therapy basics asthma
TRANSCRIPT
ESTIMATED MORBIDITY FOR NON COMMUNICABLE DISEASES IN INDIA
(Nongkynrih B et al, JAPI 2004 Feb; 52: 118-123)
WHO, 2002 data
0
10000000
20000000
30000000
40000000
50000000
60000000
70000000
Cancer IHD Stroke Diabetes Chronic respiratory
disease
0.6 million
25 million
1 million
28 million
65 million65 million
Asthma
COPD54 m
80-85% of chronic respiratory diseases in our country are due to
ASTHMA & COPD
Respiratory DiseasesRespiratory Diseases
Allergic RhinitisAllergic RhinitisAsthmaAsthma COPDCOPD
No. of patients with Asthma
• Estimated prevalence of Asthma is increasing 50% every 10 years
30 CRORES 1.5 – 2 CRORES
A S T H M A
Lets understand the respiratory system…….
Asthma is a long term disease that affects the airways.
Tubes that carry air in and out of your lungs.
Parts of the respiratory system
Parts of the respiratory system (Contd…)
AIRWAYS
Parts of the respiratory system (Contd…)
Cross Section of Airway Wall
Classification of the nervous system
Nervous system
Peripheral Central
Somatic Autonomic
Sympathetic Parasympathetic
ALLERGY
A reaction to a specific substance which is foreign to the body.
Allergen is the substance which induces an allergic response.
Normal individual
• Allergen stimulates production of IgE, in equal no. to allergen.
• Allergen destroyed
Allergic individual
• Allergen stimulates excess production of IgE.
• Some Allergens get destroyed.
• Rest cause allergic reaction.
Triggers
Dust mite
Triggers factors are things that when inhaled can start asthma.
They can vary from person to person.
Dust
SmokeCigarette smoke
Smoke from firecrackers
Pollen From plantsAnimal
dander
Exercise
Cold air
Strong smells
Recognition of asthma triggers and Recognition of asthma triggers and
avoiding them avoiding them
is the first step towards controlling asthma…is the first step towards controlling asthma…
On entry of these triggers
The airways get narrower
Less air flows through the lungs
AIRWAY OBSTRUCTION(Blockage in the airways)
This causes symptoms like...........
Asthma Symptoms
Breathlessness or dyspnoea (especially at night or after some exertion)
Wheezing (a whistling sound while breathing out)
Cough (especially at night or after some exertion)
Chest tightness (feeling of congestion)
Definition
Asthma is a
Chronic Inflammatory Disease characterized by
Airway Hyperresponsiveness to a variety of stimuli resulting in
Bronchospasm which reverses, spontaneously
or with treatment.
ABC of AsthmaA
Airway hyper-responsiveness (Airways over-react to triggers)
B Bronchospasm
(Sudden constriction in bronchial tubes)
C Chronic inflammation
(Long term swelling)
Exercise Induced Asthma (EIA)
Asthma attacks which occur after strenuous exercise. EIA symptoms occur after 3-8 min of exertion
Nocturnal Asthma
• Nighttime symptoms of wheezing, cough, breathlessness is known as nocturnal asthma.
• 70% of deaths due to asthma occur at night.
Causes of Nocturnal Asthma
- Exposure to dust mite, animal dander
- Gastro-oesophageal reflux
- Post nasal drip
- Increased parasympathetic activity
- Increased sensitivity to histamine
Diagnosing Asthma
1. History taking
2. Measurements of lung function
3. Bronchodilator reversibility test
1. History taking (Ask questions to Diagnose Asthma)
Does the patient have a troublesome cough, worse particularly at night, or on awakening?
Does the patient cough after physical activity (e.g.. Playing)?
Does the patient have breathing problems during a particular season (or change of season)?
Do the patient’s colds ‘go to the chest’ or take more than 10 days to resolve?
Does the patient use any medication (e.g. bronchodilator) when symptoms occur? Do you get relief?
If the patient answers “YES” to any of the above questions, suspect Asthma.
Also a doctor should ask about: Does anyone else in your family suffer
from Asthma, Allergies, Frequent Colds ?
