Drugs Acting on the Respiratory System

1
Drugs Acting on the Respiratory System
2
Introduction

• The respiratory system is subject to many
  disorders that interfere with respiration and
  other lung functions, including
• Respiratory tract infections
• Allergic disorders
• Inflammatory disorders
• Conditions that obstruct airflow (e.g. asthma and
  chronic obstructive pulmonary disease, COPD)

3
Introduction (Contd)

• Drugs that act on the respiratory system include
• Bronchodilators
• Corticosteroids
• Cromoglycates
• Leukotriene receptor antagonists
• Antihistamines
• Cough preparations
• Nasal decongestants

4
Introduction (Contd)

• Drugs acting on the respiratory system,
  especially for asthma, can be administered by
  inhalation, the advantages are
• Enhance therapeutic effects
• Minimize systemic effects
• Rapid relief of acute attacks

5

• Asthma is a chronic inflammatory disorder of the
  airways in which many cells and cellular elements
  play a role, in particular, mast cells,
  eosinophils, T lymphocytes, macrophages,
  neutrophils, and epithelial cells. In susceptible
  individuals, this inflammation causes recurrent
  episodes of wheezing, breathlessness, chest
  tightness, and coughing, particularly at night or
  in the early morning. These episodes are usually
  associated with widespread but variable airflow
  obstruction that is often reversible either
  spontaneously or with treatment. The inflammation
  also causes an associated increase in the
  existing bronchial hyperresponsiveness to a
  variety of stimuli.

6
The condition of a patients asthma may change
depending on the environment, activities, and
other factors. When the patient is well,
monitoring and treatment are still needed to
maintain control.
7
Introduction (Contd)

• There are various types of inhalation devices
• Metered-dose inhalers (MDIs)
• Pressurized devices that deliver a measured dose
  of drug with each activation
• With CFC or non-CFC propellant
• Hand-mouth coordination is required

8
Introduction (Contd)

• Spacers
• Use with MDIs
• Increase delivery of drug to the lungs decrease
  deposition of drug on the oropharyngeal mucosa
• Especially important for inhaled corticosteroids

9
Introduction (Contd)

• Dry-powder inhalers (DPIs)
• Include Turbuhalers Accuhalers
• Drugs are in the form of dry, micronized powder
• No propellant is employed
• Breath activated, much easier to use

10
Introduction (Contd)

• Nebulizers
• Small machine to convert a drug solution into
  mist
• Droplets in the mist are much finer than those
  produced by inhalers
• Through face mask or mouth piece held between the
  teeth
• Take several minutes to deliver the same amount
  of drug contained in 1 puff from an inhaler

11
Bronchodilators

• Drugs used to relieve bronchospasms associated
  with respiratory disorders
• Includes
• Adrenoceptor agonists
• Selective ß2-agonists other adrenoceptor
  agonists
• Antimuscarinic bronchodilators
• Xanthine derivatives

12
Bronchodilators (Contd)

• Adrenoceptor agonists
• (i) Selective beta2 agonists
• Stimulate beta2 receptors in smooth muscle of the
  lung, promoting bronchodilation, and thereby
  relieving bronchospasms
• They are divided into short-acting long acting
  types

13
Bronchodilators (Contd)
Short-acting ß-2 agonists
Drug Formulation Dosage Dosage
Adult Child
Salbutamol Oral tablet (C.R) 8 mg twice daily 4 mg twice daily
Salbutamol Inhaler (MDI), 100mcg/dose 100-200mcg up to three to four times daily Same as adult
Salbutamol Syrup, 2mg/5ml 4 mg three to four times daily 1-2 mg three to four times daily (2 yr)
Terbutaline Oral tablet (S.R) 5-7.5 mg two times daily -
Terbutaline Inhaler 500mg / dose ( Turbuhaler) 500 mcg up to four times daily -
Terbutaline Inhaler 250mg / dose (MDI) 250-500mcg up to 3-4 times daily Same as adult
14
Bronchodilators (Contd)
Long-acting ß-2 agonists
Drug Formulation Dosage Dosage
Adult Child
Formoterol Inhaler 4.5mcg / dose (Turbuhaer) 4.5-9 mcg once or twice daily Same as adult
Formoterol Inhaler 9mcg / dose (Turbuhaer) 4.5-9 mcg once or twice daily Same as adult
Salmeterol Inhaler 25mcg / dose (MDI) 50-100 mcg twice daily Same as adult
Salmeterol 50 mcg / dose (Accuhaler) 50 mcg twice Same as adult
15
Bronchodilators (Contd)

