Respiratory Pharmacology 1
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What is the endogenous bronchodilator and where does it act?
Circulating Adrenaline acting at beta 2 adrenergic receptors.
What is the endogenous bronchocontrictor and where does it act?
Acetlycholine acting on M3 receptors causes bronchoconstriction and increases secretion of mucus.
Definition of Asthma
- -A respiratory disease, often caused by allergens
- -Involves reversible constriction of the bronchioles
- -Difficulty in breathing, particularly exhaling
Characteristics of asthma?
- 1. Intermittent attacks of coughing, wheezing and difficulty breathing.
- 2. Increased airway resistance, leading to a decreased force of expiratory volume
- 3. The symptoms can be treated but the disease cannot be cured.
What is bronchial hyper reactivity?
- A characteristic of Allergic Asthma.
- Abnormal sensitivity to stimuli which results in bronchoconstriction.
- May be initiated by exposure to allergens, but once established, can be triggered by various stimuli eg cold air.
- The result is bronchoconstriction and inflammation of the airways.
What happens when an allergen is detected?
- TH2 cells become activated and procuce 3 types of cytokines
- 1. Resulting in release of IGE
- 2. Differentiation and activation of eosinophils
- 3. Increase in IGE receptor expression on mast cells and eosinophils.
When the allergen is inhaled again, what happens?
It cross links the IGE molecules on the mast cells, triggering degranulation with the release of histamine which is a bronchoconstrictor. Released granule proteins also cause damage to the epithelium, increasing hyper reactivity. These factors cause an asthma attack.
What happens in the Immediate stage of an Asthma attack?
- The allergen binds to IGE on mast cells, causing them to degranulate and release spasmogens which cause a bronchospasm.
- Chemotaxins and chemokines are released, and leukocytes are recruited, contributing to the late phase of the attack.
What happens in the Late phase of an asthma attack?
There is an infiltration by TH cells, eosinophils and monocytes (from the immediate phase). These cause the release of mediators such as leukotrienes, adenosine and NO, which cause airway inflammation, airway hyperreactivity and bronchospasm. Toxic proteins such as ECP and EMBP are also released. These cause endothelial damage which contributes to airway hyperreactivity. The overall effect is wheezing, coughing, and a difficulty in breathing.
What are the changes that occur in the bronchiole with severe chronic asthma?
- Infiltration of inflammatory cells
- Thickened basement membrane
- Dilated blood vessels
- Mucus plug, containing damaged epithelial cells
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