TOPIC : Pharmacotherapy of Asthma and COPD

PRESENTED BY: SNEHASIS JANA

DIVISION: PHARMACOLOGY, Batch- 2022-2023

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
MAULANA ABUL KALAM AZAD UNIVERSITY OF TECHNOLOGY, W.B.
 CONTENT:

•Introduction

•Risk factors and clinical features of asthma

•Pathophysiology of asthma

•Different types of allergic treaction

•Phases of asthma

•Treatment of asthma

•COPD pathogenesis

•Risk factor and clinicaL features of COPD

•Treatment of COPD

•Future prospective of Asthma and COPD pharmacotherapeutics

  Introduction:

•Asthma: It is defined as chronic inflammation disease of airway that is

characterized by increasing responsiveness and reversible airway obstruction.

•COPD: An inflammatory disease of the both airways and lungs characterized

by alveolar destruction and bronchiolar fibrosis and also lead to loss of
bronchiolar elasticity which further leads to closer smaller air tubes during
expiration.
 Risk factors and clinical features for Asthma:
Risk factors for Asthma

Endogenous factors Environmental factors Wheezing

Heredity Indoor allergens

Tightness in
Obesity Outdoor allergens Breathlessness
the chest
Clinical
Respiratory track Infection Passive smoking Features

Over exercise Drugs like-aspirin

Coughing-
Increased
especially at
mucus
stress night or early
production
morning
 Pathophysiology of Asthma:
  Different types of allergic reactions:
Allergic reactions are exaggerated sensitivities (hypersensitive reactions) that occur when our
immune system responds abnormally to common substances called allergens such as pollen,
dust and certain foods.

Type I or anaphylactic reactions:

Mediated by proteins called IgE antibodies which are produced by the immune system.
These are produced in response to the allergens such as pollen, animal dander or dust mites, or
even certain foods.
This causes the release of histamine and other chemicals causing inflammation and swelling.

Examples : 
bronchial asthma, allergic rhinitis,  allergic dermatitis, food allergies, allergic conjunctivitis
anaphylaxis (allergic shock). 
  Cont’d:
Type II or cytotoxic reactions:
Mediated by proteins called IgG and IgM antibodies.
The antibodies involved in type II reaction damage cells by activating a component of
immunity

Example:
autoimmune hemolytic anemia,  immune thrombocytopenia.

Type III or immunocomplex reactions:

Also mediated by proteins i.e. IgM and IgG antibodies. These antibodies react with the allergen to
form immunocomplexes (antigen-antibody complexes). These complexes are responsible for the
allergic reaction.
Example:
serum sickness and  Arthus reaction
 Cont’d:
Type IV or cell-mediated reactions:

Type IV allergic reactions are also called the delayed type of hypersensitivity or
allergic reactions as they occur after at least 24 hours of exposure to the allergen.
 These reactions typically take 48-72 hours or longer to appear after contact with the
allergen.

Examples:
Many long-term infectious diseases, such as tuberculosis and fungal infections
 Phases of Asthma:
In the early phase reaction, allergen exposure
results in mast cell degranulation and the release of
mediators such as histamine
In the late phase reaction, the release
of cytokines and chemokines from mast
cells leads to recruitment of
inflammatory cells such as basophils,
lymphocytes and eosinophils
  Treatment of Asthma:
Subclass Mechanism of Action Effects Clinical Applications Pharmacokinetics,
Toxicities
1. BETA AGONISTS
Prompt, efficacious Asthma, chronic obstructive Aerosol inhalation. Duration
Albuterol Selective β2 agonist bronchodilation pulmonary disease(COPD). several hours. Also available
for nebulizer and parenteral
• drug of choice in acute use.
asthmatic bronchospasm  Toxicity: Tremor,
tachycardia.
 Overdose: arrhythmias

Slow onset, primarily Aerosol inhalation. Duration

Salmeterol Selective β2 agonist preventive action; potentiates Asthma prophylaxis 12-24 h.
corticosteroid effects.  Toxicity: Tremor,
tachycardia.
 Overdose: arrhythmias

Bronchodilation plus all other Anaphylaxis, asthma, others . Aerosol, nebulizer, or

Epinephrine Nonselective α and β agonist sympathomimetic effects on Rarely used for asthma (β2- parenteral
cardiovascular and other organ selective agents preferred)
systems.

Bronchodilation plus powerful Asthma, but β2-selective Aerosol, nebulizer, or

Isoproterenol β1 and β2 agonist cardiovascular effects. agents preferred parenteral
  Cont’d:
Subclass Mechanism of Action Effects Clinical Applications Pharmacokinetics,
Toxicities

2. 1. CORTICOSTEROIDS, INHALED

Fluticasone Alters gene expression Reduces mediators of
inflammation. Powerful
prophylaxis of exacerbations
Asthma. Adjunct in COPD Aerosol. Duration hours.
 Toxicity: Limited by
aerosol application
 Candidal infection, vocal
cord changes

2.2. CORTICOSTEROIDS, SYSTEMIC

Prednisone Like fluticasone Like fluticasone Asthma. Adjunct in COPD Oral. Duration 12-24 hours
 Toxicity: Multiple
  Cont’d:
Subclass Mechanism of Action Effects Clinical Applications Pharmacokinetics,
Toxicities

3. STABILIZERS OF MAST AND OTHER CELLS

Cromolyn, nedocromil Alters functions of delayed Prevents acute bronchospasm Asthma(other routes used for Aerosol. Duration 6-8 h
chloride channel. Inhibits ocular, nasal, and • Toxicity: Cough.
inflammatory cell activation gastrointestinal allergy) • Not absorbed so other
toxicities are minimal