2. Measurements of lung function
The Peak Flow Meter
The thermometer for Asthma
1. Measure peak flow reading
2. Give bronchodilator
4. Measure peak flow reading again
3. Wait for 10 to 15 minutes
5. If: 15 – 20 % increase in this reading from previous
6. Indication of a significant degree of reversible airflow
obstruction
ASTHMAASTHMA
3. Bronchodilator reversibility test
Peak Flow Master
• Diagnose asthma >15 % improvement in PEFR
( Reversibility )
• Monitoring > 20 % variability in AM-PM PEFR
indicates poor control
• To determine effectiveness of therapy
• Identify factors which worsen asthma
• Warn of an impending attack
• Incentive for the patients
Inflammatory Cells
Granulocytes Agranulocytes
RBCs WBCs Platelets
Eosinophils
Neutrophils
Basophils
Mast cells
Lymphocytes
(T cells & B cells)
Monocytes
Macrophages
INFLAMMATION
Treatment of Asthma
Routes of administration of anti-asthma drugs
Oral Inhaled Parenteral
Tablets
Syrup
Metered dose inhaler (MDI)
Dry powder inhaler (DPI)
Injections
Which is the best route for anti-asthmatic drugs???
Nebulizers
EyesEyes
SkinSkinNasal blockageNasal blockage
LungsLungs
Eye Drops Ear Drops
Lotions / ointments Nasal inhaler
INHALERS
NOT ORALS
EarsEars
ORAL OR INHALED
For Example…..
• Tab ASTHALIN 4mg = 4000 mcg
• 100mcg/Puff ASTHALIN x 2 puff = 200 mcg
20 times less drug is required for
desired effect from INHALATION route!
4000/200 = 20
ORAL OR INHALED
Oral
• Large dosage used
• Greater side effects
• Slow onset of action
• Not useful in acute symptoms
Inhaled
• Small amount of dosage used
• Lesser side effects
• Fast onset of action (e.g. bronchodilators)
• Useful in acute symptoms
ORAL OR INHALED
Advantages of inhalation therapy over oral route
Direct action in lungsSmall doses requiredQuick onset of ActionMinimum side effects
Asthma DiseaseBronchospasm & Inflammation (Swelling)
• Bronchospasm needs a Reliever Bronchodilator
• Inflammation (Swelling) needs a Controller
Anti-inflammatory
Drug treatment
Bronchodilators Anti-inflammatory
Relievers Controllers
Duration of action: shortshort Duration of action: longlong
Onset of action: faster Onset of action: slower
Quickly relieve symptoms Prevent asthma attacks
Rescue medicine Regular medicine
AVAILABLE DRUGS
RELIEVERSShort acting
bronchodilators
CONTROLLERSLong acting
bronchodilators Inhaled CorticosteroidsCombination Therapy Anti Leukotrienes
CiplaAVAILABLE RELIEVERS
Short acting bronchodilators
Salbutamol - ASTHALIN Levosalbutamol - LEVOLIN
To be taken as and when required
Cipla AVAILABLE CONTROLLERS
Inhaled corticosteroids
Beclomethasone BECLATE
Budesonide BUDECORT
Fluticasone FLOHALE
Ciclesonide CICLOHALE
Long acting bronchodilators
Salmeterol SEROBID
Formoterol FORATEC
Anti-leukotrienesMontelukast MONTAIR
To be taken regularly ,whether patient has symptoms or not
ICS + bronchodilators
SEROFLO – Salmeterol / Fluticasone FORACORT – Budesonide / FormoterolSIMPLYONE – Ciclesonide / Formoterol
FULLFORM – Beclomethasone / Formoterol BEKFORM - Beclomethasone / Formoterol AEROCORT - Beclomethasone / Salbutamol
To be taken regularly ,whether patient has symptoms or not
Cipla AVAILABLE CONTROLLERS (Contd…)
THE STORY OF ASTHMA TREATMENT
Traditional treatmentOccasional RelieversIdeal treatment
Regular ControllersSteroid
Mechanism of Action
Inhalation Therapy in Asthma
MOA of Bronchodilators
• Beta2-Agonists
• Short acting beta2-agonists
- Salbutamol
- Levosalbutamol
• Long acting beta2-agonists
- Salmeterol
-Formoterol
Mode of action of ß2 agonists
Smooth
muscle cell
Smooth musclecell relaxation
- agonist
Activates Proteinkinase
Decreasesintracellular Ca
2+
cAMP
ATP
2
2 -receptor
Mode of action of inhaled corticosteroids
Mode of action of inhaled corticosteroidsMode of action of inhaled corticosteroids
