2. Contents-
Asthma- definition, Pathophysiology, Types
Principle of therapy
Aim of therapy
Classification of Antiasthmatics
Drug therapy during acute attack
Treatment of chronic persistent asthma
Severe acute asthma (Status asthmaticus )-treatment &
management
COPD
Difference between asthma and COPD
Bronchodilator regimens in COPD
3. Definition :
Bronchial asthma is a clinical syndrome characterised by :
- cough / paroxysmal dyspnea
- wheeze due to increased resistance to air flow through the narrowed
bronchi.
The narrowing of bronchi is due to :
- Bronchial hyper-reactivity and bronchospasm
- Cellular infiltration and edema of the bronchial mucosa
- Blockage of the bronchial lumen by inspissated mucus
4. Pathophysiology of asthma-
The etiology of asthma is multifactorial:
Genetic, developmental, environmental, inflammation and immunological.
Its pathogenesis is complex and involve – inflammation and re-modelling of the
airways.
5. Many patients have had well defined allergen exposures
which are partly or substantially responsible for the asthmatic
inflammation. These patient have inflamed airways and
infiltration with mast cells, eosinophilis, basophiles macrophages
and activated helper T lymphocyte.
Lymphocytes-directed eosinophilic bronchitis is the hallmark of
asthma.
Mediators released from the cells, damage the bronchial
epithelium.
6. Some important mediators released by mast cells and
leucocytes-
From granules
Histamine, Heparin
Trypsase, Chymotrypsin, Proteases
From membrane lipids
Sulfidopeptide leukotrienes
Prostaglandins, PAF
Proinflammatory cytokines
TNF α and interleukins 3,4,5 and 13
8. Extrinsic Intrinsic
1. It start in childhood or at early age. 1.it occur in middle aged subjects.
3. Associated with history of atopy
in patient’s childhood, a family history of
allergic, illness like hay fever, positive
skin tests.
2. no family history of allergies.
3. Usually manifests clinically in ‘episodic
form’.
3. clinically assumes a ‘chronic form’.
4.raised serum IgE level. 4. plasma IgE is not raised.
Asthma is considered as –
9.
10.
11. Principle of therapy:
Treatment is directed toward :
- relieving bronchospasm
- reducing the bronchial inflammation
Aim of therapy:
Prevention of repeated attacks and enabling the
subject to live as normal a life as possible, including
normal exercise tolerance without causing adverse
reaction.
12. The available therapeutic measure are:
- Elimination of the trigger factor
- Avoiding respiration irritant
- Drug therapy
- Correction of dehydration and acidosis in severe acute attack
- Controlled administration of oxygen, when needed
- Physical exercise
- Psychological treatment
Drug therapy should be given by Inhalation.
It is carried out by using :
- Pressurised, metered dose (aerosol) inhaler (MDI)
- Nebuliser
- Dry powder inhalers (DPI)
15. Drug therapy during an acute attack
Drugs used to produce quick relief from acute attack are called rescue
drugs – beta2 adrenergic receptor agonist.
These drugs :
- Relax the smooth muscles of all airways
- Enhance mucociliary clearance from the respiratory tract
- Supress the microvascular leakage in the airways
- Inhibit mediator release from the mast cells and the basophils
and cytokine release from the inflammatory cells in the airways
- Inhibit release of acetylcholine
16. Salbutamol
MOA - Selective beta-2 adrenergic agonist.
It has a prominent bronchodilator action of rapid onset.
It has poor cardiac (beta-1 receptor ) action.
It has resistance to inactivation by COMT and therefore has a longer duration
of action.
Methods of administration –
by pressurised metered dose inhalation (MDI) (dose 100 microgram / puffs)
Each inhalation improve the effectiveness of subsequent inhalations.
The dose must be prescribed clearly as “ so many puffs at a time and the maximum
number of puffs per day.”
Also given SC or IM in the dose of 0.5 mg every 4 hrs and IV slowly in the dose of
0.25 mg at the rate of 5-10 mcg /min.
Also administered by a nebuliser and a dry powder inhaler
17. ADR – tremor, anxiety, tachycardia
Levosalbutamol – Salbutamol is a recemate. The active
compound levosalbutamol is available in 50 mcg/puff MDI. It is
not clinically to salbutamol either in efficacy or ADR.
Isoetharine , terbutaline , fenoterol, bitolterol and rimiterol are
other selective short acting beta-2 agonists with similar
properties as salbutamol.
18. Aminophylline = Theophylline + ethylene diamine
MOA-
Cause bronchodilatation by its weak and non- selective inhibition of
pulmonary enzyme PDE-4.
Inhibits adenosine receptor in the airways.
Inhibits the late response to allergens.
Acts synergistically with beta adrenergic agonists.
Route-
Less effective orally becaue of it is absorbed , it undergoes first pass
metabolism.
Given rapidly IV, it may cause nausea, vomiting , cardiac arrhythmia
and collapse.
19. Drug interaction-
Ciprofloxacin, erythromycin increase the plasma
concentration of theophylline
Therapeutic uses -
1. Acute attack of asthma- dose – 5mg/kg over 15-30 min ; IV
2. Chronic persistent asthma- slow release oral preparation
useful in patient with persistent bronchospasm between acute
attacks and in preventing nocturnal attack.
