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Potenciais alvos de distúrbios patológicos do
aparelho respiratório
Doença Pulmonar
Obstrutiva: aumento na resistência ao fluxo aéreo.
1. Asma
2. Doença pulmonar obstrutiva crônica
a) Bronquite crônica
b) Enfisema pulmonar
Restritiva: redução da expansão do parênquima pulmonar
1. Síndrome do desconforto respiratório agudo (SDRA)
Asma
© Global Initiative for Asthma
Asthma is one of the most common chronic diseases worldwide
with an estimated 300 million affected individuals
Prevalence is increasing in many countries, especially in
children
Asthma is a major cause of school and work absence
Health care expenditure on asthma is very high
Burden of asthma
GINA 2014
© Global Initiative for Asthma
Asthma is a common and potentially serious chronic disease
that can be controlled but not cured
Asthma causes symptoms such as wheezing, shortness of
breath, chest tightness and cough that vary over time in their
occurrence, frequency and intensity
Symptoms are associated with variable expiratory airflow,
i.e. difficulty breathing air out of the lungs due to
Bronchoconstriction (airway narrowing)
Airway wall thickening
Increased mucus
Symptoms may be triggered or worsened by factors such as
viral infections, allergens, tobacco smoke, exercise and stress
What is known about asthma?
GINA 2014
© Global Initiative for Asthma
Asthma is a heterogeneous disease, usually characterized
by chronic airway inflammation.
It is defined by the history of respiratory symptoms such as
wheeze, shortness of breath, chest tightness and cough
that vary over time and in intensity, together with variable
expiratory airflow limitation.
Definition of asthma
NEW!
GINA 2014
© Global Initiative for Asthma
The diagnosis of asthma should be based on:
A history of characteristic symptom patterns
Evidence of variable airflow limitation, from bronchodilator
reversibility testing or other tests
Document evidence for the diagnosis in the patient’s notes,
preferably before starting controller treatment
It is often more difficult to confirm the diagnosis after treatment has
been started
Asthma is usually characterized by airway inflammation
and airway hyperresponsiveness, but these are not
necessary or sufficient to make the diagnosis of asthma.
Diagnosis of asthma
GINA 2014
© Global Initiative for Asthma
Note: Each FEV1 represents the highest of
three reproducible measurements
Typical spirometric tracings
Time (seconds)
Volume
FEV1
1 2 3 4 5
Normal
Asthma
(after BD)
Asthma
(before BD)
GINA 2014
© Global Initiative for Asthma
The long-term goals of asthma management are
1. Symptom control: to achieve good control of symptoms
and maintain normal activity levels
2. Risk reduction: to minimize future risk of exacerbations,
fixed airflow limitation and medication side-effects
Goals of asthma management
GINA 2014
Eosinófilos
Eosinófilos e asma
Asmatico Normal
Busse & Lemanske, N. Engl. J. Med, 2001,
Reação alérgica e asma
Dose-response curves to inhaled direct agonists (histamine or methacholine) in normal, mild,
or severe asthma.
Busse W W Chest 2010;138:4S-10S
Hiperreatividade brônquica – Asma
Mecanismos indutores de hiperreatividade
Receptores muscarínicos
e hiperreatividade
Doença Pulmonar
Obstrutiva: aumento na resistência ao fluxo aéreo. 1. Asma
2. Doença pulmonar obstrutiva crônica
a) Bronquite crônica
b) Enfisema pulmonar
Restritiva: redução da expansão do parênquima pulmonar
1. Síndrome do desconforto respiratório agudo (SDRA)
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition of COPD
COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.
.
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Mechanisms Underlying
Airflow Limitation in COPD
Small Airways Disease
• Airway inflammation • Airway fibrosis, luminal plugs • Increased airway resistance
Parenchymal Destruction
• Loss of alveolar attachments • Decrease of elastic recoil
AIRFLOW LIMITATION © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Burden of COPD
COPD is a leading cause of morbidity and mortality worldwide.
The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world’s population.
COPD is associated with significant economic burden.
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Risk Factors for COPD
Lung growth and development
Gender
Age
Respiratory infections
Socioeconomic status
Asthma/Bronchial hyperreactivity
Chronic Bronchitis
Genes
Exposure to particles
Tobacco smoke
Occupational dusts, organic and inorganic
Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings
Outdoor air pollution
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Spirometry: Normal Trace Showing FEV1 and FVC
1 2 3 4 5 6
1
2
3
4
Volu
me, lit
ers
Time, sec
FVC 5
1
FEV1 = 4L
FVC = 5L
FEV1/FVC = 0.8
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Volume expiratório forçado.
Capacidade vital forçada
The characteristic symptoms of COPD are chronic and progressive dyspnea,
cough, and sputum production that can be variable from day-to-day.
Dyspnea: Progressive, persistent and characteristically worse with exercise.
Chronic cough: May be intermittent and may be unproductive.
Chronic sputum production: COPD patients commonly cough up sputum.
