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Bronchial Asthma 2.0
Bronchial Asthma 2.0
Asthma
1st exposure: Antigens (pollen, house dust mites) > Increased IgE circulating in
blood/ attached to mast cells.
Re-exposure : Resulting Ag-Ab reaction on the surface of lung mast cells >
Degranulation releasing spasmogens ( Hist, 5-HT, PGD₂, LTC₄, LTD₄)
LTC₄ and LTD₄ are strong bronchoconstrictors, primary components of SRS-A in
both early and late phases.
Early phase release > bronchoconstriction
Late phase release > Inflammation, pulmonary edema, mucous secretion, bronchial
hyperreactivity, epithelial damage.
SYMPTOMS
Dyspnoea, wheeze and non-productive cough with limitation of activity.
Reversible, worsens at night.
Tenacious Mucous production
SIGNS
Increased RR (use of accessory muscles).
Hyper resonant percussion note.
Rhonchi (Expiratory>>Inspiratory)
Severe attack: SILENT CHEST
In between attacks: No signs
Classification
• The National Asthma Education and Prevention Program has classified asthma as:
Intermittent:
Symptoms on ≤ 2 days a week. No interference with normal activities. Night time symptoms
occur on ≤ 2 days a month. Lung function tests are normal.
• Mild persistent:
Symptoms occur on ≥ 2 days a week but do not occur every day. Attacks interfere with daily
activities. Night time symptoms occur 3 to 4 times a month. Lung function tests are normal
when the person is not having an asthma attack.
• Moderate persistent:
Symptoms occur daily. Inhaled short-acting medication is used every day. Symptoms interfere
with daily activities. Night time symptoms occur ≥ 1 time every week, but do not happen every
day. Lung function tests are abnormal ( 60% to 80%), and PEF ≥ 30% from morning to
afternoon.
• Severe persistent:
Symptoms occur throughout each day with severe limitation of daily physical activities. Night
time symptoms occur often, sometimes every night. Lung function tests are abnormal (≤
60%), and PEF ≥ 30% from morning to afternoon.
Therapeutic approach
Prevention of Ag:Ab reaction: Avoidance of antigen,
hyposensitization
Neutralization of IgE: Omalizumab
Suppression of inflammation and bronchial hyperreactivity:
Corticosteroids
Prevention of release of mediators: Mast cell stabilizers
Antagonism of released mediators: LT antagonists,
antihistaminics, PAF antagonists
Blockade of constrictor neurotransmitters: Anticholinergics
Mimicking dilator neurotransmitters: Sympathomimetics
Directly acting bronchodilators: Methylxanthines
Pharmacotherapy
β₂ Adrenergic agonists
MoA
GPCR mediated ↑cAMP production > smooth muscle relaxation
↓release of mediators in mast cells
↓microvascular leakage and ↓bronchial muscular edema (after exposure of Hist, LTD₄, PGD₂)
↓Mucous secretion, ↑mucociliary clearance.
ADRs
Muscle tremor (β₂ on skeletal muscle)
Tachycardia (direct effect on atrial β₂, reflex effect from ↑peripheral vasodilation)
Hypokalemia (β₂ effect on skeletal muscle uptake of K+)
Restlessness
Hypoxaemia (↑ V/Q mismatch due to reversal of hypoxic pulmonary vasoconstriction)
Metabolic effects (↑FFA, Glucose, Lactate, insulin)
Methyl Xanthines
Pharmacodynamics
Nonspecific PDE inhibition and ↑cAMP and cGMP.
Adenosine receptor antagonism
HDAC activation > increases anti-inflammatory effects of corticosteroids.
ADRs
Headache, nausea, vomiting, gi discomfort, Diuresis, epileptic seizure, Cardiac arrhythmia.
Drug Interactions
Smoking, phenytoin, rifampicin, phenobarbitone enhance their metabolism.
Ciprofloxacin, erythromycin, cimetidine, allopurinol, ocp inhibit the metabolism.
Effects of Furosemide, sympathomimetics, digitalis, oral anticoagulants, hypoglycaemics are
enhanced.
Effects of phenytoin, lithium are decreased.
Anticholinergics
Competitive antagonism of Ach at muscarinic receptors (M3 and M1).
GPCR mediated bronchodilation and ↓mucous secretion.
Inhibitory effect on inflammatory mediators and vagal tone on smooth muscle.
Well tolerated, less systemic S/E.
Rebound ↑airway responsiveness, Viscous mucous production, bitter taste, dry
mouth, urinary retention.
Add-on therapy in patients not controlled with LABA. Less effective in acute
attacks.
Corticosteroids
ADRs
Inhalational:
Local: Dysphonia, oropharyngeal candidiasis,
cough
System :
Adrenal suppression and insufficiency, Growth
suppression, bruising, cataracts, osteoporosis
glaucoma, metabolic abnormalities (glucose,
insulin, TGs), psychiatric disturbances
(euphoria, depression), pneumonia
Systemic:
Steroid withdrawal syndrome, fluid retention,
↑appetite, osteoporosis, hypertension, peptic
ulcer, anaphylaxis
Others
• Cromones: Cromolyn Na stabilizes mast cells and inhibits inflammation.
• PDE-4 inhibitors: Roflumilast relaxes smooth muscle and inhibits inflammation by ↑cAMP.
Reduces eosinophil infiltration and allergen exposure.
• Antihistamines: 2nd generation antihistamines like Cetrizine, Azelastine have some
beneficial effects (unrelated to H1 receptors).
• Antileukotrienes: 5-LOX inhibitors (Zileuton) and LT antagonists (Montelukast, Zafirlukast,
Pranlukast) causes bronchodilation, improved lung functions.
Used in treatment of mild bronchial asthma, add on therapy in patients not controlled
with ICS, exercise induced asthma.
• Immunomodulators: Omalizumab (Anti-IgE receptor Antibody) used for treatment of
severe asthma.
Newer Drugs
Antioxidants and Mucolytics: Vit C, E, NAC
Cytokine modifiers: Mepolizumab (Anti IL-5), IL-3, 4 blockers, Anti TNF-
α agents.
Azithromycin as anti-inflammatory.
MAP kinase inhibitors: Losmapimod (p38 MAP kinase inhibitors)
inhibits TH2 synthesis.
Tyrosine kinase inhibitors (Masitinib)
Recent Guidelines
Reference
• 1. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13e | AccessMedicine | McGraw Hill
Medical [Internet]. [cited 2021 Jun 24]. Available from: https://accessmedicine.mhmedical.com/book.aspx?
bookID=2189
• 2. Sharma & Sharma’s principles of pharmacology (Book, 2017) [WorldCat.org] [Internet]. [cited 2021 Jun
24]. Available from:
https://www.worldcat.org/title/sharma-sharmas-principles-of-pharmacology/oclc/1048258267
• 4. Charriot J, Vachier I, Halimi L, Gamez A-S, Boissin C, Salama M, et al. Future treatment for asthma.
European Respiratory Review. 2016 Mar 1;25(139):77–92.
• 5. Kuprys-Lipinska I, Kolacinska-Flont M, Kuna P. New approach to intermittent and mild asthma therapy:
evolution or revolution in the GINA guidelines? Clinical and Translational Allergy. 2020 Jun 3;10(1):19.
• 6. Nicanthony. Practice-Changing: What’s new in 2020 for asthma? [Internet]. County EM. 2020 [cited 2021
Jun 24]. Available from: http://blog.clinicalmonster.com/2020/06/16/practice-changing-2020-asthma/
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