S Steroid
CELL
Steroidreceptor
NUCLEUSDNA
S
New Protein Synthesis
lipocortin
phospholipase A
(inhibits)
phospholipid arachidonic acid
leukotrienes prostaglandins
complexS
Classification of Severity-GINA
CLASSIFY SEVERITYClinical Features Before Treatment
SymptomsSymptoms NocturnalNocturnalSymptomsSymptoms FEVFEV1 1 or PEFor PEF
STEP 4STEP 4
Severe Severe PersistentPersistent
STEP 3STEP 3
Moderate Moderate PersistentPersistent
STEP 2STEP 2
Mild Mild PersistentPersistent
STEP 1STEP 1
IntermittentIntermittent
ContinuousContinuous
Limited physical Limited physical activityactivity
DailyDailyAttacks affect activityAttacks affect activity
> 1 time a week > 1 time a week but < 1 time a day but < 1 time a day
< 1 time a week< 1 time a week
Asymptomatic and Asymptomatic and normal PEF normal PEF between attacksbetween attacks
FrequentFrequent
> 1 time week> 1 time week
> 2 times a month> 2 times a month
2 times a month2 times a month2 times a month2 times a month
60% predicted60% predicted
Variability > 30%Variability > 30%
60 - 80% predicted 60 - 80% predicted
Variability > 30%Variability > 30%
80% predicted80% predicted
Variability 20 - 30%Variability 20 - 30%
80% predicted80% predicted
Variability < 20%Variability < 20%
The presence of one feature of severity is sufficient to place patient in that category.The presence of one feature of severity is sufficient to place patient in that category.
Stepwise Approach to Asthma Therapy - AdultsStepwise Approach to Asthma Therapy - Adults
Reliever: Rapid-acting inhaled β2-agonist prn
Controller: Daily inhaledcorticosteroid
Controller: Daily inhaled
corticosteroid Daily long-acting
inhaled β2-agonist
Controller: Daily inhaled
corticosteroid Daily long –acting
inhaled β2-agonist plus (if needed)
When asthma is controlled, reduce therapy
Monitor
STEP 1:STEP 1:IntermittentIntermittent
STEP 2:STEP 2:Mild PersistentMild Persistent
STEP 3:STEP 3: Moderate Moderate PersistentPersistent
STEP 3:STEP 3: Moderate Moderate PersistentPersistent
STEP 4:STEP 4:Severe Severe
PersistentPersistentSTEP DownSTEP DownSTEP DownSTEP Down
Outcome: Asthma Control Outcome: Best Possible Results
Controller:None
-Theophylline-SR -Anti-Leukotriene -Long-acting inhaled β2- agonist -Oral corticosteroid
New GINA guidelines:Focus on Asthma Control rather than severity
Global Initiative for Asthma (GINA) 2006
Characteristic Controlled(All of the following)
Partly Controlled(Any measure present in any
week)
Uncontrolled
Daytime symptoms None (twice or less/week)
More than twice/week
Three or more features of partly
controlled asthma present
in any week
Limitations of activities
None Any
Nocturnal symptoms/awakening
None Any
Need for reliever/rescue treatment
None (twice or less/week)
More than twice/week
Lung function (PEF or FEV1)
Normal < 80% predicted or personal best (if
known)
Exacerbations None One or more/year One in any week
MANAGEMENT APPROACH BASED ON CONTROL
Level of control Treatment Action
Reduce
Controlled Maintain and find lowest controlling step
Partly controlled Consider stepping up to gain control
Uncontrolled Increases Step up until controlled
Exacerbation Treat as exacerbation
Treatment Steps
The New Dimension
In
ASTHMA
CONTROLLERS
Combination TherapyCombination Therapy
THE CHANGE IN VIEW OVER YEARS
Time Period Goal of Management Preferred Medication
1960’s Relieve Bronchospasm
Epinephrine, Salbutamol, Levosalbutamol
1990’s Prevent and resolve inflammation
Inhaled glucucorticosteroids
Leukotriene modifiers
2000’s Resolve symptoms and disease process
Combination of ICS and LABAs
• It is now well accepted that asthma is an inflammatory diseases of the airways
• The bronchoconstriction that gives rise to dyspnoea is effect of the inflammatory process.