Global Strategy for Diagnosis, Management and Prevention of COPD
Symptoms of COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: COPD Medications
Beta2-agonists
Short-acting beta2-agonists
Long-acting beta2-agonists
Anticholinergics
Short-acting anticholinergics
Long-acting anticholinergics
Combination short-acting beta2-agonists + anticholinergic in one inhaler
Combination long-acting beta2-agonists + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids
Phosphodiesterase-4 inhibitors
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Doença Pulmonar Obstrutiva Crônica Inflamação crônica e remodelamento das vias aéreas e
destruição do parênquima pulmonar.
Bronquite Crônica
Doença Pulmonar Obstrutiva Crônica Inflamação crônica e remodelamento das vias aéreas e
destruição do parênquima pulmonar.
Bronquite Crônica Spina. D, 2011
Doença Pulmonar Obstrutiva Crônica
Enfisema
Enfisema
Metaloproteinases: degradam componentes da matriz extracelular
Patologia da DPOC
Spina. D, 2011
Global Strategy for Diagnosis, Management and Prevention of COPD
Differential Diagnosis: COPD and Asthma
COPD
• Onset in mid-life
• Symptoms slowly progressive
• Long smoking history
ASTHMA
• Onset early in life (often childhood)
• Symptoms vary from day to day
• Symptoms worse at night/early morning
• Allergy, rhinitis, and/or eczema also present
• Family history of asthma
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
© Global Initiative for Asthma
Definitions
Asthma
Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation. It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation. [GINA 2014]
GINA 2014, Box 5-1
Asthma
Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation. It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation. [GINA 2014]
COPD
COPD is a common preventable and treatable disease, characterized by persistent
airflow limitation that is usually progressive and associated with enhanced chronic
inflammatory responses in the airways and the lungs to noxious particles or gases.
Exacerbations and comorbidities contribute to the overall severity in individual
patients. [GOLD 2014]
Asthma
Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation. It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation. [GINA 2014]
COPD
COPD is a common preventable and treatable disease, characterized by persistent
airflow limitation that is usually progressive and associated with enhanced chronic
inflammatory responses in the airways and the lungs to noxious particles or gases.
Exacerbations and comorbidities contribute to the overall severity in individual
patients. [GOLD 2014]
Asthma-COPD overlap syndrome (ACOS) [a description]
Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow
limitation with several features usually associated with asthma and several features
usually associated with COPD. ACOS is therefore identified by the features that it
shares with both asthma and COPD.
Síndrome do Desconforto Respiratório Agudo
(SDRA)
Lesão capilar alveolar difusa
Insuficiência respiratória grave
Hipoxemia arterial grave (refrataria a oxigenoterapia)
Cianose
Falência múltipla dos órgãos
Andrew, et al. Am J Physiol Lung Cell Mol Physiol 306: L217–L230, 2014
Modulação farmacológica (Distúrbios patológicos - aparelho respiratório)
Pharmacological therapies for acute respiratory
distress syndrome
(SDRA)
Peter Markus Spietha and Haibo Zhang
Antagonistas de leucotrienos peptidicos (LTD4)
UTILIZADOS
PRINCIPALMENTE EM
SITUAÇÕES
EMERGENCIAIS
MUITO IMPORTANTES NA
FASE INICIAL NO
PROCESSO ASMÁTICO
METILXANTINAS
PROVAVELMENTE
ELEVANDO OS NÍVEIS
DE AMP CÍCLICO E/OU
BLOQUEANDO OS
RECEPTORES DA
ADENOSINA
ANTAGONISTAS
COLINÉRGICOS
(ANTICOLINÉRGICOS)
BLOQUEANDO RECEPTOR
COLINÉRGICO
MUSCARÍNICO
AGONISTAS
ADRENÉRGICOS
BRONCODILATAÇÃO POR
ESTÍMULO DE
RECEPTORES BETA 2
Agonistas de Receptores adrenérgicos
Metil xantinas
(Teofilina e Aminofilina)
Mecanismo de ação:
Inibição da fosfodiesterase (cAMP)
Altera concentração Ca++
Efeitos adversos
Estimulação do coração
Estimulante SNC
Náusea, vômitos, tremores
ATP cAMP 5’-AMP
Adenylyl Cyclase Phosphodiesterase
agonists
stimulate Teophylline
inhibits
inhibition of mediator release
bronchodilation
Antagonistas de Receptores de LT peptídicos
Glicocorticóides
Modulação farmacológica (Distúrbios patológicos - aparelho respiratório)
Antagonistas - receptores muscarinicos
Controle neural das vias aéreas
Colinérgico
Atropina
Brometo de ipatropio
Tiotropium
Receptores
Fármacos Anticolinérgicos
Fármacos Mucoativos
Fármacos que facilitam a eliminação do
muco das vias aéreas superiores.
Muco é um polímero de mucina altamente
oligomerizado composto de água e varias
glicoprotenas macromoleculares.
Fármacos Mucoativos
Fármacos Mucoativos
Expectorantes: Estimulam o fluxo da secreção e diminuiem a viscosidade do muco : GUAIFENESINA (Xarope Vick) Mucoreguladores: Diminuem o volume de secreção: AGENTES ANTICOLIÉERGICOS (Brometo de ipatropio) Mucolíticos: Quebram as pontes dissulfeto que ligam os polímeros de mucina: N-ACETIL CISTEINA (Fluimucil) Mucocinéticos: Estimulam a produção de surfactante e inibem os canais de sódio neuronal : AMBROXOL (Mucosolvan)