This document discusses drugs used to treat respiratory diseases like asthma and COPD. It begins by outlining the objectives of understanding drugs for conditions like asthma, COPD, allergic rhinitis. It then covers topics like respiratory physiology and disorders like asthma and COPD. Asthma is defined as an inflammatory airway disease causing obstruction. COPD involves chronic inflammation and irreversible airflow limitation. The document outlines management of these conditions including education, monitoring, and medications. Key classes of medications discussed are bronchodilators like beta-agonists, anticholinergics, cromones, leukotriene modifiers, glucocorticoids, and monoclonal antibodies. Long-term control and acute relief therapies are presented for

1. Drugs used in
Respiratory system

2. Pulmonary diseases
 Asthma
 Chronic obstructive pulmonary disease
(COPD)
 Allergic rhinitis and common cold
 Bacterial infections (URTI, LRTI) and
tuberculosis
 Malignancies
 Pulmonary hypertension

3. Objectives of Studying
 After this class, students should
understand and be able to explain:
 Drugs used in respiratory systems including
asthma, COPD, allergic rhinitis and
common cold
 Mechanism of actions of drugs used in the
respiratory systems
 Major ADR and DI of drugs used in the
respiratory systems

4. Topics for self study
 Physiology of respiratory system
 Regulation of respiratory system
 Regulation of muscle, blood vessels and glands of
the airway

5.  Respiratory center in medulla
 Partial pressure of carbon dioxide in
arterial blood (PACO2) and oxygen (PAO2)
 Sensory receptor and afferent neurons
 Connecting controls between cortex and
autonomic neurons
 Autonomic regulation : Parasympathetic
and Sympathetic nervous systems
 Non-adrenergic non-cholinergic neurons

6. Obstructive respiratory disorders
 Obstruction of breathing pathway and increase
in flow resistance.
 Asthma
 Chronic obstructive pulmonary disease (COPD)

7. Definition and characteristics of ‘Asthma’
 A disease of the lung characterized by
bronchial hypersensitivity and inflammation
causing an obstruction of the airways mostly
during attack.
 The obstruction caused by mediators,
especially inflammatory mediators.
 : Spasm of the bronchial muscle.
 : Edematous swelling of the bronchial wall.
 : Increase secretion

8. Normal
airways
Asthmatic
airways

9. Clinical Signs and Symptoms
 Signs:
Dyspnea, airflow limitation,
hyperinfiltration
 Symptoms:
Breathlessness, wheezing, chest
tightness

10. Asthma :
 Extrinsic factors
 Allergic asthma : pollens, dust, animal hairs (cat, dog)
etc..
Type 1 immediate hypersensitivity
reaction:
Increase IgE formation.
Mast cell degranulation.
Migration of monocytes (eosinophiles,
neutrophiles)

12. The autonomic nervous system in asthma
Cholinergic
nerve
Adrenergic
nerve
Non-cholinergic
non-adrenergic
nerve

13. Asthma
 Non-allergic asthma
Infection, tobacco smoke, cold air,
drug (e.g ibuprofen, aspirin)
Activation of irritant receptors -->
vagal nerve --> ACh release
Smooth muscle cells :M3 receptor
bronchocontriction and mast cell
degranulation

14. Asthma
 Intrinsic or cryptogenic
No antigenic or chemical factors
No significant smoking history
present later in life
poorer response to bronchodilator
rapid decline in pulmonary function

15. Asthma & COPD
 Asthma associated with COPD
 Pathological mechanism can not
separate asthma and COPD.

16. COPD
 A disease state characterized by airflow
limitation that is not fully reversible.
 The airflow limitation is usually both
progressive and associated with an abnormal
inflammatory responses of the lung to
noxious particles or gases.

18. COPD
 Chronic inflammation through out the
airways, parenchyma and pulmonary
vasculature, including increase of
inflammatory cells (e.g macrophages, T-
lymphocytes, neutrophile) in various parts of
the lung.
 Symptoms: chronic cough, sputum
production, or dyspnea and/or history of
smoking or exposure to risk factor

19. Differential diagnostic of asthma and
COPD
 Asthma
 Onset early in life (often
childhood).
 Symptoms vary from day
to day.
 Symptoms at night/early
morning.
 Allergy, rhinitis also
present.
 Family history of asthma.
 Largely reversible air
flow limitation.
 COPD
 Onset in mid-life.
 Symptoms slowly
progressive.
 Long smoking history.
 Dyspnea during
exercise.
 Largely irreversible
airflow limitation.

