Dr. Mahmoud Taleb University of Al - Azhar Gaza Palestine lama Khaled Al Banna

1. Chapter II: Drugs affecting onChapter II: Drugs affecting on
respiratory systemrespiratory system
Dr. Mahmoud H. Taleb
Assistant Professor of Pharmacology and Toxicology
Department of Pharmacology and Medical sciences
Faculty of Pharmacy- Al azhar University
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4. • Asthma:
• Bronchial asthma is a condition characterized by repeated
attacks of paroxysmal dyspnea. It is now recognizes that
chronic asthma involves a characteristic inflammatory
response in the airways that is present in patients with very
mild asthma. Bronchial hyperresponsiveness or an
exaggerated bronchoconstrictor response to many different
stimuli is characteristic of asthma. There is remains
considerable debate about the types of inflammatory cells
and mediators involved in asthma.
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5. • Lymphokines may be important mediators in
increasing the inflammatory response, and
interleukin-5 release by lymphocytes also may be
important in acting to prime the eosinophils in the
mucusa.
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Mechanisms of response to inhaled irritants

7. Drugs Used in Asthma: Introduction
• The clinical hallmarks of asthma are recurrent,
episodic bouts of coughing, shortness of breath,
chest tightness, and wheezing. In mild asthma,
symptoms occur only occasionally, eg, on exposure
to allergens or certain pollutants, on exercise, or
after a viral upper respiratory infection. More severe
forms of asthma are associated with frequent attacks
of wheezing dyspnea, especially atnight, and even
chronic limitation of activity. Asthma is the most
common chronic disabling disease of childhood, but
it affects all age groups
Dr. Mahmoud H. Taleb

8. Asthma therapies are thus sometimes
divided into two categories: "short-term
relievers" and "long-term controllers."
Short-term relief is most effectively achieved with bronchodilators, agents
that increase airway caliber by relaxing airway smooth muscle, and of
these the -adrenoceptor stimulants , a methylxanthine drug, and
antimuscarinic agents are also used for reversal of airway constriction.
Long-term control is most often achieved with an anti-inflammatory agen
such as an inhaled corticosteroid, with a leukotriene antagonist, or with
an inhibitor of mast cell degranulation, eg, cromolyn or Ketotifen.
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9. A. Goals of therapyA. Goals of therapy
• A. Reducing impairment:
• B. Prevent chronic and a. troublesome symptoms.
• C. Require infrequent use of inhaled short-acting B2
agonist for quick relief of symptoms.
• D. Maintain normal pulmonary function.
• E. Maintain normal activity levels (including exercise
and other physical activity and attendance at work or
• school).
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10. Drugs Used to Treat AsthmaDrugs Used to Treat Asthma
1-1-Bronchodilator drugs:Bronchodilator drugs:
Activation of β2-adrenoceptors on the smooth muscle of the airways causesActivation of β2-adrenoceptors on the smooth muscle of the airways causes
activation of adenylyl cyclase with a subsequent increase in the intracellularactivation of adenylyl cyclase with a subsequent increase in the intracellular
concentration of cyclic AMP.concentration of cyclic AMP.
• (A) Adrenergic agonists
• Inhaled adrenergic agonists with B-2 activity are the drugs of
choice for mild asthma that is, in patients showing
• only occasional, intermittent symptoms .Direct-acting B-
agonists are potent bronchodilators that
• relax airway smooth muscle.
• Quick relief: Most clinically useful B2 agonists have a rapid
onset of action (5-30 minutes) and provide relief for 4 to 6
hours.
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11. • They are used for symptomatic treatment of
bronchospasm, providing quick relief of acute
bronchoconstriction. [Note: Epinephrine is the drug
of choice for treatment of acute anaphylaxis.] β2
Agonists
• have no anti-inflammatory effects, and they should
never be used as the sole therapeutic agents for
patients with persistent asthma.
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12. • Monotherapy with short-acting β2 agonists may be
appropriate only for patients
• identified as having mild intermittent asthma, such
as exercise-induced asthma. The direct-acting β2-
selective
• agonists, such as terbutaline ,and albuterol offer the
advantage of providing maximally attainable
bronchodilation with little of the undesired
• effect of B1 stimulation.
• Adverse effects
• , such as tachycardia, hyperglycemia, hypokalemia,
and hypomagnesemia are minimized with dosing via
• inhalation versus systemic routes.Dr. Mahmoud H. Taleb 12

