Download Asthma

Drugs Used in Asthma
Dr. Sasan Zaeri
(PharmD, PhD)
Department of Pharmacology
1
Asthma
A chronic inflammatory disorder of bronchial
airways that result in bronchospasm in
response to external stimuli (pollen, cold air,
tobacco smoke etc.)
2
Symptoms of asthma
• Asthma produces recurrent episodic attack of
– Acute bronchoconstriction
– Shortness of breath
– Chest tightness
– Wheezing
– Rapid respiration
– Cough
3
Pathophysiology
of Immunologic
Asthma
4
5
http://link.brightcove.com/services/player/bcpid236059233?bctid=347806802
6
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 )
7
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
•
•
•
2-agonists
Antimuscarinics
• Corticosteroids
•Mast cell stabilizers
• Leukotrienes antagonists
Methylxanthines
•Anti-IgE monoclonal antibody
8
- adrenoceptor agonists
• Mechanism of Action
 Direct
2 stimulation  stimulate adenyl cyclase
 Increase cAMP  bronchodilation
9
Classification of  agonists

Non selective  agonists
 epinephrine

- isoproterenol
Selective 2 – agonists (Preferable)
 Salbutamol
(Albuterol)
 Terbutaline
 Salmeterol
 Formeterol
10
Nebulizer
Inhaler
11
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)
12
• Adverse effects of selective 2 –agonists
– Skeletal muscle tremor
– Tachycardia and arrhythmia
– Tolerance and tachyphylaxis
13
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
14
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
15
Methylxanthines
Theophylline - Aminophylline
•
Mechanism of Action

Phosphodiestrase (PDE) inhibition   cAMP 
bronchodilation
 Adenosine
receptor antagonists
16
17
• Uses

Second line drug in asthma (theophylline in nocturnal
asthma)

For status asthmatics (aminophylline is given as slow
infusion)
18
• Side Effects

CVS: arrhythmia

GI: nausea & vomiting, ↑ gastric acid secretion

CNS: tremors, nervousness, insomnia,
convulsion

Kidney: ↑renal blood flow, weak diuretic action
19
• 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
20
Anti - inflammatory Agents
(control medications / prophylactic therapy)
By reducing inflammation, they reduce bronchial
hyper-reactivity and bronchospasm
21
Anti-inflammatory Agents

Glucocorticoids

Leukotrienes antagonists

Mast cell stabilizers

Anti-IgE monoclonal antibody (Omalizumab)
22
Glucocorticoids
• Mechanism of action
– Inhibition of phospholipase A2 → ↓ prostaglandin
and leukotrienes
– Mast cell stabilization →↓ histamine release
– Upregulation of β2 receptors
23
24
Routes of administration

Inhalation

Budesonide, Fluticasone, Beclomethasone

Less side effects

Oral

Prednisolone

Parenteral

Hydrocortisone, Methylprednisolone

Status asthmaticus (IV infusion)
25
Glucocorticoids
 Are not bronchodilators
 Given as prophylactic medications, used alone or
combined with beta-agonists
26
Side effects of systemic corticosteroids
–
–
–
–
–
–
–
–
–
–
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
27
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)
28
Mast cell stabilizers
Cromolyn - Nedocromil

Act by stabilization of mast cell membrane

Have poor oral absorption

Given by inhalation
29
Mast cell stabilizers
Not bronchodilators
Not effective in acute attack of asthma
Prophylactic anti-inflammatory drugs
Children respond better than adults
30
Uses

Prophylactic therapy in asthma especially in children

Allergic rhinitis

Conjunctivitis
Side effects

Bitter taste

minor upper respiratory tract irritation (burning sensation)
31
Leukotrienes antagonists

Leukotriene B4
 chemotaxis of neutrophils

Leukotrienes C4 and D4
 bronchoconstriction
32
Leukotriene receptor antagonists
Zafirlukast, Montelukast

Taken orally

Are bronchodilators


Are NOT effective to relieve acute attack of asthma
Have anti-inflammatory action
33
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)
34
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
35
Summary
36