• It is no longer considered sufficient to treat the episodes of respiratory distress as and when they occur except in very mild cases.
• Shift in the focus of treatment
Bronchodilator Anti-inflammatory
Indian Pediatr 1998; 35: 871-881
Inhaled steroids and risk of death (NEJM, 2000)
Factor for Poor response to inhaled corticosteroids
• No immediate symptomatic relief• Resulting in low rates of compliance• No benefit in increasing the dose of ICS
beyond a particular dose
• Flat dose – response curve
• Local side effects (hoarseness, URTIs)
• Systemic side effects (cataracts / growth
retardation/ osteoporosis)
Favorable Benefiit-Risk Ratio
Wanted Effects
Dose
Unw
ante
d E
ffect
s
Flat Dose Response of ICS
1600mcgbudesonide
Response
Combination Therapy
Use of ICS and LABA is accepted as the most effective treatment regime to control moderate and severe asthma
Rationale for Combination Therapy
A fixed dose combination of a
long-acting beta2-agonist and
an inhaled corticosteroid
Complementary Action
• Corticosteroids and LABA act on two different
components of asthma.
• Inflammation can be taken care of by steroids
and
• Abnormalities in the bronchial smooth muscle
by LABA.
Synergistic Activity
• Beta2-agonists are potent activators of
the GC receptor.
• In addition, regular use of inhaled corticosteroids helps in increasing the activity of Beta 2-agonists
1) ICS enters the cell membrane, targets the intracellular inactive steroid receptor and binds to it
2) This leads to formation of an active receptor complex
…..which then binds to a target gene and the result is anti-inflammatory activity.
4) Synthesis of beta-2 receptor protein which is then inserted in the cell membrane.
5) LABA interacts with this membraneassociated beta-2 receptor
6) The subsequent beta-2 submit then interacts with the inactive corticosteroid receptor leading to a priming of
the receptor. This primed receptor is more susceptible to activation with steroids and importantly it requires less steroid then to convert the primed receptor to the active
receptor
Co deposition
Co-deposition of LABA and steroid
when administered in a single inhaler.
Flat Dose Response
• Inhaled steroids have a flat dose
response curve. Thus, addition of LABA
to a low dose of inhaled steroid is an
attractive therapeutic option to increasing
the dose of steroid.
Guidelines
• Prevents tolerance development
• Use of such a combination is in accordance with current guidelines for the management of asthma
Patient Compliance
• Simplifies therapy
• Improves compliance since only one inhaler is used
Reduced Cost
• Reduces cost of therapy due to better control of asthma and a better quality of life
Rationale of Combination Therapy-RECAP
• Complementary Action
• Synergistic Action
• Co- Deposition
• Taking care of Flat Dose Response
• Guidelines Recommendation
• Patient Compliance
• Reduced Cost
Combination therapy
• Formoterol ( fast relief and sustained relief )
+
• Budesonide ( twice or even once daily use )
Dose: 1- 4 inhalations ( OD/BD )
Combination therapy• salmeterol (sustained relief )
+
• fluticasone ( 3 times more potent than
budesonide )
Dose: 1- 2 inhalations (BD )
Combination therapy
• Formoterol ( fast relief and sustained relief )
+
• Ciclesonide ( the ideal ICS )
Dose: 1- 4 inhalations ( OD/BD )
Airway Remodeling
• Permanent structural changes in the airway wall which are irreversible.
• Increased mucus production• Fibrosis• Neovascularization
Goals of Asthma Therapy
• Minimal (ideally no) chronic symptoms
• Minimal (ideally no) need for “as needed” use of relievers
• No emergency visits
• (Near) normal PEF
• Minimal (infrequent) exacerbations
• PEF circadian variation of less than 20 percent
• No limitations on activities, including exercise
• Minimal (or no) adverse effects from medicine
MUST KNOW
• Routes of administration of anti-asthma drugs
• Advantages of inhalation therapy over oral route
• Drug therapy for asthma
• Differences between relievers and controllers
• Cipla’s available relievers & controllers