13. • B-Anticholinergic drugs:
• Atropine is a competitive blocker of acetylcholine at
muscarinic cholinergic receptors and thus can cause a
variety of effects due to loss of parasympathetic
activity, including blurring of vision, increase in heart
rate, and drying of secretions in the salivary glands
and respiratory tract. This limits its usefulness as a
bronchodilator. Atropine is best used by inhalation,
which reduces, but does not eliminate entirely, these
unwanted side effects.
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14. • Ipratropium bromide (Atrovent) is a quaternary
isopropyl-substituted derivative of atropine that can
not cross the blood-brain barrier and therefore has
practically no central effect; it also shows some
degree of bronchoselectivity. The actions of
ipratropium bromide are otherwise similar to those of
atropine, and its therapeutic use is confined to aerosol
administration. The drug is administered by inhaler
and each puff contains 20μg, the exact place of
ipratropium bromide in the treatment of asthma
remains somewhat uncertain, and the drug appears to
have little advantage over the selective β2-agonists.
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15. C- Methylxanthine
Theophylline, caffeine
several mechanism have been proposed
Mechanism of action of methylxanthine
1-It inhibits phosphodiesterase enz. → ↑ cAMP and cGMP
2- Adenosine (A1, A2 and A3) receptors antagonist almost
equally, which explains many of its cardiac effects
A2 receptors antagonist responsible for CNS stimulation &
smooth muscles relaxation
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18. • 2- Anti-inflammatory steroids:
• Glucocorticoid drugs such as prednisone,
prednisolone, dexamethasone and Budesonide are
known empirically to relieve airway obstruction in
bronchial asthma, but the mechanism of their action is
complex.
• The possible actions include:
• Anti-inflammatory activity.
• Reduction of tissue sensitivity to antigens.
• Inhibition of contraction of bronchial smooth muscle.
• Mucolytic action.
• Increased responsiveness of β2-adrenoceptors.
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Recently, glucocorticoid drugs such as beclomethasone
dipropionate and beclomethasone valerate, budnoiside,
predisone have been developed for administration by
inhalation. Inhalation of these compounds is as effective as oral
prednisone in patients starting on ste­roids. Only a small
amount of the steroid administered in this manner is
systemically absorbed. Therefore there is little or no systemic
effect or adre­nal suppression and the problem of growth
suppres­sion in children may be avoided. The major problem
with this form of therapy to date has been the development of
fungal infections (candidiasis) in the oropharynx in about 10%
of patients because of suppression of phagocytic activity by the
high local concentrations of corticosteroid.

20. • 3- Mast cell stabilizers
• Cromolyn sodium (sodium cromoglycate), and Ketotifen
• It inhibits the release of mediators such as histamine and
leukotrienes from the secretory granules of mast cells
following the challenge of antigen interacting with
specific IgE antibodies.. Therefore it is suggested that
cromolyn sodium acts as a nonspecific stabilizer of the
mast cell membrane and/or granules.
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21. • Cromolyn sodium is absorbed poorly from the
gastrointestinal tract and therefore is effective only
when deposited directly into the airways. Two
methods of administration are currently used for
asthma. In adults, the drug can be given by a
"Spinhaler" apparatus that causes a capsule to be
punctured so that its powdered contents are entrained
into inspired air and deposited in the airways. The
usual dose is 20 mg inhaled four times daily. In
children, who may have difficulty in using this
device, the drug may be given by aerosol.
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22. 4- Leukotriene Pathway Inhibitors
Efficacy in blocking airway responses to exercise and to
antigen challenge has been shown for drugs in both
categories: zileuton, a 5­lipoxygenase inhibitor, and
zafirlukast and montelukast, LTD4­receptor
antagonists. All have been shown to be effective
when taken regularly in outpatient clinical trials.
Their effects
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24. • 5- Monoclonal antibodies eg. Omalizumab
• Omalizumab is a recombinant DNA derived
monoclonal antibody that selectively binds to
• human immunoglobulin E (IgE). This leads to
decreased binding of IgE to the high-affinity IgE
receptor on the surface of mast cells and basophils.
Reduction in surface-bound IgE limits the degree of
release of mediators of the allergic response.
Omalizumab may be particularly useful for treatment
of moderate to severe allergic asthma in patients who
are poorly controlled with conventional therapy. Due
to the high cost of the drug (approximately $600 for a
150-mg vial), limitations on dosage, and available
clinical trial data, it is not presently used as first-lineDr. Mahmoud H. Taleb 24

