Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is usually progressive and not fully reversible. It includes conditions such as chronic bronchitis and emphysema. The major risk factor is a history of cigarette smoking. Symptoms include cough, sputum production, and dyspnea. Diagnosis is made based on spirometry results showing an FEV1/FVC ratio of less than 70% post-bronchodilator. Treatment focuses on bronchodilators, inhaled corticosteroids, pulmonary rehabilitation, and managing exacerbations.

1. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
SHAHANAS CK
FIRST YEAR M.PHARM
PHARMACY PRACTICE
6/29/2016 1

2. DEFINITION
Global initiative for chronic obstructive lung
diseases defines COPD as:
“Disease characterized by airflow limitation
that is not fully reversible, usually progressive
and associated with abnormal inflammatory
response of the lungs to noxious particles or
gases.”
Common conditions associated with COPD are:
• Chronic bronchitis
• Emphysema
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3. CHRONIC BRONCHITIS:
Chronic bronchitis is associated with chronic or
recurrent excessive mucus secretion in to the
bronchial tree with cough that is present on most
days for at least 2 consecutive years in a patient, in
whom other causes of chronic cough have been
excluded.
EMPHYSEMA:
Abnormal permanent enlargement of airspaces
distal to the terminal bronchioles accompanied by
destruction of their walls without obvious fibrosis.
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4. EPIDEMIOLOGY
It is the 6th leading cause of death in the world.
Mortality rate is higher in males than females, and
in whites than blacks.
COPD is the 2nd leading cause of disability in the
united states.
In India prevalence rate indicates that about 5%
male and 2.7% female over the age of 30 suffer
from COPD.
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5. RISK FACTORS
Major risk factor for COPD development is a
history of cigarette smoking.
Environmental factors Host factors
•Tobacco smoke
•Occupational exposure
•Air pollution
•Serious respiratory disease
•Recurrent broncho-
pulmonary infection.
•Genetic predisposition
(α1- antitrypsin)
•Airway hyper-
responsiveness
•Impaired lung growth
•Gender
•Age
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6. PATHOGENESIS
Exposure to noxious chemical & gases – ↑sed
bronchial reactivity – inflammation
Chronic inflammation - remodeling & narrowing of
airway lumen- fixed / irriversible airflow
obstruction
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7. Four areas of lungs are affected:
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Central airways
• Inflammatory
exudates - ↑sed
number & size of
goblet cells &
mucus glands –
mucus
hypersecretion
• Airway cilia
destroyed - ↓sed
clearance of
mucus.
Peripheral
airways
• Thickenin
g of
smooth
muscles
&
connectiv
e tissues.
Lung
parenchyma
• Air spaces
enlarged,
attachmen
ts lost –
alveolar
collapse.
Pulmonary
vasculature
• Thickenin
g of
pulmonar
y vessels

8. 
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• Neutrophils
• CD8+ lymphocytes
• Macrophages
Prominent
cells of
inflammation:
• Tumor necrosis factor- α
• Interleukin – 8
• Leukotriene –B4
Inflammatory
mediators
involved:

9. Balance in antiprotease (protective) and
protease (aggressive) activity in the lungs is
disturbed in COPD – injury and damage to
normal lung tissue.
Noxious chemicals and gases increases
oxidative stress – stimulate inflammatory cells
to release additional proteases.
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10. PATHOPHYSIOLOGY
Pathologic changes in COPD are exhibited as:
Air flow limitation
Reduced ratio of FEV1 to FVC
Increased functional residual capacity due to air
trapping and thoracic hyper inflation.
Mucus plugging, chronic airflow limitation and
thoracic hyper inflation disturb normal ventilatory
dynamics.
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11. 6/29/2016 11
• Abnormality of gas
exchange: Changes in
pulmonary vasculature
• Pulmonary hypertension:
Elevated mean
pulmonary artery
pressure and pulmonary
vascular resistance
• Hypertrophy of right
ventricle: Development
of cor pulmonale.
Consequences
of advanced
disease

