Transcript Asthma

Drugs Used in Asthma
Dr. Sasan Zaeri
(PharmD, PhD)
Department of Pharmacology
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Asthma
A chronic inflammatory disorder of bronchial
airways that result in bronchospasm in
response to external stimuli (pollen, cold air,
tobacco smoke etc.)
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Symptoms of asthma
• Asthma produces recurrent episodic attack of
– Acute bronchoconstriction
– Shortness of breath
– Chest tightness
– Wheezing
– Rapid respiration
– Cough
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Pathophysiology
of Immunologic
Asthma
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http://link.brightcove.com/services/player/bcpid236059233?bctid=347806802
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Aims of Anti-asthmatic Drugs
• To relieve acute episodic attacks of asthma
(bronchodilators, quick relief medications)
• To reduce the frequency of attacks, and
nocturnal awakenings (anti-inflammatory drugs,
prophylactic or control therapy )
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Anti-asthmatic Drugs
Bronchodilators
(Quick relief medications)
Anti-inflammatory Agents
(control medications or
prophylactic therapy)
treat acute episodic attack of
asthma
reduce the frequency of attacks
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2-agonists
Antimuscarinics
• Corticosteroids
•Mast cell stabilizers
• Leukotrienes antagonists
Methylxanthines
•Anti-IgE monoclonal antibody
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- adrenoceptor agonists
• Mechanism of Action
 Direct
2 stimulation  stimulate adenyl cyclase
 Increase cAMP  bronchodilation
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Classification of  agonists

Non selective  agonists
 epinephrine

- isoproterenol
Selective 2 – agonists (Preferable)
 Salbutamol
(Albuterol)
 Terbutaline
 Salmeterol
 Formeterol
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Nebulizer
Inhaler
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Selective 2 –agonists
Short acting ß2 agonists (salbutamol, terbutaline)


Drugs of choice for acute attack of asthma
Long acting ß2 agonists (salmeterol, formoterol)


Used for nocturnal asthma (long acting relievers)

Combined with inhaled corticosteroids to control asthma
(decreases the number and severity of asthma attacks)
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• Adverse effects of selective 2 –agonists
– Skeletal muscle tremor
– Tachycardia and arrhythmia
– Tolerance and tachyphylaxis
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Muscarinic antagonists
Ipratropium

Act by blocking muscarinic receptors

Given by aerosol inhalation

Quaternary derivatives of atropine
 Do

not enter CNS
Does not diffuse into the blood
 Minimal
systemic side effects
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Effects

Inhibit bronchoconstriction and mucus secretion

Less effective than β2-agonists
Uses


Main choice in chronic obstructive pulmonary
diseases (COPD)
In acute severe asthma combined with β2agonists & steroids
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Methylxanthines
Theophylline - Aminophylline
•
Mechanism of Action

Phosphodiestrase (PDE) inhibition   cAMP 
bronchodilation
 Adenosine
receptor antagonists
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• Uses

Second line drug in asthma (theophylline in nocturnal
asthma)

For status asthmatics (aminophylline is given as slow
infusion)
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• Side Effects

CVS: arrhythmia

GI: nausea & vomiting, ↑ gastric acid secretion

CNS: tremors, nervousness, insomnia,
convulsion

Kidney: ↑renal blood flow, weak diuretic action
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• Drug interactions

Metabolized by Cyp P450 enzymes in liver
 Enzyme
inducers e.g. phenobarbital, rifampin, tobaco smoke
→ ↑metabolism of theophylline
 Enzyme
inhibitors e.g. erythromycin→
↓ metabolism of theophylline
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Anti - inflammatory Agents
(control medications / prophylactic therapy)
By reducing inflammation, they reduce bronchial
hyper-reactivity and bronchospasm
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Anti-inflammatory Agents

Glucocorticoids

Leukotrienes antagonists

Mast cell stabilizers

Anti-IgE monoclonal antibody (Omalizumab)
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Glucocorticoids
• Mechanism of action
– Inhibition of phospholipase A2 → ↓ prostaglandin
and leukotrienes
– Mast cell stabilization →↓ histamine release
– Upregulation of β2 receptors
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Routes of administration

Inhalation

Budesonide, Fluticasone, Beclomethasone

Less side effects

Oral

Prednisolone

Parenteral

Hydrocortisone, Methylprednisolone

Status asthmaticus (IV infusion)
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Glucocorticoids
 Are not bronchodilators
 Given as prophylactic medications, used alone or
combined with beta-agonists
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Side effects of systemic corticosteroids
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Adrenal suppression
Growth retardation in children
Osteoporosis
Fluid retention, weight gain, hypertension
Hyperglycemia
Susceptibility to infections
Glaucoma
Cataract
Fat distribution, wasting of the muscles
Psychosis
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Inhalation therapy has less side effects
– Oropharyngeal candidiasis (thrush)
– Dysphonia (voice hoarseness)
Withdrawal
– Abrupt stop of corticosteroids should be avoided
and dose should be tapered (adrenal insufficiency
syndrome)
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Mast cell stabilizers
Cromolyn - Nedocromil

Act by stabilization of mast cell membrane

Have poor oral absorption

Given by inhalation
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Mast cell stabilizers
Not bronchodilators
Not effective in acute attack of asthma
Prophylactic anti-inflammatory drugs
Children respond better than adults
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Uses

Prophylactic therapy in asthma especially in children

Allergic rhinitis

Conjunctivitis
Side effects

Bitter taste

minor upper respiratory tract irritation (burning sensation)
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Leukotrienes antagonists

Leukotriene B4
 chemotaxis of neutrophils

Leukotrienes C4 and D4
 bronchoconstriction
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Leukotriene receptor antagonists
Zafirlukast, Montelukast

Taken orally

Are bronchodilators


Are NOT effective to relieve acute attack of asthma
Have anti-inflammatory action
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Uses
Prophylaxis of



Mild to moderate asthma

Aspirin-induced asthma

Antigen and exercise-induced asthma
Can be combined with glucocorticoids (low dose of
glucocorticoids can be used)
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Anti-IgE monoclonal antibody
Omalizumab
 A monoclonal antibody directed against human IgE
 It binds to the IgE on sensitized mast cells and prevents
activation by asthma triggers and subsequent release of
inflammatory mediators
 Expensive-not first line therapy
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Summary
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