Drugs used in the management of COPD

Chronic Obstructive Pulmonary Disorder (COPD)

Objectives: you should be able to
 Describe the classes of drugs used in the management of COPD and their indications for
use.
 Explain mechanism of action and ADR.

Definition:
COPD is an abnormal inflammatory response of the respiratory tract to anxious with airflow imitation
which is not fully reversible. It is mostly in chronic smokers Chronic exposure to dust and respiratory
infection are other causative factors.

COPD includes
1) Chronic Bronchitis.
2) Emphysema.

Chronic bronchitis
Defined as a chronic productive cough for three months in each of two successive years in a patient in
whom other causes of chronic cough have been excluded.

Emphysema
Abnormal and permanent enlargement of the airspaces distal to the terminal bronchioles that is
accompanied by destruction of the airspace walls, without obvious fibrosis.

Drug therapy: Recommended drug therapy is summarized here.

Stage Recommended Treatment

All • Avoidance of risk factors (e.g., smoking).
• Influenza vaccine annually.
• Pneumococcal polysaccharide vaccine.
• Treatment of complications.
Mild COPD Short-acting bronchodilator when needed.
Moderate COPD • Regular treatment with one or more bronchodilator.
• Rehabilitation
Severe COPD • Regular treatment with one or more bronchodilator.
• Inhaled corticosteroids for patients with repeated exacerbation or
persistent symptoms despite bronchodilator therapy.
• Rehabilitation.
Very Severe COPD • Regular treatment with one or more bronchodilator.
• Inhaled corticosteroids if symptoms persist despite bronchodilator
therapy.
• Rehabilitation.
• Long term O2 therapy if chronic respiratory failure.
• Surgical treatments considered.
Symptoms of COPD

1
The characteristic symptoms of COPD are mainly chronic and progressive dyspnea, cough, and sputum
production that can be variable.

Dyspnea: Progressive, persistent and characteristically worse with exercise.

Chronic cough: May be intermittent and may be unproductive.

Chronic sputum production: COPD patients commonly cough along with sputum.

Management

Management of COPD is mainly based on the principles of

 Prevention of further progress of disease

 Preservation and enhancement of pulmonary functional capacity
 Avoidance of exacerbations in order to improve the quality of life.

Treatment

 Drugs used in asthma also help COPD but the response in not as good.
 Smoking should be stopped. For bronchospasm, inhalation of a B2 agonist or ipratropium is
needed.
 Tiotropium or long acting B2 agonists may be used for day-long bronchodilation.
 Patients with repeated exacerbation may require inhaled steroids for controlling the frequency
and severity of episodes.
 Theophylline may also relieve bronchospasm.
 Acute exacerbation needs a course of antibiotics as respiratory infections are common in these
patients.

2
 Drugs for COPD

Bronchodilators Glucocorticoids Combination therapy Others

1 β2 – agonists Anti-oxidants

Short acting: Mucolytics

Salbutamol & terbutaline

Long acting:

Salmeterol & formoterol

2 Anticholinergic agents

Ipratropium, Tiotropium

3 Methylxanthanes

Theophylline

1. Bronchodilators
Bronchodilators are central to the symptomatic management of COPD.

They mainly improve emptying of the lungs, reduce dynamic hyperinflation and improve exercise
performance.

 Drugs that expand pulmonary airways (bronchi)-bronchodilators-block the early response by

inhibiting immediate bronchoconstriction

 smooth muscle relaxation

 Some agents, especially theophylline and β2-adrenergic agonists, inhibit late response
inflammation

 Used when a persistent cough and bronchial constriction are present

 In addition to relaxing smooth muscles and reducing airway reactivity, bronchodilators reduce
coughing, wheezing, and shortness of breath

 Agents are usually given via inhalation, but some can be given orally or parenteral (intravenous,
intramuscular, or subcutaneous route)

 Most drugs have a rapid onset of action (within minutes), but the effect usually wanes in 5 to 7 hours

 Some agents, especially theophylline, inhibit the delayed response to antigen.

