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What is asthma
What is asthma?

What is COPD?

What is asthma

  • Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive airway disease (COAD), is a group of diseases characterised by limitation of airflow in the airway that is not fully reversible. COPD is the umbrella term for chronic bronchitis and/or emphysema. It is most often due to tobacco smoking[1] but can be due to other airborne irritants such as coal dust or solvents.

Chronic Bronchitis

Chronic bronchitis is defined in clinical terms as a cough with sputum production on most days for 3 months of a year, for 2 consecutive years.[6]

Chronic bronchitis is hallmarked by the increased number (hyperplasia) and increased size (hypertrophy) of the mucus-secreting (goblet) cells of the airway. This, along with enlargement of the mucous gland, results in an increase in production of mucus which contributes to the airway obstruction. Microscopically there is infiltration of the airway walls with inflammatory cells, particularly neutrophils. Inflammation is followed by scarring and remodelling that thickens the walls resulting in narrowing of the small airway. Further progression leads to an abnormal change (metaplasia) in the nature of the tissue along with further thickening and scarring (fibrosis) of the lower airway. The consequence of these changes is a limitation of airflow. [7]


Main article: Emphysema

Emphysema is defined histologically as the enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls.[6]

The enlarged air sacs (alveoli) of the lungs reduces the surface area available for the movement of gases during respiration. This can cause breathlessness in severe cases. The exact mechanism for the development of emphysema is not understood, although it it known to be linked with smoking and age.

Historically what therapeutic agents have been used
Historically, what therapeutic agents have been used?

  • Ephedrine, as part of the Chinese medicine Ma Huang, has been used in the treatment of respiratory diseases for over 5000 years

  • Ephedrine is now known to act indirectly, by releasing endogenous catecholamines, resulting in bronchodilation

  • In 1900, Solis-Cohen showed that orally administered adrenal extract was beneficial in asthma.


  • Initially, subcutaneous injections of epinephrine were used, followed by a nebulized epinephrine solution.

  • Epinephrine is one of the most potent vasopressor (i.e. causes constriction of the blood vessels and corresponding rise in blood pressure) drugs known.

  • Epinephrine affects respiration primarily by relaxing the bronchial muscle.

  • Epinephrine is rapidly metabolized by COMT, primarily in the liver.

Can we make an asthma drug with less side effects and longer lasting
Can we make an asthma drug with less side effects, and longer lasting?

  • Clues:

  • It is known that the 2 receptor is the target for relaxation of bronchial smooth muscle.

  • Epinephrine has approx. equal affinity for both  and  receptors

  • However norepinephrine has greater affinity for the  receptors

  • This indicates that placing an alkyl group on the nitrogen leads to an increase in selectivity for the -receptors.

What is asthma

Equal selectivity for longer lasting?

Both and -receptors

Greater selectivity for


Perhaps, still greater selectivity for -receptors could be

Generated by appending larger alkyl substituent on nitrogen

An improvement
An improvement! longer lasting?

  • Isoprenaline was synthesized by German chemists in the 1940’s

  • It had less cardiovacular side effects than adrenaline

  • Became the most widely used inhaled treatment for asthma for the next 20 years.

Further improvements needed
Further improvements needed longer lasting?

  • Needed an agent which was longer lasting, more resistant to COMT

  • Needed an agent which was more selective for the 2 receptors in the lung and less selective for the 1 receptors of heart.

Arrives salbutamol
Arrives Salbutamol longer lasting?

  • Tert-butyl group renders salbutamol more selective for 2

  • Hydroxymethyl group (in place of OH) renders salbutamol resistant to COMT

  • Remains the most widely used anti-asthma drug in the world

Salbutamol longer lasting?

  • Salbutamol (INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and COPD.Salbutamol sulphate is usually given by the inhaled route for direct effect on bronchial smooth muscle. This is usually achieved through a metered dose inhaler (MDI), nebuliser or other proprietary delivery devices (e.g. Rotahaler or Autohaler). In these forms of delivery, the effect of Salbutamol can take place within 5 to 20 minutes of dosing. Salbutamol can also be given orally or intravenously. However, some asthmatics may not respond to these medications as they will not have the required DNA base sequence in a specific gene.Salbutamol became available in the United Kingdom in 1969 and in the United States in 1980 under the trade name Ventolin.

What is asthma

Salmeterol longer lasting? is a long-acting beta2-adrenergic receptor agonistdrug that is currently prescribed for the treatment of asthma and chronic obstructive pulmonary disease COPD. It is currently available in both dry-powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs).

It is a long acting beta-adrenoceptor agonist (LABA), usually only prescribed for severe persistent asthma following previous treatment with a short-acting beta agonist such as salbutamol and is prescribed concurrently with a corticosteroid, such as beclometasone. The primary noticeable difference of salmeterol to salbutamol is that the duration of action lasts approximately 12 hours in comparison with 4ミ6 hours of salbutamol.

What is asthma

BRONCHODILATORS, ADRENERGIC (Inhalation) longer lasting?*

In the U.S.-

Adrenalin Chloride 3

Airet 1

Alupent 8

Arm-a-Med Isoetharine 6

Arm-a-Med Metaproterenol 8

AsthmahalerMist 3

AsthmaNefrin 3

Beta-2 6

Brethaire 12

Bronkaid Mist 3

Bronkaid Suspension Mist 3

Bronkometer 6

Bronkosol 6

Dey-Lute Isoetharine6

Dey-Lute Metaproterenol 8

Foradil 5

Isuprel 7

Isuprel Mistometer 7

Maxair 9

Maxair Autohaler 9

Medihaler-Iso 7

microNefrin 3

Nephron 3

Primatene Mist 3

Proventil 1

Proventil HFA 1

S-2 3

Serevent Diskus 11

Vaponefrin 3

Ventolin 1

Ventolin HFA 1

Ventolin Nebules 1

Ventolin Rotacaps 1tolin Rotacaps 1

In Canada-

Alupent 8

Apo-Salvent 1

Berotec 4

Bricanyl Turbuhaler 12

Bronkaid Mistometer 3

Foradil 5

Gen-Salbutamol Sterinebs P.F. 1

Isuprel 7

Isuprel Mistometer 7

Maxair 9

Novo-Salmol 1

Oxeze Turbuhaler 5

Pro-Air 10

Serevent 11

Serevent Diskhaler 11

Serevent Diskus 11

Vaponefrin 3

Ventodisk 1

Ventolin 1

Ventolin Nebules P.F. 1

Ventolin Rotacaps 1tolin Rotacaps 1

This information applies to the following medicines:

1.Albuterol (al-BYOO-ter-ole)‡§

2.Bitolterol (bye-TOLE-ter-ole)*†

3.Epinephrine (ep-i-NEF-rin)‡

4.Fenoterol (fen-OH-ter-ole)*

5.Formoterol (for-MOH-ter-ol))‡§

6.Isoetharine (eye-soe-ETH-a-reen)†‡

7.Isoproterenol (eye-soe-proe-TER-e-nole)‡

8.Metaproterenol (met-a-proe-TER-e-nole)‡

9.Pirbuterol (peer-BYOO-ter-ole)

10.Procaterol (proe-KAY-ter-ole)*

11.Salmeterol# (sal-ME-te-role)*

12.Terbutaline (ter-BYOO-ta-leen)