• Adverse effects
• Tachycardia and palpitations
• Headache
• Tremor

16
Bronchodilators (Contd)

• (ii) Other adrenoceptor agonists
• Less suitable less safe for use as
  bronchodilators because they are more likely to
  cause arrhythmias other side effects
• Ephedrine
• Adults 15-60 mg tid po
• Child 7.5-30 mg tid po
• Adrenaline (epinephrine) injection is used in the
  emergency treatment of acute allergic and
  anaphylactic reactions

17
Bronchodilators (Contd)

• Nursing Alerts
• When 2 or more puffs are needed, inform the
  patient that at least 1 minute should be allowed
  between puffs
• Inform the patient that salmeterol and
  formoterol, and oral ß-2 agonists should be taken
  on a fixed schedule, not on a prn basis
• Instruct the patient to report chest pain and
  changes in heart rhythm or rate, because ß-2
  agonists can cause cardiac stimulation
• Contact physician if symptoms such as
  nervousness, insomnia, restlessness and tremor
  become severe

18
Bronchodilators (Contd)

• Antimuscarinic bronchodilators
• Blocks the action of acetylcholine in bronchial
  smooth muscle, this reduces intracellular GMP, a
  bronchoconstrictive substance
• Used for maintenance therapy of
  bronchoconstriction associated with chronic
  bronchitis emphysema

19
Bronchodilators (Contd)
Drug Formulation Dosage Dosage
Adult Child
Ipratropium Inhaler 20 mcg / dose (MDI) 20-80 mcg three to four times a day 20-40 mcg three to four times a day (6yrs)
Tiotropium Inhaler 18 mcg /dose 18 mcg daily Not recommended in children and adolescents
20
Bronchodilators (Contd)

• Adverse effects
• Dry mouth
• Nausea
• Constipation
• Headache

21
Bronchodilators (Contd)

• Xanthine Derivatives
• Main xanthine used clinically is theophylline
• Theophylline is a bronchodilator which relaxes
  smooth muscle of the bronchi, it is used for
  reversible airway obstruction
• One proposed mechanism of action is that it acts
  by inhibiting phosphodiesterase, thereby
  increasing cAMP, leading to bronchodialtion

22
Bronchodilators (Contd)
Drug Formulation Dosage
Adult Child
Theophylline Tablet 200 / 300 mg (S.R.) 200 300 mg twice daily 10 mg / kg ((2yrs) twice daily
Capsule 50 / 100 mg (Slow release) 7-12 mg/ kg / day in two divided doses 10-16 mg / kg / day in two divided doses (916yrs) 13-20 mg / kg / day in two divided doses (30 months 8 yrs)
Syrup 80 mg / 15 ml 25 ml q6h 1 ml / kg (Max 25 ml) q6h (2yrs)
Aminophylline Injection 25 mg / ml 10 ml 500 mcg / kg / hr IV infusion, adjust when necessary 1 mg / kg /hr (6 months 9 years) 800 mcg / kg /hr (10 16 yrs) IV infusion, adjust when necessary
23
Bronchodilators (Contd)

• Adverse effects
• Toxicity is related to theophyline levels
  (usually 5-15 µg/ml)
• 20-25 µg/ml Nausea, vomiting, diarrhea,
  insomnia, restlessness
• gt30 µg/ml Serious adverse effects including
  dysrhythmias, convulsions, cardiovascular
  collapse which may result in death

24
Bronchodilators (Contd)

• Nursing alerts
• Plasma theophylline levels should be monitored to
  keep it in the therapeutic range, usually 5-15
  µg/ml. Dosage should be adjusted to keep
  theophylline levels below 20 µg/ml
• If patients miss a dose, the following dose
  should not be doubled

25
Bronchodilators (Contd)

• Nursing alerts (Contd)
• Instruct the patient that sustained-release
  formulations should be swallowed intact
• Caution patients in consuming caffeine
  containing-beverages and other sources of
  caffeine. Caffeine can intensify the adverse
  effects and decrease the metabolism of
  theophylline

