Bronchial Asthma

One of the commonest chronic diseases

Inhalation Therapy : A Major Landmark

 

Bronchial Asthma

Chronic disorder with intermittent episodes of bronchospasm

- Dyspnoea
- Wheeze
- Cough

 

Aetiology

* Heredity
* Allergy
* Drugs
* Psychological
* Infections
* Cold
* Exercise

 

Types of Bronchial Asthma

* Extrinsic Asthma
* Intrinsic Asthma

Important Lung Function Tests

- FEV1
- PEFR

 

Clinical Features

- Dyspnoea
- Cough
- Wheezing

Status Asthmaticus

 

 

Principles of Management of Asthma

* Control symptoms
* Maintain normal pulmonary function
* Avoid triggers
* Prevent / manage exacerbations
* Avoid adverse effects of drug therapy
* Patient education
* Reduce mortality

 

Management of Asthma

1. Prevention
2. Immunotherapy
3. Drug Therapy
- inhalation
- oral
- parental

Drug Therapy of Bronchial Asthma
- Important Agents

 

Inhalation Therapy

* Direct drug delivery to respiratory tract
* Major milestone in asthma therapy
* First line of treatment today

 

 

 

 

 

 

 

Types of Inhalation Therapy

Metered dose inhalers - MDI
* Most widely used form of inhalation therapy
* Drug delivery as aerosol
* Needs coordination between actuation and inhalation

Rotahalers
* Involve inhalation of dry powder
* For patients who cannot coordinate actuation & inhalation
* Unsuited for breathless patient
* Require good inspiratory flow rate

Types of Inhalation Therapy (contd.)

Nebulisers
* Normal breathing is adequate
* Expensive
* Regular maintenance required
* Risk of transmitting air-borne infections

 

Advantages of Inhalation Therapy

* Drug delivery directly to desired site
* Greater efficacy
* Lower doses - better tolerability

 

Metered Dose Inhalers (MDIs)
Meters, aersolises and delivers drug

* Based on principle of propellant system
* Drug-propellant mixture in a cannister
* On actuation, drug released as an aerosol
* Inhalation must be coordinated with aerosol release

 

 

Proper Inhalation Technique is Necessary!

* High aerosol cloud velocity - 100 k. m.p.h.
* Aerosol likely to hit the throat
* Smaller particles can reach the lower respiratory tract, where action is desired
* Larger particles likely to be deposited in the throat (hence wasted)
* Coordinating inhalation with actuation increases the quantity of drug reaching the lower respiratory tract
* Patient education improves coordination
* ‘Cold Freon’ effect

 

Spacer Devices

* Plastic container serving as reservoir into which MDI releases drug
* Spacer slows down the aerosol and allows particles to remain suspended
in the device
* Inhalation need not be coordinated with actuation
* Useful in patients who cannot coordinate inhalation with actuation
* Helps to maximise lung delivery and minimize throat deposition
* Lower doses are effective

Commonly Used Agents in InhalationTherapy

Beta Receptor Agonists

* Stimulate beta-2 receptors in bronchi
---> bronchodilation
* Selective beta agonists avoid cardiac adverse effects
* Short acting -- Salbutamol, terbutaline;
Long acting -- Salmeterol
* May be used alone or with other drugs e.g., steroids

Xanthines
(e. g. Theophylline, Aminophylline)

- Phosphodiesterase inhibition
- Adenosine receptor antagonism
- Mast cell stabilisation
- Improvement of diaphragmatic contractility
- Prostaglandin inhibition
- Alteration of intracellular Ca++ concentration
- Immunomodulation

 

Corticosteroids
(e. g. beclomethasone, budesonide)

Potent anti-inflammatory effect
* Inhibit chemical mediators
* Inhibit inflammatory cells, e. g., eosinophils
* Reduce vascular permeability
* Increase sensitivity of beta receptors

 

 

Mast Cell Stabilisers
(e. g. ketotifen, nedocromil)
* Prevent release of inflammatory mediators

Anticholinergics
(e. g. ipratropium)
* Inhibit action of acetylcholine --> bronchodilation

Inhalation Therapy for Asthma
(Based on NHBL guideline)

Salbutamol

First line anti-asthmatic therapy
* Quick onset; short duration of action
* Suited for intermittent attacks and as rescue medication

Actions
* Selective beta-2 agonist
* Effective bronchodilation
* Avoids cardiac adverse effects

Pharmacokinetics
* Bronchodilation within 10 min
* Action lasts for 6 hours
* Only a small portion (10%) that goes into the lungs appears as free drug in systemic circulation
* Excreted in urine (80%) and faeces (20%) within 24 hours

 

Salbutamol (contd.)

Indications
- Bronchial asthma
- Chronic bronchitis & emphysema

Dosage:

* Prevention of asthma & relief of acute episodes	1-2 inhalations	3-4 times daily
* Prevention of exercise induced asthma	2 inhalations	15 min before exercise
* Total daily dose	16-20 inhalations
* Children	1 inhalation	3 - 4 times daily ( can be increased to 2)

(for packs providing 100 mg salbutomal (per dose)

 

Salbutamol (contd.)

