Download - Pharmacology of the Respiratory Tract
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What is bronchial asthma?
It is chronic inflammatory disorder of airways
In susceptible individuals, this
inflammation causes recurrent episodes of:
1.Wheezing
2.Breathlessness
3.Chest tightness
4.Cough
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These episodes are associated with wide
spread airflow obstruction that is often
reversible
Airflow obstruction in asthma is due to
bronchoconstriction resulting from:
1.contraction of bronchial smooth muscle
2.Inflammation of the bronchial wall
3. mucus secretion
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The inflammatory changes in the airways
associated with bronchial hyper-
responsiveness (abnormal sensitivity to
stimuli).
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Comparison of bronchi of normal & asthmatic
individuals
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Comparison of bronchi of normal & asthmaticindividuals
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Stimuli that cause asthmatic attack:
Allergens: e.g. animal dander, pollen
Exercise
Cold air
Respiratory tract infection Environment
Tobacco smoke
Drug induced: NSAIDs especially Aspirin,-blockers
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Classification of asthma
Quick reliefof
symptoms
term-Longcontrol
SymptomsStage
Short acting
2 agonists.
No
medication2 /weekMild
intermittent
Short acting2 agonists.
dose ofICS
>2 /weekbut not daily
Mild
persistent
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Classification of asthma
Quick relief
ofsymptoms
term-Long
control
SymptomsStage
Short acting
2 agonists.
to medium
dose of ICS&long acting
2 agonists.
Daily
symptoms
Moderate
persistent
Short acting
2 agonists.
dose of ICS
&oral CS&long acting
2 agonists
Cont.
symptomsThroughout
the day
Severe
persistent
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THE GOALS OF ASTHMA MANAGEMENT
Achieve and maintain control of symptoms
Prevent asthma exacerbations
Maintain pulmonary function as close tonormal as possible
Avoid adverse effects from asthmamedications
Prevent development of irreversible airflowlimitation
Prevent asthma mortality
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Approaches to treatment
Determine precipitating factors & avoid
them if possible
Bronchodilator to reverse the
bronchospasm
Anti-inflammatory agents to inhibit or
prevent the inflammatory components & the
hyperactivity of the bronchi
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A. Bronchodilators:
They are 1st line drug & include:
1.2-receptor agonists (1st choice of
bronchodilators)
2.Methylxanthines3.Muscarinic receptor antagonists
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1.Selective 2-agonists:
These drugs are usually given by inhalation(preferable) of aerosol, powder, or nebulizedsolution or may be given orally or by injection (foremergency)
2 categories of 2 adrenoceptor agonists: Short Acting Agents: Salbutamol, Terbutaline.
They are usually used on "as needed" basis tocontrol symptoms of acute attack
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Long Acting Agents: Salmeterol, Formeterol
They are not used "as needed" but are given regularly
twice daily as prophylaxis (prevent bronchospasm at nightor with exercise)
S/Es:The unwanted effects of 2-adrenoceptor agonists result
from systemic absorption
1.Tachycardia
2.Tremor
3.Hyperglycemia
Salbutamol oral side effects :taste changes, teeth
discoloration
Salmeterol oral side effects: Dental pain, throat dryness
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2. Methylxanthines:
These are 3 pharmacologically active naturally
occurring substances: Theophylline, Caffeine &
Theobromine.
The one which employed in clinical medicine is
Theophylline & Aminophylline(Theophylline salt)
Theophylline is given orally in sustained-release
preparation; Aminophylline can be given I.V. infusion
(slowly) to treat status asthmaticus.
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Has narrow therapeutic index (10-20mg/mL) so: Dont combine oral & I.V.
Before giving I.V. Theophylline, always ask if the patientis already taking Theophylline orally
Monitor for signs of toxicity: vomiting, headache,
tachycardia
Obtain Theophylline serum concentration
Clinical uses of theophylline:
1. as second line drug, in addition to steroids, in patients
whose asthma does not respond to 2 agonists.
2. Intravenously in acute sever asthma.
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S/Es:
1.CNS excitation, tremor, nervousness
2.Tachycardia.3.Nausea & vomiting.
D/D interaction: possible theophylline toxicity (metabolism) if used with
erythromycin,ciprofloxacin,clarithromycin.
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3.Muscarinic Antagonists:
The main compound used specifically as anti-asthmatic is Ipratropium
It is quaternary derivative given by aerosol, it is notwell
absorbed thus the possibility of systemic S/E isminimal
S/Es:1.Cough
2.Dryness of mouth
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Clinical uses:
1.As bronchodilator in some patients with
bronchospasm precipitated by 2-receptorantagonists
2.As an adjunct to 2-agonists & steroids
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B. Anti-inflammatory agents:
1.Glucocorticoids (corticosteroids)
Inhaled corticosteroids like:
a. Beclomethasone
b. Budesonide
c. Fluticasone
Oral like: Methylprednisolone.
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Indication for inhaled glucocorticoids:
For asthmatic patients who are inadequate controlled
with other regimes
Indication for systemic glucocorticoids:
1.For chronic asthma & severe rapidly deteriorating asthma,a short course of oral glucocorticoids is indicated,
combined with inhaled steroids to reduce steroids oral
dose.