20. Goals for successful management of asthma
:
 Achieve and maintain control of symptoms.
 Prevent asthma exacerbations.
 Maintain pulmonary function as close to normal
levels as possible.
 Avoid adverse effects from asthma
medications.
 Prevent development of irreversible airflow
limitation.
 Prevent asthma mortality

21. Goals of effective COPD managements
 Prevent disease progression.
 Relieve symptoms.
 Improve exercise tolerance.
 Improve health status.
 Prevent and treat complications.
 Prevent and treat exacerbations.
 Reduce mortality.

22. Managements:
 Educate patient.
 Assess and monitor with both symptom
reports and measurements of lung function
(FEV1 and PEF).
 Avoid exposure to risk factors.
 (Smoking cessation for COPD)
 Establish individual medication plans.
 Establish individual plans for managing
exacerbation.
 Provide regular follow up care

23. Inhaled Routing
 Particle size : 2-5 micron
 Delivery devices :
Pressurized metered dose inhaler
(pMDI) and space chamber (spacer)
Nebulizer
Dry powder inhaler (Turbuhaler)

25. MDI with spacer
Nebulizier
Turbuhaler

26. Medications for asthma, COPD
Blockage of the release of
mediators.
Bronchospasmolysis.
Improvement of expectoration.

27. Inhibition of mediator release
 Cromones
 Sodium cromoglycate and nedocromil sodium
 Mechanism of action: Not fully understood.
 a non-specific chloride channel blocker.
 cell-selective and mediator selective suppressive
effect on inflammatory cells (e.g neutrophile,
eosinophile, machrophage)
 mast cell membrane stabilization
 inhibit neuronal reflex in the lung

28. Cromones
 Prophylaxis and controller therapy in mild
and persistent asthma.
 Not for therapy of asthma attack.
 Route of administration: inhaled (locally
effect, poorly absorbed).
 Side effect: rare, occasionally
bronchospasm, cough, irritation of the
throat.
 No drug interaction.

29. Leukotriene modifiers
 Receptor antagonists
 Cysteinyl leukotriene 1 (CysLT1) receptor
antagonist:
Montelukast
Pranlukast
Zafirlukast
 5-lipoxygenase inhibitor (Leukotriene
synthesis inhibitor)
 Zileuton ……….(withdrawn)

30. Receptor antagonist and leukotriene
synthesis inhibitor
Arachidonic
acid
5-Lipoxygenase -
activating protein
(FLAP)
5-Lipoxygenase
Leukotriene A4
LTC4, LTD4, LTE4
LT 1 receptor
airway smooth
muscle cells
LT receptor
antagonist
5-Lipogenase
inhibitor
FLAP
inhibitor

31. Leukotriene modifiers
 Role in therapy: second line drug therapy
 Effects: reduce symptoms, improve lung
function, variable bronchodilator effect and
reduce exacerbations.
 Less effect than low does of inhaled
glucocorticoids
 Used as add-on therapy to reduce the dose of
steroid
 Route of administration: oral

32. Leukotriene modifiers
 Side effects: few
 Leukotriene modifiers are well tolerated
 Zileuton--> liver toxicity (monitoring of liver test)

33. Bronchospasmolytic drugs
 b-agonists (b –sympathomimetic drugs)
 Xanthine derivatives or
methylxanthines
 Anticholinergic drugs
(parasympatholytic drugs)

34. b-agonists
 b-agonists mediate through b receptors
 ( 3 subtypes b1, b2, b3 ).
 70% of b-receptors in airway epithelium and
alveoli are b2 receptors.
 b2 receptors found in airway and vascular
smooth muscle.

