Chronic Obstructive Pulmonary Disease (COPD)

Nadia Ghulam Hussain & Nida FatimaTrainee Pharmacists

AKUH, Karachi

Contents

• Definition• Epidemiology• Risk factors• Pathophysiology• Diagnosis• Management• Devices• References

COPD

• Also known as COLD (Chronic Obstructive Lung Disease ) COAD (Chronic Obstructive Airway Disease) Smoker’s lung CAL (Chronic Airflow Limitation) CORD (Chronic Obstructive Respiratory Disease)

Definition

Chronic obstructive pulmonary disease

(COPD) is a preventable and treatable disease

characterized by airflow limitation that is

progressive, not fully reversible and

associated with an abnormal inflammatory

response of the lungs.

Chronic Bronchitis

• Chronic bronchitis is a chronic inflammatory

condition in the lungs • It causes a cough that

often brings up mucus, as well as shortness of

breath,wheezing, and chest tightness

Emphysema

• In emphysema, there is over-inflation of the air sacs (alveoli) in the lungs, causing a decrease in lung function, and often, breathlessness. It involves destruction of the lungs.

Epidemiology

• More common in older people, especially those >65 years.

• Fifth leading cause of death and disability worldwide.

• Death rates for males and females are roughly equivalent.

• COPD mortality has also increased compared with heart and cerebrovascular disease over the same period.

Risk Factors

Exposures Host Factors

Environmental tobacco smoke

Genetic predisposition (AAT deficiency)

Occupational dusts and chemicals

Airway hyperresponsiveness

Air pollution Impaired lung growth

Risk Factors

• Exposures:– Cigarette smoking

(tobacco exposure) accounts for 85% to 90% of cases of COPD.

– Air pollution and occupational exposures result in inflammation and cell injury which leads to COPD.

Host Factors

• Host factor refers to the traits of an individual person that affect susceptibility to disease.– AAT deficiency accounts for less than 1% of COPD

cases.– Airway hyperresponsiveness due to various

inhaled particles may cause an accelerated decline in lung function.

– Impaired lung growth due to low birth weight, prematurity at birth, or childhood illnesses.

Pathophysiology of COPD

1. Airway inflammation2. Structural changes3. Mucociliary dysfunction

- Chronic inflammatory cascade for COPD

Diagnosis

1. Clinical presentation:– History – Physical examination

2. Diagnostic testing:– Pulmonary function testing– Laboratories– Imaging

Clinical Presentation

HistoryPhysical

Examination

- Symptoms: Cough, dyspnea, sputum, wheezing- Smoking history, environmental and occupational risk factors

- Cyanosis of mucosal membranes - Barrel chest - Increased resting respiratory rate - Shallow breathing - Pursed lips during expiration - Use of accessory respiratory muscles

Diagnostic Testing• Pulmonary function testing or

Spirometry– Comprehensive assessment of lung

volumes and capacities– Performed in all patients suspected

of COPD– FEV1 defines the severity of

expiratory airflow obstruction and is a predictor of mortality

• Bronchodilator reversibility:– A large increase in post-

bronchodilator FEV1 supports the diagnosis of asthma

Diagnostic Testing

• Laboratories:– ABG Monitoring: • Done for patients with severe COPD, respiratory failure

or a severe exacerbation

– ATT levels (1.5 - 3.5 gram / liter): • Measured in young patients who develop COPD and

have a strong family history. • A serum value <15–20% of the normal limits is highly

suggestive of α1-antitrypsin deficiency.

Diagnostic Testing

• Imaging:– Chest radiographs• Not sensitive for the diagnosis of COPD• Helpful in excluding other diseases (pneumonia, cancer,

congestive heart failure, pleural effusion & pneumothorax)

– Chest CT• For patients with severe COPD for lung volume

reduction surgery (LVRS) & lung transplantation.

COPD Management

• Goals of COPD Management:– To relieve symptoms– To improve quality of life– To decrease the frequency & severity of acute

attacks– To slow the progression of disease– To prolong survival

COPD Management

Nonpharmacologic Treatment

Smoking cessation

Immunization

Long term oxygen therapy

Pulmonary rehabilitation

Pharmacologic Treatment

Corticosteroids

Bronchodilators

AAT Replacement therapy

Smoking Cessation

• Only proven intervention to affect long term decline in FEV1 & slow the progression of COPD– Nicotine replacement therapy• Transdermal patch• Chewing gum• Inhaler• Nasal spray• Lozenges

– Non-nicotine pharmacotherapy• Bupropion• Varenicline

Smoking CessationProduct Side effects/Precautions

Nicotine replacement therapy Headache, insomnia, nightmares, nausea, dizziness, blurred vision

Bupropion Headache, insomnia, nausea, dizziness, xerostomia, hypertension, seizure.Avoid monoamine oxidase inhibitors

Varenicline Nausea, vomiting, headache, insomnia, abnormal dreamsWorsening of underlying psychiatric illness

Immunization

• Influenza vaccination– Reduces the incidence of influenza-related acute

respiratory illness in COPD patients– Patients with serious allergy to eggs should not be

given this vaccine.– Brand available: Fluarix® – An oral antiinfluenza agent (Oseltamivir) can be

given to such patients but its less effective and causes more side effects.

– Available brand: Tamiflu®

Immunization

• Polyvalent pnuemococcal vaccine– Recommended for all COPD patients• 65 years and older • Less than 65 years only if the FEV1 is less than 40%

predicted.

