L3 - Drugs Influencing Airway Resistance Flashcards
What is the equation for resistance?
R α 1/r^4
Where in the respiratory tract is resistance the greatest?
In the large and medium sized bronchi.
What types of innervation does the smooth muscle in the airways have?
NANC innervation (non andronergic non cholinergic innervation).
Parasympathetic innervation/
What is the effect of stimulation of NANC innervation of the smooth muscle in the airways?
- Bronchodilation.
- But in asthma substance P may cause bronchoconstriction.
What is the effect of stimulation of parasympathetic innervation of the smooth muscle in the airways?
Bronchoconstriction.
What receptors are stimulated in the parasympathetic innervation of the smooth muscle in the airways?
M3 receptors.
What are the transmitters of NANC innervation?
Nitric oxide (NO) and vasoactive intestinal peptide (VIP).
Where are β2 receptors found?
Which ligand binds to β2 receptors?
What is the effect of activation of β2 receptors?
- β2 receptors are found on airway smooth muscle.
- Circulating adrenaline binds to β2 receptors.
- β2 receptors cause:
- Bronchodilation,
- Inhibition of mast cell activity,
- Promotion of muco-ciliary escalator activity.
What is degranulation?
Where does it occur?
- A cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles known as granules.
- Occurs in granulocytes and mast cells.
How do mast cells contribute to asthma pathology?
- Mediators released by degranulation of mast cells cause bronchoconstriction.
- e.g. Histamine, platelet activating factor and leukotrienes.
What effect does CO2 have on the diameter of the airways? Why is this useful?
- CO2 causes bronchodilation.
- Important for ventilation-perfusion matching.
How does parenchyma help lower airway resistance?
- Airways are embedded in lung parenchyma.
- Parenchyma provides ‘radial traction’ to keep the airways open.
- Inflation increases radial traction and reduces airway resistance.
- Parenchyma also ensures alveolar interdependence.
How is airway resistance increased in COPD?
Loss of both radial traction and alveolar interdependence.
List 3 signs and symptoms of asthma.
1 - Episodes of bronchoconstriction.
2 - Bronchial hypersensitivity - airway mucosa inflammation.
3 - Increased airway secretions.
What is ipratropium?
- An inhaled muscarinic antagonist that is an analogue of atropine.
- Blocks the bronchoconstricting action of ACh.
How do β2 agonists cause bronchodilation?
- Bind to β2 receptors.
- β2 receptors are G proteins with a Gs alpha subunit, so stimulate the AC / cAMP / PKA pathway.
- Intracellular Ca2+ decreases, increasing bronchodilation and reducing inflammation.
List 2 β2 agonists.
1 - Salbutamol (short acting).
2 - Salmeterol (long acting).
What is a PDE inhibitor?
- An inhibitor of phosphodiesterase.
- Inhibition causes increase in cAMP pathways.
- Increase in cAMP pathway increases bronchodilation and reduce inflammation.
What are methylxanthines?
Give an example of a methylxanthine.
List 4 side effects of theophylline.
- PDE inhibitors.
- e.g. Theophylline.
- Side effects include: 1 - Headaches. 2 - Restlessness. 3 - Abdominal symptoms. 4 - Arrhythmias.
List 3 side effects of β2 agonists.
1 - Tachycardia.
2 - Tremor.
3 - Airway hyper-responsiveness.
What is omalizumab and how does it work?
- A monoclonal anti-IgE antibody.
- Reduces circulating IgE, reducing mast cell degranulation and inflammation.
- Used in severe allergic asthma.
List 3 symptoms of aspirin-induced asthma.
1 - Rhinorrhea.
2 - Nasal congestion.
3 - Sinusitis.
What is a biochemical difference in patients that are aspirin intolerant to those that are not?
- Aspirin intolerant patients upregulate 5-lipoxygenase in response to taking aspirin.
- 5-lipoxygenase is involved in the leukotriene pathway.
What are H1 receptors?
A histamine receptor that plays a role in inflammation.
What is ketotifen and how does it work?
- A H1 receptor antagonist.
- Acts as an anti-inflammatory after 6-12 weeks treatment.
- Reduces reliance on steroids.
What is a prophylactic treatment?
A preventative treatment.
What is sodium cromoglicate / cromolyn and how does it work?
- A prophylactic treatment.
- Inhibits the release of inflammatory mediators from mast cells.
Name a side effect of ketotifen.
Drowsiness (10-15% patients).
List 3 side effects of sodium cromoglicate / cromolyn.
1 - Coughing.
2 - Wheezing.
3 - Dry throat.
What is zileuton and how does it work?
- A leukotriene formation antagonist.
- Targets the leukotriene pathway.
- Inhibits 5-lipoxygenase, halting the pathway.
What are montelukast, pranlukast and zafirlukast? What do they do?
- Leukotriene receptor antagonists.
- Used in severe chronic and exercise-induced asthma.
- Causes bronchodilation, decreases mucus secretion and reduces inflammation.
What is the result of leukotrienes binding to leukotriene receptors (CysLT1 receptors)?
Bronchoconstriction.
What initiates the leukotriene pathway?
The leukotriene pathway is an inflammatory response.
How does atropine reduce airway resistance?
It antagonises the parasympathetic innervation to the smooth muscle (it is a muscarinic antagonist).
How do β2 agonists cause inflammation?
- β2 receptors are found on inflammatory and immune cells.
- stimulation of these receptors decreases their activity.