26
Corticosteroids

• Used for prophylaxis of chronic asthma
• Suppressing inflammation
• Decrease synthesis release of inflammatory
  mediators
• Decrease infiltration activity of inflammatory
  cells
• Decrease edema of the airway mucosa
• Decrease airway mucus production
• Increase the number of bronchial beta2 receptors
  their responsiveness to beta2 agonists

27
Corticosteroids (Contd)
Drug Formulation Dosage Dosage
Adult Child
Beclomethasone Inhaler 50 mcg / dose (MDI) 200 mcg twice daily / 100mcg three to fours times daily Up to 800 mcg daily 50 100 mcg two to four times daily
Beclomethasone Inhaler 250 mcg / dose (MDI) 500 mcg twice daily / 250 mcg four times daily Not recommended
28
Corticosteroids (Contd)
Drug (Contd) Formulation Dosage
Adult Child
Budesonide Inhaler 50 mcg / dose (MDI) 200 mcg twice daily Up to 1.6 mg daily 50 400 mcg twice daily Up to 800 mcg daily
Budesonide Inhaler 200mcg / dose (MDI) 200 mcg twice daily Up to 1.6 mg daily 50 400 mcg twice daily Up to 800 mcg daily
Budesonide Inhaler 100 mcg / dose (Turbuhaler) 200-800 mcg once daily in evening Up to 1.6 mg daily in two divided doses 200-800 mcg daily in two divided doses / 200-400 mcg once daily in evening (lt12 yrs)
Budesonide Inhaler 200 mcg / dose (Turbuhaler) 200-800 mcg once daily in evening Up to 1.6 mg daily in two divided doses 200-800 mcg daily in two divided doses / 200-400 mcg once daily in evening (lt12 yrs)
Budesonide Inhaler 400 mcg / dose (Turbuhaler) 200-800 mcg once daily in evening Up to 1.6 mg daily in two divided doses 200-800 mcg daily in two divided doses / 200-400 mcg once daily in evening (lt12 yrs)
29
Corticosteroids (Contd)
Drug (Contd) Formulation Dosage Dosage
Adult Child
Fluticasone Inhaler 25mcg / dose (MDI) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 50 mcg / dose (MDI) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 125 mcg / dose (MDI) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 250 mcg / dose (MDI) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 50 mcg / dose (Accuhaler) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 100 mcg / dose (Accuhaler) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)
Fluticasone Inhaler 250 mcg / dose (Accuhaler) 100 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs)

• Acute attacks of asthma should be treated with
  short courses of oral corticosteroids, starting
  with a high dose for a few days

30
Corticosteroids (Contd)

• Adverse effects
• Inhaled corticosteroids
• Candidiasis of the mouth or throat
• Hoarseness
• Can slow growth in children
• Adrenal suppression may occur in long-term, high
  dose therapy
• Increases the risk of cataracts

31
Corticosteroids (Contd)

• Nursing alerts
• Rinse mouth with water without swallowing after
  administration to reduce the risk of candidiasis
• If taking bronchodilators by inhalation, use
  bronchodilators several minutes before the
  corticosteroid to enhance application of the
  corticosteroid into the bronchial tract

32
Combination Products

• May be appropriate for patients stabilised on
  individual components in the same proportion
• Muscarinic antagonistß2 agonist
• Combivent (20mcg Ipratropium 100mcg salbutamol
  /dose, MDI)
• Corticosteroidß2 agonist
• Symbicort (160mcg Budesonide4.5mcg Formoterol /
  dose, Turbuhaler)
• Seretide (SalmeterolFluticasone MDi in Lite,
  Medium, Forte preparation Accuhaler)

33
Cromoglycates

• Stabilise mast cells prevent the release of
  bronchoconstrictive inflammatory substances
  when mast cells are confronted with allergens
  other stimuli
• Only for prophylaxis of acute asthma attacks

