Bronchial asthma pharmacology

Receptors

Pathogenesis
Allergic antigen
⬇
1st exposure
⬇
Antigen presenting cells presents it to Type 2 Helper (TH2)
⬇
Releases IL-4 —————Bcell Maturation————> IgE
⬇
IgE Fixed on mast cell
⬇
2nd exposure
⬇
Antigen bind to IgE bound to mast cell
⬇
Degranulation of mast cells
⬇
Histamine, cytokines (LT, PGs)
⬇
Causes bronchoconstriction

This is Type I hypersensitivity reaction i.e. exaggerated immune response

Classification
@BMCHEL

● Bronchodilators
○ Adrenergic agonists/ Sympathomimetics
■ Non selective ⇒ Adrenaline, Ephedrine, Isoprenaline
■ β-2 selective
■ Short acting ⇒ Salbutamol, Terbutaline
■ Long acting ⇒ Salmeterol, Formeterol, Bambuterol
○ Methylxanthines ⇒ Aminophylline, Theophylline, Etophylline,
Doxophylline
○ Anticholinergic ⇒ Ipratropium bromide, Tiotropium bromide
 ● Mast cell stabilizer ⇒ Sodium cromoglycate, Ketotifen
● Corticosteroid
○ Systemic
■ Hydrocortisone, Prednisolone, Dexamethasone,
Betamethasone
○ Inhalational
■ Budesonide, Beclomethasone dipropionate, Fluticasone
propionate
● Anti-Histaminics ⇒ Cetrizine, Loratidine
● Anti-IgE Ab ⇒ Omalizumab
● Leukotriene antagonist ⇒ Montelukast, Zafirlukast

Bronchodilators :-
1. Sympathomimetics

● MOA
○ bind to β2 receptor (Gs) in bronchi ⇒ AC stimulation ⇒(+)

ATP—>cAMP↑ ⇒ Relaxes smooth muscle of the airway ⇒

Bronchodilation

○ Also inhibits release of mediators from mast cells.

● ADR
○ Vasodilation & reflex tachycardia
○ Restlessness, Nervousness, Palpitation (PaRN)
○ Muscle tremor
○ Cardiac arrhythmia
● Salbutamol
○ Rapid onset of acion
○ Short duration of action
○ Less palpitation & rise in BP
○ Used to terminate & abort the attack of asthma
○ Route ⇒ apidly effective by pressurized MDI or puff or slow i.v. 0.25mg
○ Not suitable for wound the clock prophylaxis

● Salmeterol
○ Long acting >24hr
○ But slow onset
○ Formeterol used in nocturnal asthma due to quicker onset of action
(5 min)
2. Methylxanthines

● MOA
○ cAMP —-PDE—> AMP
○ Mrthylxanthines inhibit PDE
○ ↑cAMP
■ Inhibition of phosphodiesterase enzyme which is responsible
for degradation of cAMP or cGMP.
■ Hence, increase in cAMP causes bronchodilation due to
smooth muscle relaxation.
● ADR
○ Restlessness, Nervousness, Palpitation (PaRN)
○ ↑HR, Arrhythmia,
○ Headache, insomnia, seizure
○ ↑Muscle tone
■ This drug has narrow safety margin. So, its level should be
monitored in plasma.
● Interaction (Theophylline)
○ Enhances effect of ⇒ Sympathomimetics, Hypoglycemics
○ Decreases effect of ⇒ Lithium, phenytoin
○ CYP inhibitors increase its metabolism & plasma level ⇒ Cimetidine,
Allopurinol
○ CYP inducers decrease its metabolism & plasma level ⇒
Phenobarbitone, Rifampicin

3. Anticholinergics

● MOA
○ Binds to M3 receptor & prevent Ach from binding (Competitive
inhibition)
○ Cholinergic constrictor tone is blocked
○ Airways dilate
● ADR
○ Dilated pupil, blurring of near vision
○ Dry mouth
○ Difficulty in swallowing and talking
○ Dry, flushed & hot skin
○ Difficulty in micturation

Leukotriene antagonist
● MOA
○ Decrease the synthesis of Leukotrienes
○ Prevent LT from binding to cys-LT receptors
■ Prevents bronchoconstriction
■ ↓ Mucus secretion
■ ↓ vascular permeability ⇒ prevent inflammation
● ADR
○ Headache, Eosinophilia & Neuropathy (HEN)
○ Rashes
 ○ Few cases of Churg-Straws syndrome (Vasculitis with eosinophilia)

Mast cell stabilizer

● MOA

○ Antigen & IgE (Ab) reaction on mast cell membrane causes Ca++
influx

Mast cell stabilizer inhibits influx of Ca++

Inhibition of degranulation thus inhibits release of mediators

● ADR

○ Bronchospasm !!
○ Throat irritation, Cough
○ Headache, dizziness, rashes
● Why sodium cromoglycate used only for the prophylaxis of bronchial
asthma?

