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RESPIRATORY SYSTEM
Department of Pharmacology
Medical Faculty Brawijaya University
RESPIRATORY SYSTEM
Adrenergics Steroids
Nervousness Local mucosal dryness
Insomnia and irritation
Palpitations
Tremors
(systemic effects due to
adrenergic stimulation of the
heart, blood vessels, and CNS)
Antitussives
Cough Physiology
• Coughing is a complex reflex that depends on
functions in the CNS, the PNS, and the
respiratory muscles.
• It is a defense mechanism that aids the removal
of foreign particles like smoke and dust.
• Respiratory secretions and foreign objects are
naturally removed by the
• Cough reflex
• Induces coughing and expectoration
• Initiated by irritation of sensory receptors in the
respiratory tract
Coughing
Most of the time, coughing is beneficial
• Removes excessive secretions
• Removes potentially harmful foreign substances
In some situations, coughing can be harmful,
such as after hernia repair surgery
• In general, treating a productive cough is not
appropriate, as it is performing a useful
function.
• An unproductive cough, usually results from an
irritated oropharynx and can be troublesome.
Two basic type of cough
Productive cough
o Congested, removes excessive secretions
Nonproductive cough
o Dry cough (caused by irritation)
Antitussives
Drugs used to stop or reduce coughing
• Opioid and nonopioid (narcotic and non narcotic)
• Used only for nonproductive coughs!
Opioids
• Suppress the cough reflex by direct action on the cough
centre in the medulla (CNS)
Examples:
• Codeine
• Hydrocodone
Non opioids
• Suppress the cough reflex by numbing the stretch
receptors in the respiratory tract and preventing the
cough reflex from being stimulated
Examples:
• Dextromethorphan (DMP), Noskapin
Antitussives: Indications
Used to stop the cough reflex when the cough is
nonproductive and/or harmful
EXPECTORANTS:
CONTRAINDICATIONS ?
Mucolytic
Ede ma
Eo sino phils
Bro nc ho -
PMN c o ns tric tio n
Smo o th muscle
Late Response
Muc us hy pe rs e c re tio n
Cilia ry
func tio n
Epithe lia l
da ma ge
Effe re nt (va ga l)
ne rve dis c ha rge
Affe re nt ne rve
dis c ha rge
Bro nc ho -
c o ns tric tio n
Ag (polutan, alergen)
MEDIATOR
Symptom Hyperreactivity
THERAPY
Ag (polutan, alergen)
avoid
Ag-Ab/IgE di mast cell
cromolin, steroid
MEDIATOR
agonist, steroid
theophyllin,
anti cholinergic
Early response : Late response :
Bronchoconstriction Inflamation
Symptom Hyperreactivity
Pharmacotherapy of Bronchial Asthma :
1. Bronchodilator
2. Anti inflamatory drug
3. (Prophilactic drugs)
Bronchodilators
Bronchodilators
• Adrenergic agonists
• Methylxanthines
• Anticholinergics
Adverse effects
tremor, hypokalemia, tachycardia
Preparation
• Albuterol (generic, Proventil, Ventolin)
Inhalant: 90 mcg/puff aerosol; 0.021, 0.042, 0.083, 0.5,
0.63% solution for nebulization
Oral: 2, 4 mg tablets; 2 mg/5 mL syrup
Oral sustained-release: 4, 8 mg tablets
• Metaproterenol (Alupent, generic)
Inhalant: 0.65 mg/puff aerosol in 7, 14 g containers; 0.4,
0.6, 5% for nebulization
• Terbutaline (generic, Brethine)
Oral: 2.5, 5 mg tablets
Parenteral: 1 mg/mL for injection
• Formoterol (Foradil)
Inhalant: 12 mcg/unit inhalant powder; 1% solution for
nebulization
• Salmeterol (Serevent)
Inhalant powder: 50 mcg/unit
B. Methylxanthines
Mechanism of Action
a. Phosphodiesterase inhibitor, therefore,
increased cAMP relaxation
b. blocks the action of adenosine
Indication
Dilation of airways in asthma, chronic bronchitis,
and emphysema
Mild to moderate cases of acute asthma
Adjunct agent in the management of COPD
Theophylline affects multiple cell types in the
airway.