34
Cromoglycates (Contd)
Drug Formulation Dosage Dosage
Adult Child
Cromoglycate Na Inhaler (1 mg 5mg/dose) 10 mg four times daily, may be increased to six to eight times daily Same as adult
Cromoglycate Na Nebuliser solution 10 mg / ml 2 ml 20 mg four times daily, may be increased six times daily Same as adult
Nedocromil Sodium Inhaler 2 mg / dose (MDI) 4 mg two to four times daily Sames as adult (gt6 yrs)
35
Cromoglycates (Contd)
Adverse effects Nursing Alerts
Transient Bronchospasm A selective ß2 agonist such as salbutamol or terbutaline may be inhaled a few minutes beforehand
Others coughing, throat irritation Others coughing, throat irritation
36
Cromoglycates (Contd)

• Nursing Alerts (Contd)
• Cromoglycates are for long-term prophylaxis,
  patients should administer on a regular schedule
  the full therapeutic effects may take several
  weeks to develop
• They are contraindicated in patients who are
  hypersensitive to the drugs

37
Leukotriene receptor antagonists

• Act by suppressing the effects of leukotrienes,
  compounds that promote bronchoconstriction as
  well as eosinophil infiltration, mucus
  productions, airway edema
• Help to prevent acute asthma attacks induced by
  allergens other stimuli
• Indicated for long-term treatment of asthma

38
Leukotriene receptor antagonists (Contd)

• Dosage
• Montelukast (5 10 mg tablets)
• Adult 10 mg daily at bedtime
• Child
• (2-5yrs) 4 mg daily at bedtime
• (6-14yrs) 5 mg daily at bedtime

39
Leukotriene receptor antagonists (Contd)

• Adverse effects
• GI disturbances
• Hypersensitivity reactions
• Restlessness headache
• Upper respiratory tract infection
• Manufacturer advises to avoid these drugs in
  pregnancy breast-feeding unless essential

40
Management of Chronic Asthma for adults
schoolchildren above 5yrs

• Step 1 Occasional relief short-acting
• beta2 agonist

• Step 2 Add regular preventer therapy
• Standard-dose inhaled corticosteroid

41
Management of Chronic Asthma for adults
schoolchildren above 5yrs (Contd)

• Step 3 Add long-acting inhaled beta2 agonist
• dose of inhaled corticosteroid may also be
  increased

• Step 4 Add high dose of inhaled corticosteroids

42
Management of Chronic Asthma for adults
schoolchildren above 5yrs (Contd)

• Step 5 Add regular oral corticosteroid
• E.g. prednisolone

43
Management of Chronic Asthma for adults
schoolchildren above 5yrs (Contd)

• Stepping down
• Review treatment every 3 months
• If symptoms controlled, may initiate stepwise
  reduction
• Lowest possible dose oral corticosteroid
• Gradual reduction of dose of inhaled
  corticosteroid to the lowest dose which controls
  asthma

44

• BREAK

45
Antihistamines

• H1 receptor antagonists
• Inhibit smooth muscle constriction in blood
  vessels respiratory GI tracts
• Decrease capillary permeability
• Decrease salivation tear formation
• Used for variety of allergic disorders to prevent
  or reverse target organ inflammation

46
Antihistamines (Contd)

• All antihistamines are of potential value in the
  treatment of nasal allergies, particularly
  seasonal allergic rhinitis (hay fever)
• Reduce rhinorrhoea sneezing but are usually
  less effective for nasal congestion
• Are also used topically in the eye, in the nose,
  on the skin

47
Antihistamines (Contd)

• First-generation H1 receptor antagonists
• Non-selective/sedating
• Bind to both central peripheral H1 receptors
• Usually cause CNS depression (drowsiness,
  sedation) but may cause CNS stimulation (anxiety,
  agitation), especially in children
• Also have substantial anticholinergic effects

48
Antihistamines (Contd)
Drug Dosage
Adult Child
Chorpheniramine (4 mg tablet, 2mg/ml Elixir expectorant) 4 mg q4-6hr, max 24 mg daily 1-2yrs 1 mg twice daily 2-12yrs 1- 2 mg q4-6h, Max12 mg daily
Hydroxyzine (25 mg tablet) 25 mg at night 25mg three to four times daily when necessary 6 months-6yrs 5-15 mg daily 50 mg daily in divided dose if needed gt6yrs 15-25 mg daily 50-100 mg daily in divided dose if needed
Diphendramine (10 mg/5ml Elixir) 25-50 mg q4-6h 6.25-25 mg q4-8 hr ( gt1 yr)
49
Antihistamines (Contd)
Drug (Contd) Dosage
Adult Child
Promethazine (10 25 mg tablets, 5mg/5ml Elixir) 25 mg at night 25 mg twice daily if needed 2-10yrs 5-25 mg daily in 1 to 2 divided dose
Azatadine (1 mg tablet) 1 mg twice daily 1-12 yrs 0.25-1 mg twice daily
50
Antihistamines (Contd)

