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CR1 > Pharmacology of the Airways > Flashcards

Pharmacology of the Airways Flashcards

1
Q

How many divisions are there in the airways?

A

23

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2
Q

Which cells are involved in carrying out the autonomic nervous system in the airways?

A

Lung effector cells

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3
Q

What is the parasympathetic signal pathway from the brain to the lungs?

A

Central nervous system
Vagus nerve/parasympathetic nerve
Parasympathetic ganglion (in the trachea and conducting bronchi)
Post ganglionic fibres
Submucosal glands, blood vessels and airway smooth muscle

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4
Q

What is the sympathetic signal pathway from the brain to the lungs?

A

CNS
Sympathetic ganglion
Sympathetic nerve
Airway smooth muscle

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5
Q

What is the adrenal signal pathway from CNS to lungs?

A

CNS
Adrenal medulla
Bronchial vessel
Airway smooth muscle

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6
Q

Where are cell bodies of the preganglionic and postganglionic fibres located?

A 
Preganglionic = brainstem
Postganglionic = embedded in walls of bronchi and bronchioles
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7
Q

What does stimulation of postganglionic cholinergic fibres cause?

A
  • Bronchial smooth muscle contraction mediated by M3 muscarinic ACh receptors on ASM cells
  • Increased mucus secretion mediated by M3 muscarinic ACh receptors on gland (goblet) cells
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8
Q

What does stimulation of postganglionic noncholinergic fibres cause?

A

Bronchial smooth muscle relaxation mediated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)

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9
Q

What is the mechanism for bronchoconstriction of the airways?

A
  • Acetylcholine (ACh), binds to G-protein (Gq)-coupled muscarinic M3 receptors = ↑ phospholipase C (PLC) = ↑ inositol 1,4,5-trisphosphate (IP3)
  • IP3 binds to ligand-gated IP3 receptors (IP3Rs) on the endoplasmic reticulum (ER) = Ca2+ release into the cytoplasm
  • ↑ intracellular Ca2+ = Ca2+ binding to calmodulin (CaM) & subsequently myosin light chain kinase (MLCK) = catalytically active (Ca2+)4-CaM-MLCK complex = which then phosphorylates (P) light chain of myosin (MLC20) = actin–myosin cross-linking & smooth muscle contraction
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10
Q

How does the sympathetic system affect bronchodilation?

A
  • Sympathetic NS
    o Human airway innervation is sparse
    o No functional evidence for direct innervation of airway smooth muscles
    o However, sympathetic nerves regulate bronchial blood flow & to a lesser extent mucus secretion
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11
Q

Asthma and COPD are caused by the chronic inflammation is which cells?

A 
Eosinophils
Monocytes
Epithelial cells
Macrophages
Neutrophils
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12
Q

What type of airway remodelling is caused by COPD?

A

Bronchoconstriction
Mucus hypersecretion
Emphysema

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13
Q

What are the types of bronchodilators?

A
  • Short- or Long-acting muscarinic antagonists (SAMA & LAMA) block the binding of acetylcholine (ACh) to M3 muscarinic receptor = inhibit smooth muscle cell contraction
  • Short- or Long-acting Beta2-adrenergic receptor agonists (SABA/LABA) bind to beta2-adrenergic receptor & induce a cascade of signal transduction events = smooth muscle relaxation
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14
Q

What are the treatments for asthma?

A

Regular preventer
Initial add-on therapy
Additional add-on therapies
High dose therapies
Continuous or frequent use of oral steroids
Reliever: SABA as required
LABA is used as an add-on therapy to ICS (inhaled corticosteroids)

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15
Q

What are the treatments for COPD?

A 
Group A (0-1 moderate exacerbations): a bronchodilator
Group B (0-1 moderate exacerbations): a long-acting bronchodilator (LABA or LAMA)
Group C (> 2 moderate exacerbations or >1 leading to hospitalisation): LAMA
Group D (> 2 moderate exacerbations or >1 leading to hospitalisation): LAMA or LAMA+LABA or ICS+LABA
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16
Q

What is the treatment goal of inhaled corticosteroids?

A

Treatment goal = reduce underlying inflammation

17
Q

How does an IgE-mediated allergy occur?

A

2 stages: sensitisation and provocation
APC process antigen → Major histocompatibility complex II molecules present antigen to naïve T cells → promotes development of TH2 type of T cell → TH2 cells prduce IL-4 & IL-13 → B cells produce IgE → IgE bids to mast cells → sensitised mast cells → exposure to allergen → IgE crosslinking & mast cell degranulation → release of mast cell mediators

18
Q

How are mast cells involved in asthma?

A

Allergen exposure and mast cells - lead to production of mediators and cause inflammation
Role in bronchoconstriction and mucus hypersecretion
Lead to airway limitation

19
Q

Summarise the pharmacology of the airways.

A
  • Activation of Parasympathetic nerves leads to airway bronchoconstriction
  • Bronchodilators: Muscarinic antagonists & beta2-adrenergic receptor agonists
  • Bronchodilators & ICS commonly prescribed in asthma & COPD to improve lung function & reduce airway inflammation
  • Allergy to aeroallergens (dust, pollen etc) may worsen asthma symptoms via an IgE-mediated mechanism

CR1 (23 decks)

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