35. b2 receptor activation

36. b2 receptor activation
 Smooth muscle relaxation
 Inhibitor of mediator release
 Reduce vascular permeability
 Change in mucociliary clearance and
functions
 Anti-inflammatory effect in long term
use

37. b2 agonists (BA)
 PK : Good
 Long acting ( > 12 hours) : Formoterol,
Salmeterol
 Short acting (4-6 hours) : Salbutamol,
terbutaline, fenoterol, pirbuterol,
procaterol
 Route of administration: inhaled, oral

38. Long acting inhaled b2 agonist (LABA)
 Role of therapy: control of asthma when
inhaled glucocorticosteroids fail to achieve
control of asthma.
 combination of inhaled glucocorticosteroids
and long acting b2 agonist
 Side effect: fewer systemic adverse
effects (e.g cardiovascular stimulation,
skeletal muscle tremor, hypokalemia)

39. Long acting oral b2 agonist
 Control nocturnal symptom of asthma
 Use as and addition to inhaled glucocorticosteroid.
Short acting (rapid-acting) inhaled b2
agonists
 Acute exacerbation (treatment of choice)
 Pretreatment of exercise-induced asthma
 Not for long term treatment of asthma
 Increase use indicating worsen asthma and lung
function.

40. Examples of β-receptor agonists
Salbutamol Terbutaline

41. Xanthine derivatives and
Methylxanthines
 Theophylline, theobromine, caffeine
 Mechanism of action : complex, unclear
 A non-selective inhibitor of
phosphodiesterases in airway smooth
muscle and inflammatory cell
 Bronchodilator effect (high dose, > 10 mg/l)
 Anti-inflammatory effect (low dose, 5-10 mg/l)

42. Mechanism of Theophylline

43. Selective PDE-4 inhibitor
 New drug development for COPD
 Roflumilast, Cilomilast, Tofimilast
 ADR : severe nausea, vomiting

44. Theophylline
 Role of therapy: long term treatment of
asthma with sustained-released theophylline
 Controlling asthma symptom and improving lung
function
 Route of administration: oral, parenteral
(relief symptom)
 Low therapeutic range: drug monitoring for
steady-state serum concentration (10-15
mg/l)

45. Theophylline
 Side effect : High dose  theophylline
intoxication
 Gastrointestinal symptoms: nausea,
vomiting
 Central nervous system: restlessness,
insomnia, headache, seizure
 Cardiovascular effect: tachycardia,
arrhythmia,
 Respiratory center stimulation
 Death

46. Theophylline
 Drug interaction:
 Increase drug plasma level: cimetidine, macrolide
antibiotics, ciprofloxacin, enoxacin
 Decrease drug plasma level: enzyme inducer e.g.
barbiturate, carbamazepine
 Cautions: Patients with epilepsy,
hyperthyroidism, cardiac arrhythmia, liver
disease and pregnancy

47. Anticholinergic drugs
 M3 receptor at airway smooth muscle cells
 bronchoconstriction
 Acetylcholine receptors blockage:
 Bronchodilator (inhibit M3 receptor)
 No anti-inflammatory effect

48. Muscarinic subtypes in the lung
Pre-ganglionic
nerve
Parasympathetic
ganglion
Nicotinic receptor
M1 receptr
M2 receptor
M3 receptor
Airway smooth
muscle
Post-ganglionic
nerve

49. Anticholinergic drugs
 Route of administration: inhaled
 Ipratropium bromide
 Oxitropium bromide
 Tiotropim bromide
 Add up therapy with b2 agonist for
exacerbation
 Side effect: mouth dryness, bitter taste

50. Tiotropium bromide
Ipratropium bromide

51. Glucocorticosteroid
 The most effective anti-inflammatory
medication for asthma treatment
 Inhaled glucocorticorsteroid (long term
treatment)
 Mechanism of action: anti-inflammatory
actions, suppression of airway inflammation
in asthma

52. Glucocorticoid receptor activation
 Gene transcription
 Anti-inflammatory proteins and enzymes e.g
cytokines, cyclo-oxygenase
 Cell functions
 inhibitory effect on inflammatory and structural
cells such as macrophages, eosinophiles,
neutrophiles, including endothelial cells, smooth
muscle and mucus glands.

