PH2113 - Pulmonary Flashcards
Why do you need to use a preventer and a reliever for the treatment of asthma instead of one?
Preventors only stop inflammation they do not affect smooth muscle contraction.
What is the equation for airflow in lungs?
How does the body increase airflow to help symptoms of airflow resistance during an asthma attack?
Airflow = pressure gradient/resistance.
Increase and external intercostal muscle- greater pressure difference to overcome increased resistence.
How does an asthma attack affect the lungs- symptomology of asthma?
Bronchoconstriction from contraction of smooth muscle.
Release of inflammatory response and mucus production.
Explain how sensitisations causes asthma?
- Allergen recognised by foreign protein by dentritic cell.
- Dentritic cell migrate to lymph nodes where allergen is displayed on T-cell.
- T-cell differentiate to Th2 lymphocyte.
- Activation of B-cells generate IgE and binds to allergen.
- Fc region of IgE binds to high affinity receptors on mast cells causing inflammation.
What are the different phenotypes in asthma- give examples.
Intrinsic/allergen: pollen, mould.
Extrinsic/non-allergen based: weather, aspirin and exercise.
Explain the early phase of asthma.
What mediators cause 1. bronchoconstriction & eosinophil release.
2. prostaglandin release?
- Activation of degranulation of mast cell by allergen-induced cross linking IgE.
- Mast cells release humoral inflammatory mediated- histamine causing bronchoconstriction.
- Activation of phospholipase A2 triggers Arachidonic acid cascade for inflam mediators. eg. CysLT1 and cyclo-oxygenase COX1 &2.
How does affects of asthma cause late response?
Eosinophils continue to cause inflammation in late phase- increase vascular permeability leading to oedema causing further narrowing. Build up of mucus.
What happens structural in lungs during airway remodelling? x4
Thicker airway reducing blood flow.
Muscus occlusion of airway.
Increased expsoure of underlying sensory nerves.
Hypertropy and hyperplasia.
How do relievers generally work?
Reduce cytosolic Calcium for smooth muscle contraction- activation of cAMP and activate beta-2-adrenoceptors.
What is the treatment for acute COPD exabations?
SABA, Corticosteriods, Doxapram.
What are the 2 lung function parameters: which is for obstructive and restrictive?
Lung capacity- how much air the lungs can hold. Airflow- how quickly air can be removed from the lungs.
What is the mechanism of action for beta-2 adrenoceptors?
- Binds to Gs.
- Gs activated adenyl cyclase to generate cAMP.
- cAMP activated protein kinase to reduce cytosolic Ca2+.
- PKA reduces IP3 preventing release of Ca2+store. Limited contraction from myosin filaments.
- Na/K increases K for the cell to be hypopolarised.
What is the MOA for xanthines?
Inhibit phosphodiesterase to increase cAMP which decreases ATP to limit inflammation.
What is the MOA of Muscarinic receptor antagonists?
Inhibit M3 receptors for bronchoconstriction to be released by ACh from parasympathetic nerves causing bronchodilation.
Why are Muscarinic receptor antagonists used for COPD more?
Parasynthetic tone needed for action.
Why is muscarinic receptor antagonist limited when increasing dose?
Limit receptor sensitivity.
How do corticosteriods work?
Why do they take time to work?
- Drug diffused and binds to cortisol receptors.
- translocate in nucleus causing transcription of anti-inflammatory gene IL-10.
- Reduce transcription of pro-inflamm genes eg. cyclo-oxygenase and nitric oxide synthase.
What are the factors that affect glucocorticoid potency?
Affinity- higher binding affinity = lower dose needed.
Lipophilicity- access inside of cell- increased lipohilicty increases potency.
What is the MOA for leuktriene receptor antagonists?
Block cysteinyl leukotriene receptor 1- needed for contraction of C4 and D4 for inflammation.
What is the MOA of chromones?
Inhibit mast cells reducing inflammation.
What is the MOA for biologics in asthma?
IL-5?
Omalizumab?
use of anti-bodies: IL-5: reduce recruitment and activation limits remodelling and asthma attacks.
Omalizimab: Target IgE b;acl Fc receptor to prevent cross-linking.
What are differences in symptoms between asthma and COPD?
COPD: persistent, increased breathlessness, chesty cough where symptoms get progressively worse. No genetic link.
Asthma: Episodic breathlessness, episodes of wheezing, genetic link.
What is the first line treatment for COPD?
SAMA or SABA.
What is the typical treatment for COPD and Asthma?
LABA and ICS.