25. • DRUGS AFFECTING THE COUGH
REFLEX
• The cough reflex is mediated by receptors located in
the mucosa or deeper structures of the larynx, trachea,
and major bronchi, and by mechanoreceptors that
detect changes in bronchial intramural tension.
Stimuli are transmitted via the vagus to the cough
center in the medulla. Efferent impulses originating
from the cough center are transmitted through cho­
linergic pathways to the abdominal and intercostal
muscles and to the diaphragm, producing sudden
explosive expiratory movements.
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26. • Antitussive Drugs:
• Opioid antitussive agents:
• Opioid analgesics are most effective in depressing the
cough center. Codeine thus appears to be a more
effective cough suppressant relative to its analgesic
activity. The usual antitussive dose is 15­20 mg as
required.
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27. • Codeine also has significantly less respira­tory
depressant effect than morphine. The development of
tolerance and physical dependence is a major
drawback to morphine­like drugs, and for this rea­
son, their long­term use as antitussive agents is dis­
couraged. They can, however, be used for short­term
cough suppression. Because of the low dose of
codeine required, and its relatively low addiction
liability, it may be more suitable than other opioid
drugs for long­term antitussive use
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28. Nonopioid antitussive agents:Nonopioid antitussive agents:
• Dextromethorphan is a synthetic opioid derivative that is
an effective antitussive agent, suppressing the response of
the cough center but lacking analgesic or habituating
properties. It is the d-isomer of levomethorphan, which is a
potent opioid analgesic.
• Other nonopioid drugs that have some antitussive activity
in addition to their other pharmacological actions include
phenothiazines, antihistamines, and benzononatate
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29. • Mucolytic Agents:
• Mucolytic inhalants are mucokinetic substances that
liquefy mucus and aid the elimination of excess solidified
mucus in patients with respiratory disease. Excess mucus
may be liquefied by proteolytic agents and disulfide bond
cleaving agents. Acetylcysteine. It possesses a reactive
sulfhydryl group that splits the disulfide bonds of the
mucin molecule and thereby reduces the viscosity of
mucus. This drug is an extremely effective mucokinetic
agent, but it is little used because it causes many side
effects such as stomatitis, nausea, vomiting, rhinorrhea,
and especially bronchospasm. Bromohexine (Rx
Bisolvon, Solvex ,, Mucocare) It stimulates lysosomal
activity , leads to hydrolysis of mucopolysaccharides and
decrease the viscosity of the mucus
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30. Drugs Used to Treat Allergic Rhinitis
• Rhinitis is an inflammation of the mucous
membranes of the nose and is characterized by
sneezing, itchy nose/eyes, watery rhinorrhea, and
nasal congestion. An attack may be precipitated by
inhalation of an allergen (such as dust, pollen, or
animal dander). The foreign material interacts with
mast cells coated with IgE generated in response to a
previous allergen exposure ,The mast cells release
mediators, such as histamine, leukotrienes, and
chemotactic factors, that promote bronchiolar spasm
and mucosal thickening from edema and cellular
infiltration.
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31. • Combinations of oral antihistamines with
decongestants are the first-line therapies for allergic
rhinitis. Systemic effects associated with these oral
preparations (sedation, insomnia, and, rarely, cardiac
arrhythmias) have prompted interest in topical
intranasal delivery of drugs.
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32. Drugs used to treat allergic rhinitisDrugs used to treat allergic rhinitis
• A. Antihistamines (H1-receptor blockers) eg.
Chlorophenermine malate,cyproheptadine,
loratidine, cetrizine, and fexofenadine
• B. α-Adrenergic agonists eg, phenylephrine.
Ephedrine , oxymetazoline and naphazoline.
• C. Corticosteroids eg. fluticazone, Budesonide
• D. Cromolyn and ketotifen
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33. Thank you!Thank you!
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