12.  Mucus plugging – colonization of
bacteria – contribute to chronic
inflammation.
 Factors contributes to airflow
obstruction.
 Increased mucus
 Airway wall fibrosis
 Alveolar collapse
 Normal elastic recoil of lung
during exhalation is lost in COPD-
patient use abdominal and chest
muscle to force air out- further
collapse of airways & air trapping
– thoracic hyper inflation6/29/2016 12

13. EXACERBATION
A change in patient’s baseline symptoms
(dyspnoea, cough, sputum production) beyond
day to day variability sufficient to warrant a
change in management.
Eosinophils are prominent during
exacerbation.
Typically have an infectious etiology, either
bacterial or viral.
‘haemophylus influenzae’, ‘streptococcus
pneumoniae’, ‘moraxella catarrhalis’ etc are
responsible for most of bacterial respiratory
infections.6/29/2016 13

14. CLINICAL PRESENTATION
SYMPTOMS
 Cough
 Sputum production
 Dyspnea
PHYSICAL EXAMINATION
 Cyanosis of mucosal membrane
 Barrel chest
 Increased resting respiratory rate
 Shallow breathing
 Pursed lips during expiration
 Use of accessory respiratory
muscles
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15. DIAGNOSTIC TEST RESULTS:-
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• Post bronchodilator FEV1/FVC < 70% -
COPD.
Spirometry
• Identifies thoracic hyper inflation, barrel
chest, and increased bronchovascular
markings.
Chest X-ray
• To exclude asthma if there is a doubt about
diagnosis.
Serial domiciliary peak
flow measurements
• Particularly with early onset disease or a
minimal smoking/family history
α1-Antitrypsin
• To identify organism if persistantly present
and purulent .
Sputum culture
• To reveal right ventricular hypertrophy and
changes consistent with cor pulmonale
ECG

16. Severity classification of COPD
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Severity stage Classification Predicted FEV1
1 Mild ≥80%
2 Moderate ≥50% & <80%
3 Severe ≥30% & < 50%
4 Very severe <30% or < 50%
with respiratory
failure

17. TREATMENT
Treatment objectives endorsed by GOLD:
Prevent disease progression
Relieve symptoms and improve exercise tolerance
Improve health status
Prevent and treat exacerbations
Reduce mortality
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18. THERAPEUTIC PLAN
1. Approaches to treatment
a) Pharmacotherapy
b) Non pharmacologic approach
c) Surgical management
d) Managing exacerbations
2. Improving outcomes
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19. a) PHARMACOTHERAPY
International guidelines recommend a stepwise
approach to pharmacotherapy based on disease
severity.
Patients with intermittent symptoms- treated with
short acting bronchodilators
Persistent symptoms – initiate long acting
bronchodilators
Patient with FEV1 < 50%, with frequent exacerbation
– inhaled corticosteroids
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20. In pharmacotherapy, inhaled route of
administration is preferred because it is more
efficacious and safer than available oral
therapies.
Inhaled therapy can be delivered by metered
dose inhaler (MDI), Dry powder inhaler (DPI) or a
nebulizer
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21. Continue previous therapies; initiate therapeutic trial with inhaled corticosteroids at
moderate – high dose.
Continue previous therapies. Initiate therapeutic trial of oral SR theophylline, titrate
to 8/12 mcg/ml
Symptoms persists, patient experiences frequent exacerbations .
If not previously done initiate and titrate inhaled anti cholinergics to 6 puffs QID
Combination
:scheduled long
acting inhaled β2
agonist & PRN short
acting inhaled β2
agonist
Combination: scheduled
short acting inhaled β2
agonist +inhaled
anticholinergic& continue
PRN short acting inhaled
β2 agonist
Combination: scheduled long
acting inhaled β2 agonist +
inhaled anticholinergic &
continue PRN short acting
inhaled β2 agonist.
Change initial therapy to scheduled basis and continue / initiate PRN inhaled β2
agonist
Initiate therapy with PRN short acting inhaled β2 agonist/ PRN inhaled
anticholinergic.
Patient with intermittent symptoms of COPD