Tolerability
* Well tolerated
* Smaller drug doses - avoids tremor and other side effects of oral therapy
* Has been used throughout pregnancy without ill effects
* Excreted in breast milk - no ill effects on child

Contraindications
* Hypersensitivity

Beclomethasone Dipropionate

Potent Antiinflammatory
* First line corticosteroid therapy for asthma
* Controls hyper-reactivity and inflammation
* May be used alone / together with beta agonists
* Improvement in respiratory functions within a week
* Allows elimination / reduction of oral steroids

Beclomethasone (contd.)

Pharmacokinetics:
* Only a fraction of administered dose reaches lungs
* Rapid inactivation of swallowed drug in liver

Tolerability:
* Generally safe
* Occasionally throat irritation, dysphonia, sore throat, dryness of mouth
* Candidal infection of throat/mouth may occur

Pregnancy and Lactation:
* Inadequate evidence of safety in pregnancy
* Potential benefits to be weighed against hazards
* Low potential for significant levels in breast milk

Precautions:
* Caution in transfer from oral to inhaled corticosteroid
* Substitution of inhaled drug for oral corticosteroid can cause withdrawal symptoms

 

Beclomethasone (contd.)

Indications:
Prophylaxis of bronchial asthma

Dosage:
Adult & Children over 12 years.
* Starting dose, 2-4 inhalations or 4 inhalations, 3 - 4 times daily twice daily
* Mild asthma, 200 - 600 mcg
* Moderate asthma 600 - 1000 mcg
* Severe asthma 1000 - 2000 mcg

Children 4-12 years.
1-2 inhalations 3-4 times dailyor400 mcg per day undivided doses

(for packs providing 50 mcg, 100 mcg and 250 mcg beclomethasone per dose)

 

Salmeterol

Long acting selective Beta-2 agonist
* Bronchodilation within 10-20 minutes persisting for 12 hours
* Suitable for long term administration
* Useful in nocturnal & exercise induced asthma
* Can be used with short acting bronchodilator / steroid

Salmeterol (contd.)

Pharmacokinetics:
* Peak plasma concentration in 5-15 minutes
* Extensively metabolised by hydroxylation
* Eliminated within 72 hours

Tolerability:
* Well tolerated
* Adverse effects similar to salbutamol

 

Salmeterol (contd.)

Indications:
* Long term treatment of mild to severe asthma
* Nocturnal asthma and exercise induced asthma

Pharmacokinetics:
* 2 inhalations twice daily(50 - 100 mg twice daily)

(for packs providing 25 mg salmeterol per dose)

 

 

Budesonide

Newer corticosteroid with specific benefits
* High ratio of topical anti-inflammatory to systemic activity
* Potential to become a first-line treatment

Pharmacokinetics:
* Extensive first-pass metabolism

Tolerability:
* Well tolerated even on long term use
* Minimum systemic adverse effects
* Local effects-hoarseness, sore throat, cough

 

Budesonide (contd.)

Indications:
* Management of adult and childhood asthma

Dosage:
* Must be individualised
* Initial recommended dose : 400 - 1600 mcg per daydivided into 2 - 4 administrations
* Maintenance dose: 200 - 400 mcg

Salbutamol + Beclomethasone

Bronchodilator + Corticosteroid combination for Moderate to Severe asthma
* Benefits of two time-tested agents
* Patients not responding to single ingredients benefit from combination therapy
* Compliance and convenience

 

Salbutamol + Beclomethasone (contd.)

Indications
* Moderate to severe asthma

Warnings and Precautions:
* Not for acute attacks but for long-term therapy
* Regular reassessment of patients advisable

Dosage:
* Adults : 2 inhalations 3 - 4 times a day
* Children : 1-2 inhalations 2-4 times daily

(for packs providing salbutamol 100mcg and beclomethasone diproprionate 50 mcg per dose)

 

Salient Features
Salbutamol

* Salbutamol - time tested agent
* Beta-2 stimulation - bronchodilation
* Selectively avoids cardiac adverse effects
* Quick onset, short duration
* For immediate relief form bronchospasm

 

Salient Features
Salmeterol

* Long acting beta-2 agonist
* Convenient twice daily dosing
* Suitable for long term use, nocturnal & exercise induced asthma
* Avoids cardiac effects
* 50 mcg salmeterol similar to 200 mcg salbutmol

 

 

Salient Features
Beclomethasone Dipropionate

* Beclomethasone - time tested corticosteroid
* Useful for preventing attacks
* Reduces inflammation, airway hyper-responsiveness and allergic response
* Can be used alone or with beta-2 agonists
* Enhances response to bronchodilators
* Safer alternative to oral steroids

 

Salient Features
Budesonide

* Newer corticosteroid
* Predominant local action
* Less systemic availability- avoids systemic adverse effects

 

Salient Features
Salbutamol + Beclomethasone

* Combination of two time-tested agents
* For moderate to severe asthma not responding to single agents
* Convenience of fixed dose combination
* Comprehensive asthma control