20. Prevention of Acute attacks
The drugs used in the prevention of acute attack (maintenance therapy) are:
1. Inhaled long acting beta-agonist eg. Salmeterol, formoterol
2. Inhaled glucocorticoids
3. Oral theophylline
4. Oral leukotriene modifiers
Salmeterol
Long acting beta-2 partial adrenergic agonist weaker than salbutamol.
Drug of choice in the prevention of nocturnal asthmatic attacks and those induced by
exercise.
Not useful in relieving acute attack.
Dose – 1-2 puffs every 12 hrs
should not used more than twice a day.
21. Leukotriene modifiers
LT increase bronchial mucus secretion , decrease mucociliary
clearance and increase vascular permeability.
Drugs modify the LT system by-
1. Acting as competitive antagonist on type 1 cysteinyl LT
receptor eg. Montelukast
2. Blocking the LT synthesis eg. Zileuton
Leukotriene modifiers have no bronchodilator action and can not
be used as rescue drugs.
23. Treatment of chronic persistent asthma
Inhaled beta - agonist : Salmeterol and formoterol used.
Glucocorticoids
“First line therapy”
MOA -
Inhibit phospholipase A2
Stabilise the cellular lysosomal membrane
Inhibit the influx of inflammatory cells
Prevent and reserve the downregulation of the beta adrenergic
receptor
Inhibit the release of mediators from the macrophages
Long term administation also reduces the immediate response to
allergens and prevent exercise induced asthma
24. Important limitations of inhaled glucocorticoids are –
Small doses are highly effective , higher doses produce
limited additional benefits.
Long term use of high doses may cause systemic
adverse event such as osteoporosis, cataract, glaucoma and
growth retardation in children.
Locally they are cause sore throat, coughing,
hoarseness and rarely candidiasis.
25. Severe acute asthma (status asthmaticus) – treatment
Definition-
Status asthmaticus is a medical emergency , requiring urgent
hospitalization and vigorous therapy.
It is precipitated by –
An acute respiratory infection
Abrupt cessation of glucocorticoid therapy
Drugs (aspirin or NSAID) or inhaled allergens
Acute emotional stress
Life threatening features in status asthmaticus-
Silent chest , feeble respiratory efforts , cyanosis, bradycardia,
hypotention, exhaustion , confusion and coma
26. Management of severe acute asthma
Initial treatment
Correct dehydration
Humidified oxygen (50-60%) by mask
Nebulized salbutamol and ipratropium
Oral prednisolone or IV hydrocortisone
If poor response to above in 1 hr
Hospitalize
Correct dehydration and acidosis
Repeat nebulised salbutamol every 30 min
Repeat nebulised ipratropium
IV hydrocortisone
IV infusion of aminophylline or salbutamol
Monitor serum K+ , arterial oxygen saturation
Antibiotics for chest infection
Exclude pneumothorax(X- ray chest)
If still poor response after 1 hr
Shift to intensive care unit
27. COPD – Chronic Obstructive Pulmonary Disorder
Definition-
COPD is characterised by “air flow resistance that is not reversible”.
It include the following-
Emphysema, an anatomically defined entity associated with enlarged
and distorted lung alveoli.
Chronic bronchitis, a clinical entity associated with disease of small
bronchioles with a chronic air flow obstruction, chronic cough and marked
expectoration.
Chronic bronchitis without airflow obstruction is not COPD.
COPD is a complex syndrome which result in a slow , albeit
progressive loss of lung function due to chronic inflammation of the small
airways and lung parenchymatous tissue.
28. Difference between asthma and COPD
Asthma COPD
Airflow limitation Reversible unless
remodelling present
Mainly reversible
Age at onset Usually < 40 yrs Usually > 40 yrs
Site of disease Proximal airways Peripheral airways
Lung parenchyma
Bronchial hyper-
responsiveness
Increased Variable
Patient characteristics May or may not have
smoking history
Most have smoking history
Mast cell and eosinophils Increased Normal
Breathlessness Variable Persistent and progressive
29. The current therapy of COPD include the following -
1. Inhaled bronchodilator (beta-2 agonist, anticholinergic)
2. Inhaled glucocorticoids
3. Oxygen inhalation
4. Prophylactic antibiotics
5. Prevention of dehydration
6. Physiotherapy, pulmonary rehabilitation and education
Risk factor -
Smoking, indoor air pollution, biomass fuel
30. Bronchodilator regimens in COPD
Drug Duration of action Dose
Short acting
Salbutamol sulphate 4-6 2 puff every 4 h (MDI 100 mcg/puff)
Ipratropium bromide 4-6 2 puff every 4 h (MDI 20 mcg/puff)
Long acting
Formoterol 8-12 One inhalation twice a day (DPI 12
mcg/inhalation)
Salmeterol 8-12 One inhalation twice a day (DPI 50
mcg/inhalation)
Long- acting combination :
Steroids + beta-2- agonist
Fluticasone + Salmeterol 12 Two inhalations twice a day (MDI 45,
115,230 mcg fluticasone + 21 mcg
