‫بسم هللا الرحمن الرحيم‬

Pharmacology of the Respiratory

System
 Respiratory System
 Functions of respiratory system:
 Breathing process (exchange of Oxygen and
Carbon Dioxide).
 Enable speech production.

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 Structures of Respiratory System

 Upper respiratory tract

➢nose, mouth, pharynx,
epiglottis, larynx and
trachea
 Lower respiratory tract
➢bronchial tree and
lungs

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 Drugs and the respiratory system
 Drugs that act on the respiratory system
include:
1. Antiasthmatic drugs.
2. Decongestants.
3. Expectorants.
4. Antitussives.
5. Mucolytics.
6. Drugs used in tuberculosis treatment.

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 Autonomic regulation of respiration
 β-Adrenoceptors are abundantly expressed on
human airway smooth muscle (as well as mast
cells, epithelium, glands and alveoli). β agonists
relax bronchial smooth muscle, inhibit mediator
release from mast cells, and increase mucociliary
clearance.
 Parasympathetic innervation of bronchial smooth
muscle occurs through muscarinic receptors it
mediates bronchoconstriction and mucus
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secretion.
 Bronchial Asthma
 It is a recurrent, reversible, obstruction of
airways in response to stimuli which are not in
themselves, noxious and don’t affect non
asthmatic person.
 Asthmatic patients experience intermittent
attacks of wheezing, shortness of breath
(dyspnea) with difficulty especially in breathing
out, and sometimes cough.

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 Allergic asthma
 (type I hypersensitivity reaction)
 Attacks occur in a sensitized individuals
where allergen interacts with IgE antibodies
→ histamine release and other mediator,
(30% of the asthmatic patients).
 Allergens bind to specific IgE antibodies
leading to deregulation and release of
mediators (histamine, PGD2, LTD4, and
LTC4)
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 Non allergic asthma
 Irritants (irritants chemicals, cold, drug,
allergen, pollutants, and infection) stimulate
irritant receptors (in respiratory epithelium)
→ release of mediators which activate mast
cells and other cells, (because of
inflammation charges in the airways) this
leads to hyperresponsiveness or
hyperreactivity leading to reversible airways
obstruction.
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 Asthma phases
A. The immediate phase (bronchoconstriction):
Occurs abruptly due to spasm of the bronchial
smooth muscles, cells involved are the mast
cells, but other cells can contribute, platelets
and macrophages.
B. The late phase (inflammatory reaction):
Occurs at variable times after exposure to the
stimuli may be nocturnal, it is an acute
inflammatory reaction.
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 'Aspirin-sensitive' asthma
 Non-steroidal anti-inflammatory drugs (NSAIDs),
especially aspirin, can precipitate asthma in
sensitive individuals.
 Such aspirin-sensitive asthma is relatively
uncommon (< 10% of asthmatic subjects).

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 Drugs used to treat asthma
 There are two categories of antiasthmatic drugs:
1. Bronchodilators.
2. Anti-inflammatory agents.
 Bronchodilators reverse the bronchospasm of
the immediate phase, while anti-inflammatory
agents inhibit or prevent the inflammatory
components of both phases.
 Some drugs classified as bronchodilators also
have some anti-inflammatory effect.

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 Bronchodilators
 The main drugs used as bronchodilators are:
1. β2-adrenoceptor agonists.
2. Methylxanthines.
3. Leukotrienes receptor antagonists.
4. Muscarinic receptor antagonists.

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 Bronchodilators
 Bronchodilatation is promoted by cAMP,
intracellular levels of cAMP can be increased by
β2 agonists (stimulate adenylate cyclase, AC) and
phosphodiesterase (PDE) inhibitors such as
theophylline (which slow the rate of adenylate
cyclase degradation).

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 Bronchodilators
 Bronchoconstriction can be inhibited by:
1. Muscarinic antagonists (e.g. ipratropium).
2. Adenosine receptor antagonists
(Methylxanthines: e.g. theophylline
(adenosine cause bronchoconstriction ).
3. Leukotrienes receptor antagonists: e.g.
montelukast.

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 Β2 adrenoceptors agonists
 They are drug of choice for immediate phase,
they dilate bronchioles by a direct effect on
the beta- adrenoceptors, and they inhibit
mediator release and may inhibit vocal tone.
 E.g. salbutamol, terbutaline (short-acting),
they given by inhalation, aerosol, nebulized
solution and orally also by injection in
emergency use for acute bronchospasm.
 Longer-acting agents: e.g. salmeterol and
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formoterol.
 Muscarinic receptor antagonists
 They competitive antagonist inhibit ACH
mediated constriction of bronchial airways; also
decrease vagal stimulated mucus secretion.
 The main compound used as a bronchodilator is
ipratropium. Tiotropium is also available; it is a
longer-acting drug used in maintenance treatment
of COPD.
 Combination of both an anticholinergic and a β2
agonist may be helpful in patients who have
inadequate response to a single inhaled
19 bronchodilator.
 Methylxanthines
 Naturally occurring includes theophylline,
theobromine and caffeine, synthetic include
aminophylline.
 Theophylline has been largely replaced with β2
agonists and corticosteroids due to its narrow
therapeutic window, adverse effect profile, and
potential for drug interactions.
 Theophylline overdose may cause seizures or
potentially fatal arrhythmias.