53. Cellular effects of corticosteroid

54. Glucocorticoid
 Route of administration: inhaled, oral
 Beclomethasone dipropionate, budesonide,
flunisolide, fluticasone, triamcinolone acetonide
 Inhaled glucocorticosteroids (IGC)
 The most effective treatment of asthma
Improving lung function
decreasing airway hyperesponsiveness
reducing symptoms
reducing frequency and severity of
exacerbation
improving quality of life

55. Glucocorticoid
 Side effects
 Local: oropharyngeal candidiasis, dysphonia,
coughing
 Prevention: Spacers, mouth washing
 Systemic: adrenal suppression, growth
suppression, osteoporosis, cataracts,
glaucoma, metabolic abnormalities (glucose,
insulin, triglycerides) psychiatric
disturbances

56. Glucocorticoid
 Caution: using of systemic glucocorticoids in
asthma patient with TB, parasitic
infections, osteoporosis, guaucoma,
diabetes, severe depression, or peptic
ulcer.
 Hepes virus infection in long term using of
systemic glucocorticoids.

57. Anti-IgE monoclonal antibody
 Omalizumab
 Antibody specific against IgE portion binding to
IgE receptor on mast cell
 Inhibit the binding of IgE to mast cell
 Reduce asthma severity and corticosteroid
requirement, decrease exacerbation
 Cost

58. Histamine receptor antagonist
 Second-generation antihistamine
 e.g Ketotifen, acrivastin, loratadine,
astemizole, cetirizine, azelastine,
fexofenadine
 Mechanism of action: H1 receptor blockage-
-> inhibit allergic reactions
 Ketotifen: stabilization of mast cell membrane and
other inflammatory cells
 Loratadine: inhibition of leukotriene release

59. Histamine receptor antagonist
 Role in therapy : as add-on therapy
 Side effect: sedation, cardiac toxicity
(terfenadine and astimizole), weight gain
(ketotifen)
 Route of administration: oral

60. Recommended Medications for Asthma
by level of severity
Level of severity Daily medication Other treatment
Step 1
Intermittent asthma
None necessary
(short-acting b2 agonist
prn.)
Step 2
Mild persistent
IGC Sustained release
theophylline or
Cromone, or
Leukotriene modifier
Step 3
Moderate persistent
IGC + long-acting
inhaled b2agonist
IGC +sustained release
theophylline
IGC + long-acting oral
b2agonist
IGC + leuckotriene
modifiers
Step 4
Severe persistent
IGC + long-acting
inhaled β2agonist +
one or more of
theophylline,
leukotriene
modifier, oral GC

61. Recommended therapy for COPD
Short-acting
b2 agonist
prn
Anticholinergic
drugs
+
Short-acting
b2 agonist prn
Theophylline
+
Anticholinergic
drugs
+
Short-acting
b2 agonist prn
Steroid
+
Anticholinergic
drugs
+
Short-acting
b2 agonist prn
Intermittent
Mild persistent
Moderate
persistent
Severe persistent

62. Allergic rhinitis and common cold
 Immediate hypersensitiviy (allergic response,
type 1)
 Allergen (dust, pollen, animal hairs)
 Cold
 Virus, Coronavirus and Rhinovirus
 Symptoms: runny nose, flushing, tears, sneeze,
cough, congestion, headache as well as fever.

63.  Antihistamines
 Nasal decongestants
 Antitussives
 Expectorants and mucolytics

64. H1 receptor antagonists
 First generation:
 Rapid and mostly complete absorption by GI
 Stable lipid soluble: widely distributed throughout
the body and enter CNS.--> sedative
 Peak of action: 1-2 hours
 Duration of action: 4-6hours.
 Primarily metabolized by microsomal system in
liver (cytochrom 3A4)
 Ethanolamine, ethylaminediamine, piperazine
derivatives, alkylamine, phenothiazine derivatives,
cyprohepatine