22. I. BRONCHODILATORS
 Bronchodilators used for treating COPD includes:-
Short and Long acting inhaled β2 agonist
Short and Long acting inhaled anticholinergics
Methylxanthines
i. ANTICHOLINERGICS
 Ipratropium bromide
 Tiotropium bromide
 MOA
 blocks Ach – ↓ses cyclic GMP – privent bronchial
smooth muscle contraction.
 Reduce sputum volume.6/29/2016 22

23. 6/29/2016 23
Ipratropium
Initial MDI dosing – 40μg (2 inhalations)
QID
Dosing can be ↑sed to – 4 inhalations
QID
Administered through MDI with or
without spacer
Ipratropium bromide solution: dosing
500μg /2.5mL or more via nebulizer QID.
It has a slower onset of action, and effect
last for about 4-6 hours.
Patient complaints
Dry mouth
Nausea
Occasional metallic taste
Tiotropium
• It should be administered once
daily only via a handihaler
device , which delivers 10 μg of
tiotropium.
• Patient should not be placed
on both ipratropium and
tiotropium due to increased
risk of anticholinergic side
effects.
• It has a slower onset of action
within 30 minutes, with a peak
effect in 3 hours and persists
for about 24 hours

24. ii. β 2 AGONISTS
Indication
Used as first line bronchodilator or in conjunction
with anticholinergic agents in the maintenance
treatment of COPD.
Mechanism
Stimulate adenelyl cyclase – increased formation
of cyclic AMP – bronchial smooth muscle
relaxation.
Increases mucociliary clearance by increasing
ciliary activity.
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25. Administration and dosage
Normally administered via inhalation (DPI,MDI
with or without spacer, nebulizer) , if the
patient is unable to use inhalational devices
properly, oral agent is used cautiously
Agents with same duration of action should not
be used in combination.
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26. Short acting agents
Salbutamol
• Available dosage
forms:100, 200μg MDI&
DPI, 5mg/mL solution for
inhalation, 5mg pill &
0.24%syrup
• Duration of action: 4 – 6
hours
Terbutalin
• Avalable dosage forms:
400, 500 μg MDI & DPI &
2.5, 5 mg pills
• Duration of action : 4 – 6
hours
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27. Long acting agents
• Available dosage forms :
4.5, 12 μg MDI & DPI
• Duration of action: 12
hours
Salmeterol
• Available dosage forms :
25, 50 μg MDI & DPI
• Duration of action: 12 hoursFormoterol
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28. iii.METHYLXANTHINES
THEOPHYLLINE
 Theophylline compounds added to the drug regimen after
an unsuccessful trial of ipratropium bromide and β
adrenergics.
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• Inhibition of phosphodiesterase –
increase cyclic AMP level
• Inhibition of calcium influx in to smooth
muscle.
• Prostaglandin antagonism
• Stimulation of endogenous
catecholamines
• Adenosine receptor antagonism
• Inhibition of release of mediators from
mast cells and leukocytes
Mechanism
of action
It produce
bronchodilatio
n through:-

29. It also Increases
– mucociliary clearance
– stimulate respiratory drive
– enhance diaphragmatic contractility
– Improves ventricular ejection fraction
– stimulate renal diuresis.
ADMINISTRATION AND DOSAGE
It is available as 100 – 600mg pills, having variable
duration of action up to 24 hours.
a trial of 1-2 months with serum concentration
maintained at 5-12μg/mL and maximized.
Sustained release oral preparations are
appropriate for long term management of COPD.
6/29/2016 29