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 Leukotriene receptor antagonists
 All the leukotrienes (LTC4, LTD4 and LTE4) act on
the same high-affinity leukotriene receptor termed
LT1. Two receptors (LT1 and LT2 ).
 The 'lukast' drugs (montelukast and zafirlukast)
antagonize only LT1they reduce
bronchoconstriction and inflammatory cell
infiltration.

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 5- lipoxygenase inhibitors
 Zileuton is a 5- lipoxygenase inhibitor.
 It relieves bronchoconstriction from exercise.
 May cause liver toxicity.
 It inhibits microsomal P450s.

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 Corticosteroids (glucocorticoids)
(anti inflammatory)
 They given prophylactically they inhibit the late
phase they decrease inflammatory cell infiltration
into the airways and edema formation.
 They include beclomethasone, budesonide,
fluticasone (given by inhalation) and
prednisolone (oral).

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 Corticosteroids
 Inhaled corticosteroids (ICS) are the drugs of
choice for long-term control in patients with any
degree of persistent asthma.
 MOA: Corticosteroids inhibit the release of
arachidonic acid through phospholipase A2
inhibition, thereby producing direct anti-
inflammatory properties in the airways.
 After several months of regular use, ICS reduce
the hyperresponsiveness of the airway smooth
muscle to a variety of bronchoconstrictor stimuli, 24
such as allergens, irritants, cold air, and exercise.
Side Effects of Corticosteroids

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 Cromolyn sodium (cromoglycate) and
nedocromil sodium
 They are 'mast cell stabilizers’, that rpevent
histamine release from mast cells.
 Although very safe, they have only weak anti-
inflammatory effects and short duration of action.
 Given prophylactically, they reduce both the
immediate and late-phase asthmatic responses and
reduce bronchial hyper-reactivity.

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Guidelines for the treatment of asthma

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ICS = inhaled corticosteroid. LABA = long-acting beta2
agonist.
 Severe acute asthma (status
asthmaticus)
 Severe acute asthma is a medical emergency
requiring hospitalization. Treatment includes:
1. Oxygen (in high concentration).
2. Inhalation of salbutamol given by nebulizer,
3. Intravenous hydrocortisone followed by a
course of oral prednisolone.
4. Additional measures occasionally used include
nebulized ipratropium, intravenous
salbutamol or aminophylline, and antibiotics
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Rhinitis (stuffy nose)
 Rhinitis (stuffy nose)
 It is a decrease in nasal airways due to
thickening of the mucosa and increase mucus
secretion.
 The primary symptom of rhinitis is nasal
dripping (rhinorrhea, runny nose), nasal
itching, nasal congestion and sneezing.

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 Rhinitis (stuffy nose)
 It is caused by chronic or acute
inflammation of the mucous membrane of
the nose due to:
➢ Viruses.
➢ Bacteria .
➢ Irritants.

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 Rhinitis (stuffy nose)
 Treatment:
1. Topical and systemic decongestants.
2. Steroid nasal sprays are effective and safe and
may be effective without oral antihistamines.
3. Systemic corticosteroids such as Triamcinolone
or Prednisone are effective at reducing nasal
inflammation, but their use is limited by their
short duration of effect and the side effects of
prolonged steroid therapy.
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 Decongestants
 Classified as systemic or topical.
 Systemic decongestants stimulate
the sympathetic nervous system (α1
agonists) to reduce swelling of the
respiratory tract’s vascular network.
 They include; ephedrine,
phenylpropanolamine, and
pseudoephedrine

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 Decongestants
 Topical decongestants when applied directly
to swollen mucous membranes of the nose,
they provide immediate relief from nasal
congestion.
 These drugs include ephedrine, epinephrine,
phenylephrine, naphazoline, oxymetazoline,
tetrahydrozoline, and xylometazoline.

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 Decongestants
 Topical decongestants act directly on the
alpha receptors of the vascular smooth
muscle in the nose, causing the arterioles to
constrict, resulting in very little of the drug
being absorbed.
 Topical decongestants provide two major
advantages over systemic decongestants:
1. Minimal adverse reactions.
2. Rapid symptom relief.
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 Decongestants
 Pharmacotherapeutics:
 Used to relieve the symptoms of swollen nasal
membranes resulting from: hay fever (allergic
rhinitis).
 Systemic decongestants are frequently given with
antihistamines, antipyretics-analgesics,
antitussives, and expectorants.

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