65. H1 receptor antagonists
 Second Generation:
 Rapid and mostly complete absorption by GI.
 Less lipid soluble, less distribution to CNS.
 Peak of action: 1-2 hours.
 Duration of action: 12-24 hours (long duration).
 Primarily metabolized by microsomal system.
 Piperidine derivatives: Fexofenadine, Loratadine,
Cetrizine
 Terfenadine, Asthemizole: withdrawn
 (severe drug interactions with Erythromycin,
Ketoconazole (CYP 3A4 enzyme inhibitor)

66. Side effects and DI
 Sedation
 Dry mouth and throat, cough
 Less appetite : astemizole
 Weight gain : ketotifen, cyproheptadine
 Excitation and convulsion in children **
 Arrhythmia
 Postural hypotension
 Drug interaction: Cardiac toxicity (lethal
ventricular arrhythmia**severe)
 Tefenadine and astimezole vs ketoconazole,
itraconzole, erythromycin

67. Antihistamines
 First generation
 Dramamine (Dimenhydrinate) 50 mg, oral tid pc
 Benedryl (Diphyenhydramine) 25-50 mg,
 CPM (Chlopheniramine) 4-8 mg
 Dimetane (Bromphenilamine) 4-8 mg
 Atarax (Hydroxyzine) 25-100mg
 Merizine (Cyclizine) 25-50 mg
 Periactin (Cyproheptadine) 4 mg
 increase appetite

68.  Second generation
 Allergra (Fexofenadine) 60 mg, Oral, bid
 Claritin (Loratadine) 10 mg
 Zyrtec (Cetrizine) 5-10 mg

69. Decongestants
 a-Sympathomimetics or a-adrenergic
agonist
 Phenylethylamine derivertives :
ephedrine, psuedoephedrine,
phenylephrine, phenylpropanolaime,
propylhexedrine, methoxamine
 Imidazoline derivertives : naphazoline,
tetrahydrozoline, oxymetazoline,
xylometazoline (more potent and longer
duration than phenylethylamines)

70. a-adrenergic agonist actions
 a-receptor on vascular smooth muscle cells
 Vasocontriction (both artery and vein) -->
decrease blood flow to nasal mucosa -->
decrease swelling
 other smooth muscle cells : contraction
 Eye : contraction (mydriasis)
 Uterus : contraction
 Metabolism : increase glucose plasma
concentration

71.  Topical route : nasal drops, sprays, inhalers
 Local effect, fast onset, short duration
 Phenylephrine, propylhexadrine, naphazoline,
xylometazoline.
 Oral route: capsule, syrup
 Systemic effect, slow onset, long duration
 phenylpropanolamine, pheylephrine and
pseudoephedrine

72. Side effects
 Topical : rebound congestion (longer than 5
days), dryness, sneezing, chronic rhinitis
(long term use)
 Children patient: overdose naphazolone and
tetrahydrozoline  CNS repression or coma
 Systemic : insomnia, excitation,
arrhythmia, hypertension, tachycardia,
nausea, vomiting, bladder sphincter
stimulation, sweating
 Overdose CNS repression and coma

73. Precaution and contraindication
 Patient with diabetes, hyperthyroidism,
hypertension, angina pectoris, prostatic
hypertrophy, glaucoma, using tricyclic
antidepressant
 Children and elderly patient
 Drug interaction
 MAOI, theophylline, tricycle
antidepressant

74. Examples of sympathomimetic drugs
Ephedrine Pseudoephedrine/Triprolidine
ยาควบคุมพิเศษ
Xylometazoline

75. Antitussives
 Cough : cough center (brain stem) and
cough receptor (bronchial spaces)
 Antitussives or cough suppressants usually
inhibit cough reflex for “dry cough” with
no dangerous of mucus accumulation.

76. Antitussives
 Opioid antitussive: codeine, hydrocodone,
hydromorphone
 Non-opioid antitussive: dextromethorphan,
noscapine, levopropoxyphene, napsylate and
benzonatate

77. Coughing reflex

78. Opioid antitussive
 Suppress cough center in the brain
(medulla)
 Dry cough
 Codeine (good cough suppressant)
 Analgesic at high dose
 Suppress respiratory center
 Good GI absorption, onset 15-30 min, duration 4-
6 hours, metabolism in liver
 Side effect : nausea, vomiting, constipation,
addiction in long term use
 Caution use in patient with asthma and COPD,
using psychotic drugs, alcohol, MAOI

79. Nonopioid antitussives
 Dextromethophan (d-isomer of codeine)
 Dry cough
 Suppress cough center via increase threshold (as
good as codeine)
 No analgesic and addictive effects. No
respiratory suppression
 Good GI absorption, onset 15-30 min, duration 5-
6 hours
 Side effect: few such as nausea, vomiting,
dizziness
 Caution: patient with asthma, COPD, smoking,
using CNS suppressant.

