Wednesday, 29 February 2012

Asthma pathophysiology and types

Asthma is a chronic inflammatory disorder causes due to immune responses leads to swelling and narrowing of airways causes wheezing, shortness of breath, chest tightness and coughing particularly at night or in early morning. It can be classified according to sign and symptoms, severity, forced expiration volume in 1 second (FEV1) and peak expiration flow rate.

Pathogenesis of Asthma

It is an immunological disorder causes reversible air flow obstruction. Pathogenesis of this disorder can be divided into three steps.
1. Stimuli from external stimulus: Stimuli can be given by the following types-
a) Allergens (dust)
b) Medication: aspirin, penicillin
c) Exercise
d) Hormonal changes
All these are the stimulus which starts the immune responses leads to the development of Th-2 lymphocytes predominant immune response associated with atrophy lead to IgE-mediated inflammation. T-helper cells like cytokines participate to contribute inflammation of airways lead to hyperactive responses of IgE.
2. Bronchoconstriction: During asthma airways tract react with allergens produces mucus in large amount leads to difficulty in breath
3. Bronchial inflammation: After the immune response occurs mucus producing cells grow large and produces more mucus as cell mediated arm of immune system is activated and airways become highly inflamed.
Acetylcholine is the parasympathetic immunomodulator present in the smooth muscles of airways control the bronchoconstriction and production of mucus when this process get highly activated lead to asthma. Vagal tone is increased in the airways inflammation associated with asthma leads to exaggerated acetylcholine release. Acetylcholine controls this whole process by acting on muscrinic receptors m2 and m3. When parasympathetic activity increased in airways lead to inflammation so anticholinegic therapy is used which acts as bronchodilators.

Types of Asthma

We can classify asthma in different order which keep you in different category which helps the doctors to prescribe you different treatment depending on the category type.

1) Depending on the participation of allergens, asthma is divided into following types-
A. Atropic (Extrinsic) asthma
B. Non-atropic (intrinsic) A.

Atropic asthma

This type of asthma is also known as allergic asthma may be due to the continues exposure to allergens like smoke, dust mites, mold, animal dander and is mainly occur due to the immune responses.

Non-atropic asthma

In this type of asthma there is not any involvement of allergens but may be due to other reasons. Depending on this it is of various types:
a) Cough variant asthma: In this type of asthma there is involvement of cough allergens with other symptoms of asthma.
b) Occupational asthma: This kind of asthma affects the people working in the area of high pollution due to the shortness of breath.
c) Exercise induced asthma: It is due to the condition of bronchoconstriction during the exercise.
d) Nocturnal asthma: amount of breath inhaled by a person is measured in FEV1Which is decreased by at least 15% from bed time includes the other symptoms of asthma which may disrupt the sleep and may wake up you from sleep.
e) Steroid resistant asthma: Peoples who regularly inhaled glcocorticoids may become unresponsive to that normal dose include other symptoms.
f) Health condition mimic asthma: Asthma may leads to other problems included cardiac arrhythmia, vocal cord dysfunction.
g) Child hood asthma: It is occur in children due to the hormonal changes.
h) Adult orient asthma: it is occur after the age of 20 more in women as compare to men due to plastic, pollution, mites.
i) Bronchial asthma: difficulty in breathing and wheezing, mucus of airways become narrow, thick mucus produced which causes irritation.

2. Classification of asthma based on severity:
A. Intermittent( moderate asthma)
B. Mild persistent( acute asthma)
C. Severe persistent( life threatening)

Thursday, 2 February 2012

Mast cell stabilizers used in the treatment of asthma

Mast cell stabilizers are also becoming popular in the treatment of asthma. They act by inhibiting the release of mediators such as histamine from the mast cells and hence prevent the asthma attack. This over secretion of mediators from the mast cells is one of the chief reasons of asthma.

Individual mast cell stabilisers for asthma

1. Sodium Cromoglycate (Cromolyn Sodium) - Sodium cromoglycate is the first drug used in this class. Cromolyn sodium is synthetic derivative of chromone. It acts by preventing the release of asthmatic mediators like histamine, leukotrienes, interleukins, PAF etc. from mast cells.