– Dosage: 0.5ml IM– Available brand: Pneumovax® (0.5ml pre-filled

syringes)

Long-term Oxygen Therapy

• Should be started if– Resting PaO2 is less than

55 mm Hg– Evidence of right-sided

heart failure, polycythemia, or impaired neuropsychiatric function with a PaO2 of less than 60 mm Hg

Pulmonary Rehabilitation

• Improves symptoms and quality of life

• Reduces frequency of exacerbations

• Components include:– Exercise training– Nutritional counselling– Psychosocial support

Pharmacologic Treatment

Bronchodilators

Long-acting

2-agonists

Anticholinergics

Methylxanthines

Short-acting

2-agonists

Anticholinergics

Short-acting 2-agonists•Stimula

te adenyl cyclase to increase the formation of cAMP which causes bronchodilation.

•Improve mucociliary clearance

MOA

•4 to 6 hours

Duration of action

•Albuterol (Ventolin®), levalbuterol, pirbuterol

Selective 2-agonists

•Metaproterenol, isoetharine, isoproterenol, epinephrine

Less selective 2-agonists

Short-acting Anticholinergics

•Competitively inhibit cholinergic receptors in bronchial smooth muscle, block Ach, with the net effect of reduction in cGMP, which normally constrict bronchial smooth muscle.

MOA

•4 to 6 hours, slower onset of action in comparison to -agonists

Duration of action

•Ipratropium (Atrovent®, Atem®)

•Atropine

Examples

Long-acting 2-agonists

•Same as that of short-acting 2-agonists

MOA•12

hoursDuration of action

•Salmeterol (Serevent®)

•Formoterol

•Arformoterol

Examples

Long-acting Anticholinergics

•Same as that of short-acting anticholinergics

MOA

•Cause bronchodilation within 30 minutes, which persists for 24 hours, allowing once daily dosing

Duration of action

•Tiotropium

Example

Combination Anticholinergics & 2-agonists

• Combining bronchodilators with different MOA allows reduced doses to be administored, reducing side effects.

• Albuterol and Ipratropium available as an MDI Combivent®

Methylxanthines•Produce bronchodilation

by:•Inhibition of PDE,

increasing cAMP levels•Inhibition of calcium ion

influx into smooth muscle

•Prostaglandin antagonism

•Stimulation of endogenous catecholamines

•Inhibition of release of mediators from mast cells and leukocytes

MOA

•8-12 mcg/ml

Therapeutic Serum Levels

Methylxanthines

• Minor side effects:– dyspepsia, nausea, vomiting, diarrhea, headache,

dizziness, tachycardia• Serious toxic effects: – arrhythmias and seizures

• Considered in patients who donot respond well to bronchodilators

Corticosteroids

• Mechanism of Action– Reduction in capillary permeability to decrease mucus– Inhibition of release of proteolytic enzymes from

leukocytes– Inhibition of prostaglandins

• ICS: Beclomethasone (Bekson, Clenil-A, Clenil Forte, Rinoclenil), flunisolide, budesonide, fluticasone, mometasone

• Systemic CS: Prednisolone (Deltacortil), Methylprednisolone, Prednisone

Corticosteroids

• Inhaled CS– Considered for symptomatic stage III or IV disease

who experience repeated exacerbation despite bronchodilator therapy

• Systemic CS– Short term use for acute exacerbations– Not used in chronic management because of high

risk of toxicity

Combination ICS & Bronchodilators

• Effective in reducing the rate of COPD exacerbations

• Reduces the number of total inhalations needed, more patient compliance

• Available combination:– Beclomethasone with salbutamol (Clenil

Compositum®)– Budesonide with formeterol– Fluticasone with salmeterol

AAT Replacement Therapy

• Considered for patients with AAT deficiency• Life time treatment• Therapy consists of giving a concentrated form

of AAT, derived from human plasma.• The recommended dosing regimen for

replacing AAT is 60 mg/kg administered IV once a week.

Indacaterol

• Indacaterol is an ultra-long-acting beta-adrenoceptor agonist

• Approved by FDA on July 1, 2011• Requires once daily dosing, unlike other long-

acting • In clinical trials, the most common adverse

events were runny nose, cough, sore throat, headache, and nausea.

• Recommended dose is one capsule (75mcg) per day.

Overview of Management

Devices used in COPD

• Inhalers • Small, handheld devices that deliver a puff of

medicine into the airways.• Metered-dose inhalers (MDIs) • Dry powder inhalers (DPIs) or breath

activated inhalers• Inhalers with spacer devices

Metered-dose Inhalers

• Contains a liquid medication delivered as an aerosol spray.

• Quick to use, small, and convenient to carry.

• Needs good co-ordination to press the canister, and breathe in fully at the same time

Breath-activated inhalersor DPI

• It releases a puff of dry powder instead of a liquid mist

• Require less co-ordination than the standard MDI.

• Slightly bigger than the standard MDI.

• Example: Rotahaler

Inhalers with spacer devices

• Spacer devices are used with pressurised MDIs

• The spacer between the inhaler and the mouth holds the drug like a reservoir when the inhaler is pressed.

Nebulizers• Nebulisers are

machines that turn the liquid medicines into a fine mist, like an aerosol.

• Useful in people who are very breathless e.g. In severe attack of COPD

• They are not portable

References

• BMJ Best Practices• American Thoracic Society COPD guidelines• The Washington’s manual of medical

therapeutics• Pharmacotherapy : A pathophysiologic

approach, Joseph T. DiPiro• Respiratory care pharmacology, Rau, Joseph