Three major classes of bronchodilators:

3
  β2 - agonists:

Short acting: salbutamol & terbutaline

Long acting : Salmeterol & formoterol

 Anticholinergic agents: Ipratropium, Tiotropium

 Methylxanthines: Theophylline (a weak bronchodilator, which may have some anti-inflammatory

properties).

 2-Agonists:
 β2-agonists are most widely prescribed sympathomimetic drugs
– because of their β2 selectivity, oral activity, and rapid onset and long duration of action (4
hours)
• Short acting: Salbutamol and terbutaline
• Longer acting: Salmeterol
 Inhalation route allows greatest local effects with fewest adverse effects
 Inhaled agents cause bronchodilation equal to isoproterenol and persists for 4 hours.
 Two new drugs, Salmeterol and formoterol, have a long duration of action and high lipid
solubility. Both drugs at high concentrations move slowly into airway smooth muscle, so effects
can last up to 12 hours.
 MOA of 2-Agonists: Binding of the agonist to the receptor results in change in the protein
structure, which enables interaction with intracellular G proteins, production of cAMP and then
protein kinase A, which mediates the bronchodilating effects via its action on smooth muscles.

2. Glucocorticoids

 Regular treatment with inhaled glucocorticoids is appropriate for symptomatic patients with an
FEV1<50%pred and repeated exacerbations.
 Chronic treatment with systemic glucocorticoids should be avoided because of an unfavorable
benefit-to-risk ratio.

4
3. COMBINATION THERAPY

Combination therapy of long acting ß2-agonists and inhaled corticosteroids show a significant additional
effect on pulmonary function and a reduction in symptoms. Mainly in patients with an FEV1<50%pred

4. Others

Mucolytics

Normally the respiratory mucus is watery. Glycoproteins in the mucus are linked by disulphide bonds to
form polymers making it slimy. In respiratory diseases, glycoproteins form larger polymers with plasma
proteins present in the exudate and the secretions become thick and viscid. Mucolytics liquefy sputum
making it less viscid so that it can be easily expectorated.

The following are mucolytics

Bromhexine: Bromhexine, a semisynthetic compound related to vasicine (an alkaloid from the plant
Adhatoda vasica) is a good mucolytic. It depolymerises the mucopolysaccharides in the mucus. It is given
orally 8-6 mg thrice daily. Side effects are minor – may cause rhinorrhoea and lacrimation.

Ambroxol: It is a metabolite of bromhexine with actions similar to it. Ambroxol may be given orally
or by inhalation. It can be used as a alternative to bromhexine. 15-30 mg TDS.

Acetylcysteine: Acetylcysteine opens disulfide bonds in mucoproteins of the sputum reducing its
viscosity. It is given by aerosol. Side effects are common and hence is not preferred

Carbocysteine: Carbocysteine is similar to acetylcysteine and is used orally. It can cause

gastrointestinal irritation and rashes. Dose 250-750 mg TOS MUCODYNE 350 mg cap, 250 mg/ml
syrup.

Pancreatic dornase: Deoxyribonucleotidetein is a major component of the purulent respiratory tract

secretions. Pancreatic dornase is a deoxyribonuclease obtained from the beef pancreas. It breaks the

5
deoxyribonucleic acid (DNA) into smaller parts thus making the secretions thin and less viscid. It is
administered by inhalation. Pancreatic dornase can cause allergic reactions.

New pharmacotherapies for COPD

1. New LAMA monotherapy

2. New LABA monotherapy

3. New LABA+LAMA combination therapy

4. New LABA+ICS combination therapy

5. New oral agents

Questions
 Classify the drugs used for the management of COPD with examples. Explain their
pharmacology
 Classify the drugs used for the management of COPD with examples. Write the pharmacology of
Bronchodilators.
 Define COPD. Explain the pharmacology of Theophylline.
 Discuss the mode of action, adverse effects and therapeutic applications of salbutamol.