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
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
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.
17.
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
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.
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)
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.
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.
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
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.
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
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
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
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.
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
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