Pharmacology of the Respiratory Tract

7/30/2019 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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4


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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

23


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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

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Pharmacology of the Respiratory Tract

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