4. METHYLXANTHINES

Theophylline Uncertain. Phosphodiesterase Bronchodilation, cardiac Asthma, COPD Oral. Duration 8-12 h but
inhibition. Adenosine receptor stimulation, increased skeletal extended-release preparations
antagonist muscle strength(diaphragm) often used.
• Toxicity: Multiple
  Cont’d:
Subclass Mechanism of Action Effects Clinical Applications Pharmacokinetics,
Toxicities

5. LEUKOTRIENE ANTAGONISTS

Montelukast, zafirlukast Block leukotriene D4 Block airway response to Prophylaxis of asthma, Oral. Duration hours.
receptors exercise and antigen especially in children and • Toxicity: Minimal
challenge in aspirin-induced asthma

6. IgE ANTIBODY

Omalizumab Humanized IgE antibody Reduces frequency of Severe asthma Parenteral. Duration 2-4 d
reduces circulating IgE asthma exacerbations inadequately controlled by • Toxicity: Injection site
above agents reactions (anaphylaxis
extremely rare)
 Additional therapy:
Acupunture Therapy: it can inhibits the allergic reactions, and the patient’s bronchial
smooth muscle tone is reduced and finally achieve anti-asthmatic process.

Helminth Therapy: Helminth infection is often accompanied by high levels of IgE

antibodies, and most antibodies are allergen specific and enhance tolerance of mast cell to
allergens.

Expectorant: This type of substance help to break the thick mucus. E.g Guaifensin

Aroma therapy: Sometimes taking the odors of essential oils contain volatile
Compounds may give freshness and sometimes small relief from bronchospasm.

Homeopathy: it can provide mild benefits against asthma. E.g Arsenic, Natrum etc.

Yoga, Pranayam, breathing exercise also help to improve the condition of asthma
patients.
COPD
 Risk factors and clinical features for COPD:
Risk factors for COPD

Environmental factor Predisposing factor Wheezing

Smoking, Air pollution, Genetics factors, female gender

Biomass smoke exposure Shortness Prolong
of expiratory
breathing Clinical time
Lungs conditions Features

Airway hyper-responsiveness, Asthma, Chronic mucus hyper- Chronic

Frequent
secretion, Recurrent Bronchopulmonary infection cough &
respiratory
increased
infection
sputam
  Treatment of COPD:

1. Beta agonist bronchodialator

2. Muscarinic antagonists
3. Leukotriene antagonist
4. Antiptotease
5. Transforming Growth Factor inhibitors
6. Peroxisome proliferator-activated receptor activators
7. PDE-4 inhibitors
8. Antibiotics therapy

The beta agonist, muscarinic antagonsit, leukotriene antagonist are already discussed at the time of
asthma.
4. Antiprotease:
Several proteases are implicated in COPD. In COPD there is an imbalance between protease
that digeset elastin protein. Antiprotease prevent the action of proteolytic enzyme and
found to be beneficial for prevention of progression of emphysemia(a lungs condition cause
shortness of breathing)

Example: α 1 antitrypsin, secretory leukoprotease inhibitors

5. Transforming Growth Factor inhibitors:

Play a key role in the fibrosis of small airways, which is turning out to be a major mechanism
for the progressive loss of FEV1 and may be activated by oxidative stress, smoking etc.
TGF- related gene show increased expression and shows their effects in small airways of COPD
patients.

Example: Resveratol( target the TGF-β)

6. Peroxisome proliferator- Activated receptor activation:
The activation of PPAR- & PPAR have the anti-inflammatory and immuno-modulatory action.
So the PPAR agonist inhibit the relaese of inflammatory cytokines from the monocytes and
lymphocytes.

Example: Rosiglitazone, Troglitazone

7. PDE4 inhibitors:
PDE-4 hydrolyse cAMP in the inflammatory cell. By inhibiting the PDE-4, intracellular cAMP
concentyration will be increase which leads to actiation of PKA, and phosphorylation, which
ultimayely results results in reduction of cellular inflammatory activity.

Example: Cilomilast, Roflumilast

8. Antibiotics therapy:

Disease condition Oral treatment Iv treatment

Mild exacerbation: no risk factors for poor Amoxicillin, Doxycycline, -
outcomes Azithromycin

Moderate exacerbation: with risk factors for Amoxicillin-clavulanate, Ampicillin-sulbactum,

poor outcomes levofloxacin, moxifloxacin. levofloxacin , moxifloxacin, 3rd
generation ceohalosporin

Severe excerbation with risk factor for Ciprofloxacin, levofloxacin Ciprofloxacin, levofloxacin(high
pseudomonus aeruginosa dose), betalactum
 Future prospective for the Asthma & COPD
pharmacotherapeutics:
There is a lots of available therapies for the asthma and COPD which I’ve described in this
presentation. But there is also developing new strategies for the treatment of asthma and COPD
like oligoneucleotide antisense therapy.

There is a novel treatment approach found to be vary much effective and safe which is inhaled PI
3Kδ inhibitors.
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•Louie S, Zeki AA, Schivo M, Chan AL, Yoneda KY, Avdalovic M, Morrissey BM, Albertson TE.
The asthma–chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic
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•Kankaanranta H, Harju T, Kilpeläinen M, Mazur W, Lehto JT, Katajisto M, Peisa T,

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Thank
You