80.  Noscapine : derivative of alkaloid from opium,
as good as codeine in cough suppression
 Levopropoxyphene napsylate: less potent than
codeine
 Benzonatate : polyglycol derivative, as good
as codeine in cough suppression
 Act on stretch receptors and cough receptor in the
lung, blocking afferent pathway of cough reflex
 Local anesthetics
 onset 15-20 min, duration 3-8 hours
 Side effect: few, such as headache, dizziness,
constipation, CNS stimulation at high dose

81. Expectorants
 A compound facilitate and accelerate the
removal of bronchial secretions from the
bronchi and trachea
 increase bronchial secretion and liquify
the mucus and direct effect on mucus-
producing cells
 enhance the movement of secretion and
removal by coughing

82. Guaifenesin (Glyceryl guaiacolate)
 Stimulate gastric receptor in stomach
 gastropulmonary mucokinetic vagal reflex
 increase liquidfied secretion
 cough
(to clear thick mucus)
 decrease cough

83. Guaifenesin (Glyceryl guaiacolate)
 Side effect: nausea, vomiting, GI
disturbances
 Cautions: patient with chronic cough
(asthma, COPD), smoking

84. Potassium Iodide (KI)
 Increase gastricpulmonary mucokinetic
vagal reflex --> increase liquidfied
secretions and decrease viscosity
 Iodide toxicity : bleeding in GI tract,
arrhythmia, hypothyroidism, goiter,
Iodism
 Caution: patient with hyperthyroidism,
lung disease, cardiac and renal disorder,
pregnancy
 Drug interaction : potassium-sparing
diuretic, anti-thyroid agents

85. Mucolytics
 Change physicochemical properties of
secretions, decrease viscosity
 Change properties of mucus composing of
mucopolysaccharide (mucoprotein). The
drug breaks disulfide bond between
glycoprotein resulting in clearer mucus.
 Bromhexine and ambroxol
 Acetylcysteine (reducing agent)
 Carbocisteine

86.  Bromhexine
 Degradation of acidic mucopolysaccharide and
stimulate serous glandular cells.
 Increase secretions and decrease sputum
viscosity.
 Ambroxal (use in chronic chronchitis)
 Main metabolite of bromhexine
 Surfactant effect (additive effect): decrease
surface tension of secretion, protection alveoli
collapsing at the end of expiration
 Side effects: few, nausea, vomiting, diarrhea, dry
mouth, dizziness

87.  Acetylcysteine or N-acetylcysteine
 Amino acid L-cysteine derivative
 Reduce disulfide bond between
mucopolysaccharide
 Increase action at high pH (pH 7-9)
 Side effects: bronchospasm (asthma), GI
disturbances, rash

88.  Carbocisteine
 mucoregulatory action
 Interfere with the synthesis of mucus and
enhance formation of mucus with low viscosity
 Decrease bronchial mucosa inflammation
 Not a reducing agent, no disulfide bond break
 Side effects: few, nausea, diarrhea, stomach
ache, GI bleeding
 Caution: peptic ulcer patient

89. References:
 Global Strategy for Asthma Management and
Prevention Issued January 1995 (revised 2010),
www.ginasthma.org
 Global Strategy for The Diagnosis, Management,
and Prevention of Chronic Obstructive Pulmonary
Disease, NHLBI/WHO Workshop report,
www.goldcopd.org
 Laurence LB, Lazo JS, Parker KL. Goodman &
Gliman’s The pharmacological Basis of Therapeutics
11th edition, 2006
 Katzung BG. Basic & Clinical Pharmacology 11th
edition,2009