2. Asthama
• Asthma is a long-term inflammatory disease of the
airways of the lungs.
• It is characterised by hyperresponsiveness of
tracheobronchial smooth muscle to a variety of
stimuli, resulting in narrowing of air tubes, often
accompanied by increased secretion, mucosal
edema and mucus plugging.
• Symptoms include episodes of wheezing, coughing,
chest tightness, and shortness of breath.
• Asthma is caused by a combination of complex and
incompletely understood environmental and
genetic interactions.
3. Causes
The causes may include
• Environmental
• Exacerbation
• Genetic
• Medical
• Asthma is the result of chronic inflammation of the
conducting zone of the airways , which subsequently results
in increased contractability of the surrounding smooth
muscles.
• Other cell types involved include T lymphocytes,
macrophages, and neutrophils. There may also be
involvement of other components of the immune system,
including cytokines, chemokines, histamine, and
leukotrienes among others.
4. Types
Atopic (childhood onset, extrinsic) asthma
• This occurs in children and young adults who have atopic
(type I) hypersensativity to foreign protein, e.g. pollen,
dust containing mites from carpets, feather pillows,
animal dander, fungi.
• It tends to be perennial, status asthmaticus is more
common.
• Non-atopic (adult onset, intrinsic) asthma
• This type occurs later in adult life and there is no history
of childhood allergic reactions. It is often associated with
chronic inflammation of the upper respiratory tract, e.g.
chronic bronchitis, nasal polyps
• It is mostly episodic, less prone to status asthmaticus.
5. Prevention
• APPROACHES TO TREATMENT
• 1. Prevention of AG:AB reaction—avoidance
• of antigen, hyposensitization—possible in extrinsic asthma and if antigen can be
identified.
• 2. Neutralization of IgE (reaginic antibody)—
• Omalizumab.
• 3. Suppression of inflammation and bronchial
• hyperreactivity—corticosteroids.
• 4. Prevention of release of mediators—mast
• cell stabilizers.
• 5. Antagonism of released mediators—leukotriene antagonists, antihistamines, PAF
• antagonists.
• 6. Blockade of constrictor neurotransmitter—
• anticholinergics.
• 7. Mimicking dilator neurotransmitter—sympathomimetics.
• 8. Directly acting bronchodilators—methylxanthines
7. Sympathomimetic drugs
These are selective beta2 agonist.
MOA- stimulation of beta 2 receptor
Increased cAMP formation in bronchial muscles
Less phosphorylation of myosin chain decreace the activity
of smooth muscle and cause bronchodilation
Eg. - salbutamol
Terbutaline
Salmeterol, etc.
8. Methyl Xanthines
• MOA-
• Release calcium from sarcoplasmic reticulum in
skeletal muscles and cardiac muscles
• Inhibit phosphodiasterase which degrades cAMP.
• Block the adenosine receptors in airway muscles and
mast cells.
• Example- Theophylline
• Amoniphylline
• Doxophylline
9. Pharmacological actions
• CNS- Theophylline is CNS stimulant, it promotes the sense
of well being, alertness, overcome fatigue. It tends to
improve performance and increase motor activity.
• CVS- These directly stimulate heart and the force of
myocardial contractions. Tachycardia is very common with
theophylline but other caffiein generally lowers heart rate.
• Smooth Muscles- All smooth muscles are relaxed. The most
prominent effect is exerted on bronchi. Vital capacity is
increased.
• Kidney- these are mild diuretics. These inhibit the tubular
reabsorption.
• Skeletal Muscles- Enhances the contractile power of skeletal
muscles.
10. Anticholinergics
• These cause bronchodilation by blocking M3
receptors. They act primarily in larger airways
which receive vagal innervation.
• These are less efficatious than inhaled beta 2
sympatjimimetics.
• Examples- Ipratomium
Titropium
11. Leukotriene antagonist
• Leucotriene receptors cause bronchoconstriction,
stimulate mucus sense and increase capillary
permeability which leads to pulmonary edema.
• The antagonists block the receptors and cause
broncho dilatin in poorly respond asthamatic
patients.
• Examples- Montelukast, Zafirlukast, Zeleuton.
12. Mast Cell Stabilizers
• These are synthetic chromone derivative which
inhibit degranulation of mast cells by trigger
stimuli.
• Example- sod. Cromoglycate, ketotifen
13. Corticosteroids
• These are not bronchodilators. They act by
inhibiting inflammatory cytokine production and
eosinophilic, lymphocytic infiltration of lungs.
• They reduce bronchial hyperactivity, mucosal
edema and suppress inflammatory response to
AG:AB reactions.
• For example- prednisolone, hydrocortisone,
beclomethasone, budesonide, flunisonide.
14. Anti- IgE antibody
• It inhibit binding of IgE to mast cells.
• It inhibit binding of IgE to basophils.
• It inhibit activation of IgE to prevent mast cell
degranulation.
• Omalizumab is a recombimamt human monoclonal
antibody.
