BM322 Block D

Asthma Characteristics

Asthma involves chronic inflammation driven by eosinophils, mast cells, and neutrophils. It includes hyper-responsiveness of smooth muscle to constrictors like acetylcholine and hypo-responsiveness to relaxants like adrenaline.

Allergic Asthma Immune Response

Allergic asthma involves allergens taken up by dendritic cells, leading to Th2 cell proliferation, IgE production, and mast cell activation, causing bronchoconstriction.

Asthma Remodelling

Asthma remodelling includes structural changes like epithelial damage, goblet cell hyperplasia, smooth muscle hypertrophy, and basement membrane thickening, which are irreversible over time.

Muscarinic Receptors in Asthma

The muscarinic M3 receptor in asthma causes airway contraction through IP3 and calcium pathways, sustained by PKC inhibition of MLCP, and Rho activation.

Airway Muscle Proliferation

Asthma involves airway muscle hypertrophy and hyperplasia stimulated by growth factors, leading to autocrine loops and paracrine signaling for proliferation.

Neuronal Imbalance in Asthma

Asthmatics have reduced adrenergic receptors, increased cholinergic drive, and defects in cholinergic innervation, resulting in hyper-responsiveness of smooth muscle in the bronchial tree.

C-Fibres in Asthma

C-fibres in asthma respond to irritants/allergens, leading to increased vagal tone, acetylcholine release, and reflex bronchoconstriction.

COPD Overview

COPD is a chronic progressive disorder with airflow obstruction, irreversible airflow limitation, and changes in mucus gland thickness, alveolar walls, and lung function.

Chronic Bronchitis Vs

Chronic bronchitis involves mucus production, while emphysema results from alveolar wall breakdown, reducing gas exchange surface area.

Cellular COPD Mechanisms

COPD mechanisms involve TGF beta-induced fibroblast proliferation, protease inhibitor inhibition by oxidants, and alpha 1 anti-trypsin deficiency leading to tissue damage.

Immunological Components in COPD

COPD involves innate responses, Th1/Th17 signaling enhancement, CD8+ cell damage, and M2 macrophage predominance, impacting healing and immune responses.

Lipophilic group

Allows for longer binding to the receptor, giving a dissociation time of over 300 minutes, resulting in a 12-hour action time compared to salbutamol, requiring fewer doses.

Desensitisation

Loss of response to the agonist over time due to phosphorylation of the occupied receptor by a specific receptor kinase (GRK), leading to internalisation of the receptor.

Beta adrenoceptor agonists

Activate Gs, promoting adenylyl cyclase stimulation, cAMP formation, PKA activation, which inhibits MLCK, promotes calcium efflux, inhibits the MPK pathway, leading to bronchial smooth muscle relaxation and bronchodilation.

Anti-Muscarinics

Used in COPD, ipratropium is a non-selective blocker, tiotropium acts primarily on M3 receptors, relaxing airway smooth muscle and reducing mucus production.

Steroid Drugs

Glucocorticoids reduce inflammation in asthma and COPD, used prophylactically, act by binding to responsive elements of genes (GRE), inhibiting inflammatory genes, and increasing lipocortin expression.

Synergy

Interaction between beta 2 agonists and steroids, enhancing cellular response, increasing beta 2 receptor expression, and glucocorticoid receptor expression.

Leukotriene Inhibitors

Zafirlukast and montelukast inhibit leukotriene effects, reducing bronchoconstriction, bronchial reactivity, and mucous hypersecretion.

Xanthines

Theophylline and profylline act as adenosine receptor antagonists, blocking adenosine's inhibitory action on adenylyl cyclase, promoting smooth muscle relaxation.

PDE Inhibitors

Theophylline inhibits PDEs, blocking cAMP and cGMP breakdown, raising intracellular cAMP levels, promoting relaxation.

Biologics

Antibody-based treatments targeting cytokines and leucocytes, such as anti-IL13 (Tralokinumab, lbrikizumab) and anti-IL5 (Mepoluzimab), used in severe disease states.