B. Methylxanthines
Kinetics
Administration: usually given orally; IV
– short biological half-life;
‘slow-release’ preparations
Side effects:
narrow therapeutic window
generally safe; nausea, cardiac
arrhythmias and convulsions.
B. Methylxanthines
Drug interactions
the serum theophylline concentration can be
decreased by (enzyme inducer)
barbiturates
benzodiazepines
cigarete smoke
increased by
cimetidine
erythromycin; M. peumoniae
ciprofloxacin; Gram -
allopurinol
Drugs
• Theophylline (generic, Elixophyllin, Slo-Phyllin,
Uniphyl, Theo-Dur, Theo-24, others)
Oral: 50 mg/5 mL elixirs
Oral extended-release, 12 hours: 100, 200, 300, 450 mg
tablets
Oral extended-release, 24 hours: 100, 200, 300 mg
tablets and capsules;
400, 600 mg tablets
Parenteral: 0.08, 1.6, 2.0, 3.2, 4 mg/mL, theophylline
and 5% dextrose for injection
• Aminophylline (theophylline ethylenediamine, 79%
theophylline) (generic)
Oral: 100, 200 mg tablets
Parenteral: 250 mg/10 mL for injection
C. Anticholinergics
• Anticholinergic
drugs inhibit
vagally
mediated airway
tone
C. Anticholinergics;
muscarinic receptor antagonists
1. Atropine sulfate – not used today in treatment of asthma
because of too many side effects (urinary retention,
tachycardia, loss of visual accommodation, and agitation)
2. New Agents: ipratropium bromide, oxitropium bromide
poorly absorbed from the lung and do not cross blood-brain
barrier; less systemic adverse effects.
DRUGs
• Ipratropium (generic, Atrovent)
Aerosol: 17 (freon-free), 18 mcg/puff in 200 metered-
dose inhaler; 0.02% (500 mcg/vial) for nebulization
Nasal spray: 21, 42 mcg/spray
• Tiotropium (Spiriva)
Aerosol: 18 mcg/puff in 6 packs
Inhalation of drugs
ANTI-INFLAMATORY DRUGS
Anti-inflammatory and
prophylactic drugs
• Glucocorticosteroids
• Cromolyn sodium and nedocromil
sodium
1. Inhaled glucocorticosteroids:
triamcinolon, beclomethasone, budesonide
and fluticasone
2. Oral glucocorticosteroids for severe asthma:
prednisone, or prednisolone
3. Metabolized in liver by hydroxylation
4. Side effects
- suppression of the hypothalamus-pituitary
axis
- shunting of growth in children
Glucocorticoids
Mechanism of action
- inhibit inflammatory cell
infiltration into the airways
- reduce edema formation by acting
on the vascular endothelium
Mechanism of anti-inflammatory action of
corticosteroids in asthma
Effect of corticosteroids on inflammatory
and structural cells in the airways
Glucocorticoid : Clinical use
• Treatment of adrenal insufficiency
• Decrease inflammation
• Asthma & COPD
• Allergic reactions & rashes
• Other inflammatory processes
• Suppression of immune response
• Autoimmune processes
• Prevent transplant rejection
Mechanism of action;
not clearly understood
1. Prevents mast cell degranulation; ‘mast
cell stabilizer’; prevent the release of
inflammatory mediators including
histamine.
2. Also probably suppress the response of
exposed irritant nerves; effective for the
treatment of ‘asthmatic cough’.
Leukotriene pathway inhibitors
Antileukotrienes
X
Effects of
cysteinyl-
leukotrienes on
the airways and
their inhibition
by anti-
leukotrienes
Antileukotrienes: Drug Effects
By blocking leukotrienes:
• Prevent smooth muscle contraction of the
bronchial airways
• Decrease mucus secretion
• Prevent vascular permeability
• Decrease neutrophil and leukocyte infiltration
to the lungs, preventing inflammation
Antileukotrienes: Indications
• Prophylaxis and chronic treatment of
asthma in adults and children older
than age 12
• NOT meant for management of acute
asthmatic attacks
• Montelukast is approved for use in
children ages 6 and older
Antileukotrienes: Side
Effects
zafirlukast montelukast has fewer
• Headache side effects
• Nausea
• Diarrhea
• Liver dysfunction
Pharmacotherapy Asthma Bronchiale