Respiratory Pharmacology
Bronchial Asthma
‫الربوالشعبى‬
Bronchial Asthma
Inflammation
Bronchial
Hyper-responsiveness
Reversible
airway
obstruction
AIRWAY HYPER-RESPONSIVENESS
Bronchi constrict easily to a wide range of specific or
nonspecific stimuli (Triggers) that are too weak to affect
non- asthmatics
Shortness of breath, wheezing ‫يزيق‬, chest tightness &
cough
Causes
Genetic
Environmental
‫ النسيج‬,‫سمنت‬4‫ ا‬, ‫مصانع الرخام‬, drugs, cold
weather, exercise
Home dust, ‫العث‬mites
‫بد التهوية و الشمس‬4 mites
Chronic obstructive pulmonary
disease‫زمن‬D‫نسدادي ا‬4‫مرض الرئة ا‬
2 diseases
Chronic bronchitis + mucus
Emphysema
Irreversible
Asthma reversible by drugs
Drug Therapy of Bronchial Asthma
As needed
Daily
1. Short-acting b 2-agonists (rapid; 1st
1. Corticosteroids (CS)
choice). salbutamol
2. Long acting β2-agonists
2. Antimuscarinics
3-Methyl xanthines (theophylline)
.
+CS,( not alone).
Salbutamol
If the patient chronic give oral drugs
If the patient acute
give IV or inhalation drugs
Bronchodilators
Relieve acute bronchospasm
Antimuscarini
c
Β2 agonist
Muscarinic
receptors
adenylyl
cyclase
Ton
e
Vagus nerve
β2receptors
cAMP
Tone
Adenosin
e
receptors
Block
Ton
e
Adenosine
Antimuscarinic Drugs (atropine xxx)
(Ipratropium Bromide)
BLOCK M3 RECEPTORS IN BRONCHIAL MUSCULATURE →
BLOCK VAGALLY-MEDIATED BRONCHOSPASM AND
MUCUS SECRETION
Uses: 1. Bronchodilator of choice when 2- agonists & theophylline are CI
(e.g. cardiac & thyrotoxic patients).
2. Adjuvant to 2- agonists or theophylline in A. severe asthma
Disadvantages: 3T, H
1. Tolerance: block M2 R
2. Delayed onset of action
↑ ACh release
↓ its own effect.
(Ipratropium Bromide)
I‫تروب‬4‫ابن عم ا‬
Quaternary not cross blood brain barrier
Atropine…….sedation, dryness,, hotness, constipation
SADHc not present
More selective to bronchi
No systemic action as atropine
Ipratropium Bromide
With combivent beta 2 agonist
‫ مع بعض‬I‫ثن‬4‫ا‬
cAMP
Phosphodiesterase
Enzyme 3,4
GAMP
Antiinflammatory
Bronchodilation
Relaxation of smooth muscles
Blocks adenosine
receptors
Aminophylline
is
a
drug
combination of theophylline and
ethylenediamine in a ratio of 2 to
1. it serves to solubilize the
active
ingredient theophylline.
I.V. infusion to avoid tachycardia
no inhalation due to irregular absorption
Theophylline
For Chronic asthma give
Quibron T-SR tablet
theophylline tablet
For acute asthma give
aminophylline I.V. infusion 1520 minutes
no inhalation due to irregular
absorption
Uses
1. Bronchial asthma: 2nd line drug to β2-agonists
2. COPD :Chronic Obstructive Pulmonary Disease
Other uses xanthine's
1. CNS stimulation
2-for migraine
•Cafergot for migraine due to
vasoconstriction due to synergism
ergotamine and caffeine
cerebral
between
Adverse Effects
(Limit its use)
1. CNS stimulation
Insomnia – Anxiety -Tremors –
convulsions
headache
2. GIT: ↑HCl ,Gastric irritation
Peptic ulcer xxx
3. CVS: Hypotension, arrhythmias and
cardiac arrest
arrhythmias xxx
↑HC
l
Precautions
1- If used orally, it is taken with food to avoid gastric ulcer
2- If used IV, it is injected very slowly to avoid cardiac arrest
3- Plasma level should be monitored (narrow therapeutic index)
4- Adjust the dose in age extremes, liver disease, HF, heavy smokers and
if used with enzyme inducers or inhibitors
Antiinflammatory
Long Term Control
of
Persistent Asthma
Corticosteroids
Mainstay of Therapy
Immunosuppressants
Antiinflammatory
Potentiate β2 agonists
(↓downregulation of β2 R ↓tolerance).
CS Preparations
Inhalation: acute asthma
Beclomethazone (↓ systemic adverse efects)
2. Oral:
Prednisolone or dexamethasone.
3. I.V.:hydrocortisone (it is used in emergency).
Acute asthma : Hydrocortisone injection for emergency
Or inhalation bechlo Beclomethazone
Adverse Effects
Oropharyngeal candidiasis
Due to Cortisone immune suppressant
2. Salt and water retention, hypokalemia ‫ياكل موز و موالح‬
3. edema. Give diuretic
Minimized by:
Gargling & spitting
Drug Therapy of Cough
peripheral cough receptor in bronchi
‫ترسل رسائل الى‬
Cough centers in medulla (central)
•‫الى‬
‫يعطى اشارة‬
respiratory muscle in alveoli
contraction
‫مدة الكحة‬
•Less
than 3 weeks……………acute cough
•More
than 8 weeks …………… chronic cough
•More
than 3 weeks and less than 8 weeks ……………
subacute cough
•Dry
or wet
Drug Therapy of Cough
Dry (non-productive cough):
Treated by:
Antitussives
(Cough Suppressants)
Productive cough:
Treated by:
Mucolytics and
expectorants
Antitussives
Central
Antitussives
1. Opioid antitussives:
inhibits cough center
a- Codeine & Hydrocodone :
b- Dextromethorphan:
Less addictive -no respiratory depression –
no constipation.
2. Antihistamines (1st G)
(Diphenhydramine)
Peripheral
Antitussives
1.
Volatile oils
(menthol and camphor):
Protect irritant receptors by a mucin
layer (demulcents).
2. Benzonatate:
- local anesthetic effect on irritant
receptors in respiratory mucosa.
Thin film of water steam or
volatile oils on bronchi wall
Demulcent effect ‫تلطف‬
Tincture benzoin compound
‫صنغ جاوة‬
Expectorants (1st line)
liquefy bronchial secretion (↑volume &↓viscosity)
Facilitate sputum removal by
cough
-Guaifensin: guaiac tree gastric irritant; given with a full glass of water.
-Aromatic expectorants: volatile oils in water vapor e.g. tolu .
-Nauseant: e.g. syrup ipeca.
-Alkaline: Na+ acetate or Na+ citrate.,
-
Guaifensin
Na+ & K+ Iodides
Adverse Effects of iodides:
1. Respiratory irritation (CI: acute bronchitis & asthma).
2. Gastric irritation
3. Hypersensitivity and allergy.
4. Iodism: excessive secretions of exocrine glands (lacrimal, salivary…metallic taste).
others
Ammonium chloride
Guafia
Ipeca
Mucolytics (2nd Line)
They ↓ viscosity of bronchial secretion without affecting the amount; potentiating
expectorants e.g.:
‫دوب البلغم ولم يؤثر علي الكمية‬
1- Bromhexine (Bisolvon)
2- ambroxol
3.Acetylcysteine, carbocysteine
Adverse Effects of Mucolytics:
Gastric irritation
Hypersensitivity
Bronchospasm (acetylcysteine).
Water vapor inhalation is
an excellent expectorant
and mucolytic.
Questions???