30. iv. CORTICOSTEROIDS
INDICATION:
Systemic corticosteroids: oral – for acute COPD
exacerbations
Inhaled corticosteroids: given alone and in
combination with long acting β2 agonist.
Mechanism of action
Reduce capillary permeability – reduce mucus.
Inhibit release of proteolytic enzymes from
leukocytes
Inhibit prostaglandins
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31. Agents used:
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systemic
• Prednisone: available as 5 – 60mg pills
• Methyl prednisolone: available as 4, 8 ,16 mg
pills
Inhaled
• Beclomethasone:50-400μg (MDI & DPI), 0.2-0.4 mg/ml
(solution for inhalation)
• Budesonide: 100, 200, 400μg (DPI), 0.20, 0.25, 0.5 mg/ml
soln for inhalation
• Fluticasone: 50-500μg (MDI & DPI)
Combinati
on with
long
acting β2
agonist
• Formoterol/beclometasone: 6/100 μg(MDI)
• Formoterol/budesonide: 4.5/160 μg (MDI), 9/320μg (DPI)
• Formoterol/mometasone:10/200, 10/400 μg (MDI)
• Salmeterol/Fluticasone: 50/100, 250, 500 μg(DPI)

32. Long term adverse effect:
Osteoporosis
Muscular atrophy
Thinning of skin
Development of cataracts
Adrenal suppression.
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33. v. α1 ANTITRYPSIN REPLACEMENT THERAPY
Used as an augmentation therapy in patient
with inherited AAT deficiency.
To maintain the serum concentrations above
the protective threshold.
Consists of weekly infusion of pooled human
AAT to maintain AAT plasma level greater than
10 micromolars.
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34. vi. ANTIBIOTICS
Indication: Used to treat exacerbation with
suspected infections.
Agents used for therapy include:
 2nd generation cephalosporins : cefuroxime, cefaclor
 Clotrimoxazole : trimethoprim + sulfamethoxazole
 β lactam with or without β lactamase inhibitor :
amoxicillin, amoxicillin – clavulanate
 Macrolides : azithromycin
 Ketolides : telithromycin
 Oral fluoroquinolone : ciprofloxacin, gatifloxacin
COPD exacerbations are treated for 3 – 10 days,
depending on the agent used and the patient.6/29/2016 34

35. vii.PHOSPHODIESTERASE 4 INHIBITORS
The principal action of phosphodiesterase-4
inhibitors is to reduce inflammation by inhibiting
the breakdown of intracellular cyclic AMP.
Roflumilast
 It is a once daily oral medication with no direct
bronchodilator activity, although it has been
shown to improve FEV1in patients treated with
salmeterol or tiotropium.
Dose: Roflumilast - 500 mcg (Pill)
6/29/2016 35

36. Adverse effects.
Phosphodiesterase-4 inhibitors have more
adverse effects than inhaled medications for
COPD
The most frequent adverse effects are
 nausea,
 reduced appetite,
 abdominal pain,
 diarrhea,
 sleep disturbances
 headache
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37. 6/29/2016 37
MUCOLYTICS
• Improve sputum
clearance and
disrupt mucus plugs
• Eg :- Iodinated
glycerol
EXPECTORANTS
• Guaifenesin may
be used
ANTIOXIDANTS
• N- acetyl cysteine
may reduce
exacerbation
frequency

38. b) NON PHARMACOLOGICAL THERAPY
1. TOBACCO CESSATION STRATEGIES.
 The 5 ‘A’ system is commonly used to evaluate
and assist smokers.
1. ASK : Use systematic approach to identify
tobacco users
2. ADVICE : Urge all tobacco users to quit
3. ASSESS : Determine willingness to make a
cessation attempt
4. ASSIST : Provide support for quit smoking
5. ARRANGE : Schedule follow up and monitor.
6/29/2016 38

39. Drugs for smoking cessation.
6/29/2016 39
AGENT USUAL DOSE DURATION COMMON
COMPLAINTS
Bupropion SR 150 mg OD- oral 12 weeks – 6
months
Insomnia, dry
mouth
Nicotine gum 2-4 mg gum
PRN
12 weeks Sore mouth,
dyspepsia
Nicotine inhaler 6-16 catridges
/day
Up to 6 months Sore mouth,
sore throat
Nicotine nasal
spray
8-40 doses / day 3 – 6 months Nasal irritation
Nicotine
patches
7 – 21 mg every
24 hours
Up to 8 weeks Skin reaction,
insomnia

