells.
The adverse effects of omalizumab reported in controlled trials up to this point have
been relatively minor and include mainly injection site reactions. Less than 1% of patients
receiving omalizumab developed antibodies against the drug
34. others
Oxygen to alleviate hypoxia if saturations fall below
92%.
Magnesium sulfate intravenous treatment increases
bronchodilation when used in addition to other
treatment in severe acute asthma attacks.
Heliox, a mixture of helium and oxygen, may also be
considered in severe unresponsive cases.
35. Alternative medicine
Evidence is insufficient to support the usage of Vitamin C. There
is tentative support for its use in exercise induced
brochospasm.
Acupuncture is not recommended for the treatment as there is
insufficient evidence to support its use.
Manual therapies, including osteopathic, chiropractic,
physiotherapeutic and respiratory therapeutic maneuvers, have
insufficient evidence to support their use in treating asthma.
Air ionisers show no evidence that they improve asthma
symptoms or benefit lung function; this applied equally to
positive and negative ion generators.
36. For those with severe persistent asthma not controlled by
inhaled corticosteroids and LABAs, bronchial thermoplasty
may be an option
It involves the delivery of controlled thermal energy to the
airway wall during a series of bronchoscopies.
While it may increase exacerbation frequency in the first
few months it appears to decrease the subsequent rate
Effects beyond one year are unknown. Evidence suggests
that sublingual immunotherapy in those with both allergic
rhinitis and asthma improve outcomes.
37. New drug development for Asthma Pharmacotherapy.
One key component of chronic asthma that needs to be addressed
with new therapies is the prevention or reversal of airway remodeling.
The development of so called synthetic “soft” steroids has been an
active area of research (Belvisi and Hele 2003). These synthetic steroids
may take the form of inactive ester prodrugs that are converted to their
active form in the airways. One such agent, ciclesonide (Alvesco)
received preliminary FDA approval in 2003 and is still undergoing
extensive clinical testing. Early results indicate that systemic
bioavailability of this agent was negligible and that it did not suppress
cortisol secretion
38. Novel bronchodilator compounds such as vasoactive intestinal peptide
(VIP), atrial natriuretic peptide (ANP), and prostaglandin E analogs are
undergoing investigation. Despites some promising success, the main
draw of using peptides as therapeutic agents, their instability, still needs
to be overcome.
activation of adenosine receptor subtype A2A has inhibitory effects on
leukocyte activity and agonists of this specific receptor are under
investigation as well.
Cytokines such as interleukins (IL) and tumor necrosis factor alpha (TNF-
α) have been the subject of intensive recent investigation in a number of
inflammatory human conditions such as inflammatory bowel disease
and rheumatoid arthritis
39. Antagonism of 2 related cytokines, IL-4 and IL-13, have shown
more promising effects on asthma in early trials
Chemotactic cytokine called “chemokines” are also substances
of interest in asthma. Through interaction with cell surface
chemokine receptors (CCR), these substances (eg, eotaxin)
mobilize a number of immune cells such as eosinophils and
lymphocytes that are involved in the allergic asthmatic
response.
A number of potent and highly specific small molecule CCR
antagonists are under development (eg, SB-328437 from
Glaxo-SmithKline and RO116-9132/238 from Roche). Several of
these (eg, GSK 766994) have entered early clinical trials.
40. CONCLUSION
Given the wealth of new therapeutic targets
currently under investigation, the next
decade holds great promise (s) for the
development of new and effective asthma
drugs, particularly in the area of preventing
the detrimental long-term effects of airway
remodeling.