• Adverse effects
• Sedation
• Dry mouth
• Blurred vision
• GI disturbances
• Headache
• Urinary retention
• Hydroxyzine is not recommended for pregnancy
  breast-feeding

51
Antihistamines (Contd)

• Second-generation H1 receptor antagonists
• Selective/non-sedating
• Cause less CNS depression because they are
  selective for peripheral H1 receptors do not
  cross blood-brain barrier
• Longer-acting compared to first-generation
  antihistamines

52
Antihistamines (Contd)
Drug Dosage
Adult Child
Acrivastine (Semprex) 8 mg three times daily Not recommended
Cetirizine (Zyrtec) 10 mg daily 5 mg daily / 2.5 mg twice daily (2-6 yrs)
Desloratadine (Aerius) 5 mg daily 1.25 mg daily (2-5 yrs) 2.5 mg daily (6-11yrs)
Fexofenadine (Telfast) 120-180 mg daily Not recommended
Loratadine (Clarityne) 10 mg daily 5 mg daily (2-5 yrs)
53
Antihistamines (Contd)

• Adverse effects
• May cause slight sedation
• Some antihistamines may interact with antifungal,
  e.g. ketoconazole antibiotics, e.g.
  erythromycin prokinetic drug-- cisapride or
  grapefruit juice, leading to potentially serious
  ECG changes e.g. Terfenadine

54
Cough preparations

• There are three classes of cough preparations
• Antitussives
• Expectorants
• Mucolytics

55
Cough preparations (Contd)

• Antitussives
• Drugs that suppress cough
• Some act within the CNS, some act peripherally
• Indicated in dry, hacking, nonproductive cough
  that interfere with rest sleep

56
Cough preparations (Contd)
Drug Dosage
Codeine phosphate 25mg/5ml syrup 15-30 mg three to four times daily
Pholcodine 5mg/5ml Elixir 5-10 mg three to four times daily
Dextromethorphan 10mg/5ml in Promethazine Compound Linctus 10-30 mg q4-8h
Diphenhydramine 10 mg/ 5ml 25 mg q4h, Max150 mg daily
57
Cough preparations (Contd)

• Adverse effects
• Drowsiness
• Respiratory depression (for opioid antitussives)
• Constipation (for opioid antitussives)
• Preparations containing codeine or similar
  analgesics are not generally recommended in
  children should be avoided altogether in those
  under 1 year of age

58
Cough preparations (Contd)

• Nursing Alerts
• Observe for excessive suppression of the cough
  reflex (inability to cough effectively when
  secretions are present). This is a potentially
  serious adverse effect because retained
  secretions may lead to lungs collapse, pneumonia,
  hypoxia, hypercarbia, and respiratory failure

59
Cough preparations (Contd)

• Expectorants
• Render the cough more productive by stimulating
  the flow of respiratory tract secretions
• Guaifenesin is most commonly used
• Available alone as an ingredient in many
  combination cough cold remedies

60
Cough preparations (Contd)

• Dosage
• Guaifenesin
• 100-400 mg q4h po
• Ammonia Ipecacuaha Mixture
• 10-20 ml three to four times daily po

61
Cough preparations (Contd)

• Mucolytics
• Reacts directly with mucus to make it more
  watery. This should help make the cough more
  productive

62
Cough preparations (Contd)

• Dosage
• Acetylcysteine
• 100 mg two to four times daily
• 200 mg two to three times daily
• 600 mg once daily
• Bromhexine
• 8-16 mg three times daily po
• Carbocisteine
• 750 mg three times daily, then 1.5 g daily in
  divided doses

63
Nasal Decongestants

• Sympathomimetics are used to reduce nasal
  congestion
• Stimulate alpha1-adrenergic receptors on nasal
  blood vessels, which causes vasoconstriction
  hence shrinkage of swollen membranes

64
Nasal Decongestants (Contd)

• Topical administration
• Response is rapid intense
• Oral administration
• Response are delayed, moderate prolonged