○ Preventative Action: Sodium cromoglycate prevents the release of

inflammatory chemicals, stopping asthma attacks before they start.
○ Safety Profile: It's safe for long-term use with minimal systemic side
effects.
○ Non-Steroidal: Unlike corticosteroids, it doesn't contain steroids,
making it a preferred option for those sensitive to them.
○ Suitable for Children and Pregnant Women: It's safe for use in these
populations, providing long-term asthma management.
○ Preventive Maintenance: Regular use helps maintain asthma control,
reducing the risk of flare-ups and complications.

Corticosteroids
● MOA

○ Inhibit the enzymes Phosphlipase A2 (precursor)

■ Thus decrease production of inflammatory mediators
○ Bind to glucocorticoid receptor (GR) in the cytoplasm
■ Regulate gene transcription ⇒ ↓synthesis of inflammatory
mediators
○ Increase responsiveness of bronchial smooth muscle to beta-2
agonists
● ADR

○ Inhalational

■ Pharyngeal irritation
■ Coughing
■ Dry mouth
■ Oropharyngeal candidiasis
 ■ Hoarseness
○ Systemic

@CUSHINGOID

■ C ⇒ Cataracts
■ U ⇒ Ulcer
■ S ⇒ Striae, Skin thin
■ H ⇒ Hypertension, Hirsutism
■ I ⇒ Immunosuppression ⇒ Increased infection
■ N
■ G ⇒ Glycosuria, Glaucoma
■ O ⇒ Obesity, Osteoporosis
■ I
■ D ⇒ Diabetes
● Inhaled steroid therapy

Peak after 4-7 days and persists for few weeks after discontinuation

● Advantage of using glucocorticoid by inhalation route

○ Localized Action: Inhaled glucocorticoids act directly on the airways,

targeting inflammation where it occurs, without significantly affecting
the rest of the body. This reduces the risk of systemic side effects
compared to oral or injectable forms of glucocorticoids.
○ Reduced Systemic Side Effects: Because the medication is delivered
directly to the lungs, lower doses can be used compared to oral
glucocorticoids, minimizing the risk of systemic side effects such as
adrenal suppression, osteoporosis, and growth retardation, which
are more common with systemic administration.
○ Improved Lung Function: Inhaled glucocorticoids effectively reduce
airway inflammation and improve lung function, including increased
airflow and reduced bronchial hyperresponsiveness, leading to
better control of asthma symptoms and fewer exacerbations.
○ Preventive Maintenance: Regular use of inhaled glucocorticoids as
part of a maintenance regimen helps to control underlying
inflammation, reducing the frequency and severity of asthma attacks
and the need for rescue medication.
○ Fast Onset of Action: Inhaled glucocorticoids have a rapid onset of
action, providing relief from asthma symptoms within hours to days
of starting treatment, making them suitable for both acute and
long-term management of asthma.
○ Flexible Dosing: Inhaled glucocorticoids allow for flexible dosing
based on the severity of asthma symptoms and individual patient
response, with the option to adjust doses as needed under the
guidance of a healthcare provider.
Anti IgE antibody
● MOA
○ Binds with IgE and prevent it from binding to mast cell ⇒ Inhibit
release of histamine
● ADR
○ Pain at injection site
○ Allergic reaction

Anti-histaminic Drugs (H1)

● MOA
○ Prevent histamine from binding to its receptors (???)
● ADR
○ Fatigue
○ Light headedness
○ Diminished concentration
○ Sedation
○ Tendency to fall asleep
○ Headache

Management of status asthmaticus

● Early treatment:
○ Nebulized: Salbutamol & ipratropium bromide
○ I.v. hydrocortisone hemisuccinate
○ Inhalation of high flow humidified oxygen
○ Correct dehydration
● If poor response seen in 1 hour then:
○ Hospitalize
○ Intubation & marked ventilation
○ 5% glucose in saline to correct dehydration
○ IV Sod.bicarbonate to correct acidosis
○ Repeat: Nebulized: Salbutamol & ipratropium bromide 30 min
○ IV: hydrocortisone 100-300mg every 4-6min.
○ Antibiotics for chest infection
○ Exclude pneumothorax (X-ray)