40. 2. PULMONARY REHABILITATION
 Pulmonary rehabilitation program includes
 Patient education
 Exercise training
 Psychological support
 Nutritional therapy
Along with smoking cessation & optimal medical
treatment
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41. For the lungs to get more air
PURSED-LIP BREATHING
(like breathing out slowly into a
straw)
6/29/2016 41
INHALE EXHALE

42. 6/29/2016 42
Sit comfortably
&
relax your shoulders
Put one hand on your
abdomen. Now inhale
slowly through your
nose. (Push your
abdomen out while you
breathe in)
Then push in your
abdominal muscles
and breathe out using
the pursed-lip
technique
For the lungs to get more air
DIAPHRAGMATIC BREATHING

43. 3. IMMUNIZATIONS
 Annual influenza vaccination is recommended by
american thoracic society
 GOLD guidelines recommend pneumococcal
vaccine for all COPD patient with age 65 years
and older.
4. OXYGEN THERAPY
 Commonly used in two situations
 Acute exacerbation of COPD with drop in Pa O2 <
55mmHg.
 Patients who are chronically hypoxemic.
 Goal: correct arterial hypoxemia and prevent
secondary organ damage.6/29/2016 43

44. 5. CHEST PHYSIOTHERAPY.
 Loosens secretions, helps re expand the lungs,
increases efficacy of respiratory muscle use.
 Techniques used:-
 Deep breathing
 Coughing
 Postural drainage
 Chest percussion and vibration
6/29/2016 44

45. c) SURGICAL MANAGEMENT
BULLECTOMY
 Bullae are enlarged airspaces that do not
contribute to ventilation but occupy space in
the thorax, these areas may be surgically
excised – reduce obstruction – improve
functional lung volume
6/29/2016 45

46. LUNG VOLUME REDUCTION SURGERY.
It involves the removal of a portion of the diseased
lung parenchyma. this allows the functional tissue
to expand.
LUNG TRANSPLANTATION
Lung transplantation is an option in severe
emphysema and other options have failed.
Usually one lung is transplanted because the
survival rate has proved to be higher for people
with single-lung transplants than for people with
double-lung transplants6/29/2016 46

47. d) MANAGING EXACERBATIONS
General management of exacerbation include:
 Supplemental oxygen therapy
 Intensification of bronchodilator regimen
 Systemic corticosteroid therapy
 Antimicrobial therapy
 Ventilator support
6/29/2016 47

48. 6/29/2016 48
LEVEL 1
• Treated with
intensification of
bronchodilator therapy
– dosage of short acting
bronchodilator is
increased
• Administered either by
MDI or nebulizer
• Treatment also include
the use of systemic
corticosteroids
(prednisone )
LEVEL 2
• Treated on
an inpatient
basis,
treatment is
similar to
that of level
1
exacerbation
s
LEVEL 3
• Require
ventilator
support.
• Aggressive
bronchodilator
therapy is used
• Corticosteroid
therapy and
broad spectrum
antimicrobial
therapy may
used.

49. 2. IMPROVING OUTCOMES
i. PATIENT EDUCATION
 Counseling can help the patient to develop self
management skills, improve coping abilities and
improve overall health status.
 For inhalation therapies, the patient must
understand how to use the various delivery
devices correctly.
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50. REFERENCES
1) Appliedtherapeutics, theclinical useofdrugs:8th edition
byMaryAnneKodaKimbleetal;page:24.1–24.25.
2) Textbookoftherapeutics, druganddisease
management, 8th edition, byEricTHerfindaletal;
page:919–937
3) Pharmacotherapy apathophysiologicapproachby
Joseph.T.Dipiroetal;7th edition, pageNo:495–514.
4) www.medscape.com
5) GlobalInitiative forChronic Obstructive LungDisease:
Globalstrategyforthediagnosis, management, and
preventionofchronicobstructive pulmonary disease
updated2015.6/29/2016 50

51. 6/29/2016 51