65
Nasal Decongestants (Contd)
Drug Formulation Dosage Dosage
Adult Child
Oxymetazoline Nasal Drops 0.025 20 ml - 2-3 drops q12h (2-5 yrs)
Oxymetazoline Nasal Spray 0.05 15 ml 2-3 sprays q12h Same as adults for children gt6 yrs
Phenylephrine Nasal Drops 0.5 10 ml Several drops q2-4h -
Xylometazoline Nasal Drops 0.05 / 0.1 2-3 drops q8-10h (0.1) 2-3 drops q8-10h (2-12 yrs) (0.05)
66
Nasal Decongestants (Contd)

• Adverse effects
• Rebound congestion develops with topical agents
  when used for more than a few days
• CNS stimulation (such as restlessness,
  irritability, anxiety and insomnia) occurs with
  oral sympathomimetics

67
Nasal Decongestants (Contd)

• Adverse effects (Contd)
• Sympathomimetics can cause vasoconstriction by
  stimulating a-1 adrenergic receptors. More common
  with oral agents
• Sympathomimetics cause CNS stimulation, and can
  produce effects similar to amphetamine. Hence,
  these drugs are subject to abuse

68
Nasal Decongestants (Contd)

• Nursing alerts
• Overuse of topical nasal decongestants can cause
  rebound congestion, meaning that the congestion
  can be worse with the use of drug. To minimise
  this, drug therapy should be discontinued
  gradually.
• The use of topical agents is limited to no more
  than 3 to 5 days

69
Nasal Decongestants (Contd)

• Nursing alerts (Contd)
• The patients blood pressure and pulse should be
  assessed before a decongestant is administered
• Inform the patient that nasal burning and
  stinging may occur with topical decongestants

70
Intranasal Corticosteroids

• Intranasal Corticosteroids
• Most effective for treatment of seasonal and
  perennial rhinitis
• Have inflammatory actions and can prevent or
  suppress all major symptoms of allergic rhinitis
  including congestion, rhinorrhea, sneezing, nasal
  itching and erythema

71
Intranasal Corticosteroids (Contd)
Drug Formulation Dosage Dosage
Adult Child
Beclomethasone Dipropionate Nasal Spray 50 mcg / dose 1 spray in each nostril four times daily Max. 10 sprays / day 4-6 sprays / day
Beclomethasone Dipropionate Nasal Spray 50 mcg dose (Aqueous) 2 applications into each nostril twice to four times daily Max. 400 mcg daily Same as adult (gt6 yrs) Not recommended in children lt6yrs
72
Intranasal Corticosteroids (Contd)
Drug (Contd) Formulation Dosage Dosage
Adult Child
Budesonide Nasal Spray 50 mcg / dose (Aqueous) 1-2 sprays into each nostril twice daily after 2-3days 1 spray into each nostril twice daily Not recommended for age 12 yrs or below
Budesonide Turbuhaler 100mcg / dose 400 mcg in the morning given as 2 applications into each nostril then reduce to the smallest amount necessary -
73
Intranasal Corticosteroids (Contd)
Drug (Contd) Formulation Dosage Dosage
Adult Child
Fluticasone Nasal Spray 50 mcg / dose (Aqueous) 2 sprays into each nostril in the morning Max 8 sprays/day 1 spray into each nostril in the morning (4-11yrs) Max 4 sprays/day
Mometasone Nasal Spray 50 mcg / dose 2 sprays in each nostril once daily 1spray in each nostril as maintenance Max 8 sprays/day 1 spray in each nostril once daily (3-11yrs)
74
Intranasal Corticosteroids (Contd)

• Adverse effects
• Mild
• Most common effects are drying of nasal mucosa
  sensations of burning or itching

75
Chronic Obstructive Pulmonary Disease (COPD)

• Umbrella term for various conditions
  characterized by limitation of airflow that is
  not fully reversible
• Chronic airflow limitation caused by a mixture of
  small airway disease and parenchymal destruction
• Airflow limitation is often progressive
• Associated with an abnormal inflammatory response
  of lungs to noxious substances
• PREVENTABLE and TREATABLE disease