Sodium cromoglycate does not affect the antigen-antibody reaction and hence it has no effect if used at the time of asthmatic attack. Sodium cromoglycate is effective in the prevention of bronchospasm caused by any reason. However, long term use of Sodium cromoglycate decreases the response of inflammatory cells.

Sodium cromoglycate is orally ineffective drug and so most preferably it is administered as aerosol preparation. Sodium cromoglycate is used in the treatment of bronchial asthma, allergic rhinitis and allergic conjunctivitis.

The main adverse effects of Sodium cromoglycate include bronchospasm, throat irritation and cough can occur in some patients. Rare side effects are nasal congestion, headache, dizziness, arthralgia, rashes and dysuria.

2. Nedocromil Sodium – Nedocromil Sodium is another chromone derivative which is almost similar in action to the cromoglycate. The only difference with the Sodium cromoglycate is that it is more potent than the same and hence requires lesser dose.

3. Ketotifen – This is the only orally active mast cell stabilizer. Primarily this drug is antihistaminic (H1) and slightly cromoglycate type activity. Ketotifen chemically is non chromone derivative and primarily used for the prophylaxis of asthma.
The main side effects of ketotifen include sedation, dry mouth, dizziness, nausea, weight gain etc.

Note- This article is written for the purpose of providing you the basic knowledge of the topic and should not be taken as for prescription.

Other suggested readings for the treatment of asthma-
1. Treatment of asthma by sympathomimetic drugs.
2.Herbal drugs used for the treatment asthma

Sunday, 29 January 2012

Treatment of bronchial asthma by sympathomimetic drugs

Sympathomimetic or adrenergic agents are drug of choice for bronchodilation. The most probable mechanism of action of adrenergic drugs is that they stimulate beta receptors. This stimulation result in increased cAMP production in bronchial muscle cell and hence relaxes the bronchial muscles. Increased cAMP production in the mast cell also decreases the mediator release due to antigen antibody reactions. The adrenergic drugs should be used with up most care in the hypertensive patients and patients receiving digitalis. The most preferred route for administration of sympathomimetics is through inhalation.

Individual sympathomimetics for the treatment of asthma

1. Adrenaline- Adrenaline is sympathomimetic drug with alpha, beta1 and beta2 agonist activity. The antiasthmatic action of adrenaline is due to its strong affinity to beta2 receptor. As this drug is not selective in its action because it also associated with rise of blood pressure and cardiac stimulation so adrenaline is no more drug of choice for asthma.

2. Ephedrine- Ephedrine is also sympathomimetic drug with alpha, beta1 and beta2 agonist activity. It causes slow bronchodilation which lasts from 3 to 5 hours. Ephedrine is now seldom used in the treatment of asthma due to its low efficacy and side effects. Earlier ephedrine was used in combination for the treatment of mild and moderate asthma.

3. Isoprenaline- Isoprenaline is beta1 and beta2 agonist. The bronchodilation caused by the isoprenaline last for 1 to 2 hours. This drug was removed from the market due to its induced tachycardia due to beta1 stimulation.

4. Orciprenaline- The action of orciprenaline is similar to isoprenaline but it is slightly more selective beta2 agonist than isoprenaline. Orciprenaline is an orally effective antiasthmatic and have a bronchodilating effect ranging from 3 to 4 hours. The emergence of new more selective beta2 agonist has resulted in the withdrawal of this drug from the market.

5. Salbutamol (Albuterol) - Salbutamol is highly selective beta2 agonist. This drug is safer and long lasting than isoprenaline but have similar efficacy. The major side effects of salbutamol are cardiac arrests, palpitation, restlessness, nervousness, throat irritation and ankle edema.

6. Terbutaline- Terbutaline has almost similar mechanism action and pharmacological properties as of salbutamol. At present, salbutamol and terbutaline are the most popular drugs for asthma. They are administered through inhalation. It is seen in most of the cases that both of the drugs doesn't produce any response after some time.

7. Salmeterol- Salmeterol is the most recently used beta2 agonist. The drug is given twice a day for nocturnal asthma. Salmeterol is most effective when given concurrently with glucocorticosteroids. Salmeterol also has the same problem of unresponsiveness for asthma after prolonged use of the same.
Suggested readings-
1.Mast cell stabilisers used in the treatment of asthma.
2.Herbal drugs used for the treatment asthma