2.In status asthmaticus, hydrocortisone is given I.V.
followed by oral steroids.
f
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Pharmacokinetics of Inhaled
Corticosteroids
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S/Es:
Inhaled corticosteroids S/Es are minimal:
1. Oral candidiasis
2.Dysphonia
These are less likely to occur if spacing devices are
used
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Effect of
Spacer onThe delivery
Of an inhaled
aerosol
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Oral & systemic corticosteroids S/Es are:
1.hypertension.
2.hyperglycemia..etc
3.Osteoporosis4.Cushinglike syndrome: moon face, acne,
increased body hair growth, edema,
redistribution of fats
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2.Cromoglycate & Nedocromil
MOA: Stop the release of mediators from mast cells inthe bronchi
They are given by inhalation prophylactically
They are effective in antigen-induced, exercise-induced& irritant induced asthma
S/Es: bitter taste ,irritation of the pharynx & larynx
These agents should never replace inhaled
corticosteroids or quick relief2 agonists as the
mainstay of asthma therapy.
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3.Leukotriene Modifiers
Leukotrienes are substances, produced
by inflammatory cells which causespasm of bronchial muscle
Leukotrienes receptor antagonistsinclude: Montelukast, Zafirlukast
Zileuton is a selective inhibitor for 5-
lipoxygenase enzyme so it production
of Leukotrienes
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Clinical uses:
These agents are use prophylactically
Used mainly as add on therapy for mild tomoderate asthma.
Inhibit exercise-induced bronchospasm &
aspirin induced asthma
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Sites of
action ofleukotriene
modifying
drugs
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4. Omalizumab
Is a recombinant DNA- derived monoclonal
antibody that is selectively binds to human IgE
prevents binding of IgE to mast cells & basophils decreases release of mediators following
allergen exposure
Use:
allergic asthma not well controlled bycorticosteroids
severe persistent asthma
M f S A h i
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Management of Status Asthmaticus
Severe acute asthma is a medicalemergency requiring hospitalization
Treatment
1.Ensure adequate hydration of the patient ifnecessary by infusion as this will preventthe sputum become sticky
2.Oxygen, inhalation of Salbutamol in oxygen
given by nebulizer3.In severe attack Salbutamol 250mcg or
Aminophylline 250mg can be given I.V.
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4.Hydrocortisone 200mg I.V. every 6 hours
followed by Prednisolone 60mg orally for 2weeks
5.Antibiotics if definite evidence of infection.
NO sedatives of any kind e.g.
Diazepam
Exposure to antigen
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Exposure to antigen(Dust, pollen, etc)
avoidance
Antigen & IgEon mast cell
cromolyncorticosteroids
ziluton
Mediators(Leukotrienes, Cytokines)
2agonists CorticosteroidsTheophylline CromolynMuscarinic antagonists Leukotriene antagonists
Early response Late response:(Bronchoconstriction) (inflammation)
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Clinical implications: Acute bronchoconstriction can occur during dental
treatment, have bronchodilator available.
Ensure that bronchodilator inhaler is present at eachdental appointment.
Be aware that sulfites in local anesthetic withvasoconstrictor can precipitate acute asthma attackin susceptible individuals.
Inhalants can dry oral mucosa, anticipatecandidiasis, increased plaque levels & increased
caries.
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Oral health educations:
If chronic dry mouth occurs, recommend homefluoride therapy & use nonalcoholic oral health careproducts.
Rinse mouth with water after bronchodilator to
prevent dryness.
Teach the patient to rinse mouth & garglevigorously with water after inhaled corticosteroids to
minimize the potential candidiasis.
Encourage daily plaque control procedures foreffective self-care.
T f C h
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Treatment of Cough
Cough is a normal physiological reflexes that free the
respiratory tract of accumulated secretions &removes particulate matter & environmental irritants
Types of cough:
1.Productive cough
Effectively expels secretions & foreign substances
Generally should not be suppressed
2 U d ti h
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2.Unproductive cough
It is also called irritant cough
No materials come out from respiratory tract
when coughing, but we feel of pain & dryness &
something irritating
Interferes with sleep or exhausts the patient
It should be suppressed
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Treatment: Antitussives: Drugs that suppress cough
1.Peripherally Acting
a. Demulcents
Used as: lozenges, syrups
Soothing coat the pharynx They protect underlying mucosa from irritation
b. Water aerosol inhalation
They sooth the lower part of pharynx
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2. Centrally ActingThese are used to suppress cough when peripherally acting
methods were not effective
a. Morphine Related Drugs (such as: Codeine)
b. Dextromethorphan
c. Antihistamines
Oral health education:
Inform the patients that syrup contain sugar & to usefluoride products to prevent dental caries.
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Drugs that facilitate productive cough
1.Expectorants
They encourage & facilitate productive cough byincreasing the volume & decreases viscosity of
bronchial secretion
E.g.: Bromohexine
2.Mucolytics
They facilitate the productive cough by reducing the
sputum viscosity
E.g.: Acetylcysteine