76
Relationship between COPD and emphysema/chronic
bronchitis

• Emphysema
• Destruction of the gas exchanging surfaces of the
  lung (alveoli)
• Pathological term that describes only one of
  several structural abnormalities present in
  patients with COPD
• Chronic bronchitis
• Presence of cough and sputum production for at
  least 3 months in each of two consecutive years
• Remains a clinically and epidemiologically useful
  term, but does not reflect the major impact of
  airflow limitation on morbidity and mortality in
  COPD patients
• The emphasis on these conditions are not included
  in the definition of COPD in current relevant
  clinical guidelines

77
Mechanisms of COPD
78
Risk factors

• Genes
• Exposure to particles
• Tobacco smoke
• Occupational dusts, organic and inorganic
• Indoor air pollution from heating and cooking
  with biomass in poorly vented dwellings
• Outdoor air pollution
• Lung Growth and Development
• Oxidative stress
• Gender (appears to be related to cigarette use?)
• Respiratory infections
• Socioeconomic status
• Nutrition
• Comorbidities (e.g. asthma)

79
GOLD report COPD Staging System
Stage / Severity Postbronchodilator FEV1/ FVC and FEV1 pred. Characteristics
Stage I Mild FEV1/FVC lt 0.70 FEV1 80 predicted chronic cough and sputum production may be present, but not always
Stage II Moderate FEV1/FVC lt 0.70 50 FEV1 lt 80 predicted shortness of breath typically developing on exertion and cough and sputum production sometimes also present
Stage III Severe FEV1/FVC lt 0.70 30 FEV1 lt 50 predicted greater shortness of breath, reduced exercise capacity, fatigue, repeated exacerbations that almost always have an impact on patients quality of life
Stage IV Very severe FEV1/FVC lt 0.70 FEV1 lt 30 predicted or FEV1 lt 50 predicted plus chronic respiratory failure quality of life is very appreciably impaired and exacerbations may be life threatening
FEV1 forced expiratory volume in one second FVC forced vital capacity Respiratory failure arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level FEV1 forced expiratory volume in one second FVC forced vital capacity Respiratory failure arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level FEV1 forced expiratory volume in one second FVC forced vital capacity Respiratory failure arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level
80
Asthma and COPD

• Underlying cause is different
• Asthma eosinophilic inflammation
• COPD neutrophilic inflammation
• COPD can coexist with asthma
• While asthma can usually be distinguished from
  COPD, in some individuals with chronic
  respiratory symptoms and fixed airflow limitation
  it remains difficult to differentiate the two
  diseases

81
Differences in causes of COPD and asthma
82
Clinical features in COPD and asthma
83
Pharmacotherapy

• None of the current available medications can
  alter the natural course of COPD or modify the
  rate of decline in lung function
• Aims (as per GOLD report)
• Relieve symptoms
• Prevent disease progression
• Improve exercise tolerance
• Improve health status
• Prevent and treat complications
• Prevent and treat exacerbations
• Reduce mortality

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Bronchodilators

• Bronchodilator medications are central to symptom
  management in COPD
• Inhaled therapy is preferred
• The choice between beta agonist, anticholinergic,
  theophylline, or combination therapy depends on
  availability and individual response in terms of
  symptom relief and side effects

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Bronchodilators (Contd)

• Bronchodilators are prescribed on an as-needed or
  on a regular basis to prevent or reduce symptoms
• Long-acting inhaled bronchodilators are more
  effective and convenient
• Combining bronchodilators may improve efficacy
  and decrease the risk of side effects compared to
  increasing the dose of a single bronchodilator

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Corticosteroids

• Effects of oral and inhaled corticosteroids in
  COPD are much less dramatic than in asthma, and
  their role in the management of stable COPD is
  limited to specific indications

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Oral corticosteroids

• Use of a short course (two weeks) of oral
  corticosteroids to identify COPD patients who
  might benefit from long-term treatment with oral
  or inhaled corticosteroids is recommended
• Due to lack of evidence of benefit, and the issue
  of side effects, long-term treatment with oral
  corticosteroids is not recommended in COPD

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Inhaled corticosteroids

• Regular treatment is appropriate for symptomatic
  Stage III and Stage IV CPOD and repeated
  exacerbations (for example, 3 in the last 3
  years)
• Treatment has been shown to reduce the frequency
  of exacerbations and thus improve health status
• More effective when combined with a long-acting
  beta agonist

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