Pharmacology of the Airways Flashcards
What nervous system predominates in the control of airway smooth muscle?
Parasympathetic
How does the parasympathetic nervous system cause bronchoconstriction?
Acetylcholine acting on muscarinic M3 receptor
Describe how the sympathetic nerves affect the control of airway smooth muscle tone
- Innervate blood vessels and glands
- Can inhibit parasympathetic ganglia to prevent acetylcholine release
- Adrenaline inhibits release of mediators from mast and mucocilliary cells
Name 2 chemicals which relax airway smooth muscle
- VIP
2. Nitrous oxide
Name 2 chemicals which constrict airway smooth muscle
- Substance P
2. Neurokinin
What is bronchial asthma?
Chronic inflammatory disease of airways that causes acute bronchospasm
Describe the events in asthma from chronic inflammation to acute bronchospasm
- Chronic inflammatory response
- Mast cell and eosinophil mediator release
- Damage to epithelial layer / increased irritability
- Acute bronchospasm
Name 2 symptoms of asthma which accompany bronchospasm
- Mucous secretion
2. Blood vessel leak
What are 2 influences leading to an asthma attack asthma?
- Genetic predisposition (hyper-reactive airways)
2. Environmental exposure (trigger)
Name 5 examples of asthma attack triggers
- Upper RTIs
- Allergens (dust, fur)
- Irritants (smoke)
- Medication
- Exercise
Name a medicine which can cause asthma attacks
Aspirin
How can aspirin cause an asthma attack?
- Inhibits prostaglandin synthesis from leukotriene
- Increases leukotriene levels in body
- Leukotriene can act as an irritant
Name 2 phases of an asthma attack
- Immediate phase (response to triggers)
2. Delayed phase
Name 2 chemicals released during the immediate phase of an asthma attack
- Spasmogens
2. Chemotaxins
Name 4 spasmogens released during an asthma attack
- Acetylcholine
- Histamine
- LTC₄
- D₄
Name 3 physiological symptoms of the release of spasmogens
- Wheezing
- Coughing
- Bronchospasm
Name 2 chemotaxins released during an asthma attack
- LTB₄
2. Cytokines
What is the physiological outcome of the release of chemotaxins during an asthma attack?
Influx of inflammatory cells
What 2 physiological processes occur during the delayed phase of an asthma attack?
- Activation of inflammatory cells
2. Mediator release
Name 2 main classes of drug which are used to treat asthma
- Bronchodilators (treat wheezing)
2. Anti-Inflammatory drugs (prophylactic drugs)
Name 4 types of bronchodilators
- β₂ adrenoceptor agonists
- Muscarinic antagonists
- Leukotriene antagonists
- Xanthines
Name 2 examples of short acting β₂ adrenoceptor agonists
- Salbutamol
2. Terbutaline
Name an example of a long acting β₂ adrenoceptor agonist
Salmeterol
What is the mode of action of β₂ adrenoceptor agonists
- Agonises β₂ adrenoceptor
- G protein produces cAMP as a second messenger
- cAMP-dependent protein kinase becomes activated
- Proteins phosphorylation causes bronchodilation
Describe how β₂ adrenoceptor agonists are usually administered?
Inhalation as reduces systemic dose (side-effects) but retains effectiveness
Name 3 additional benefits of β₂ adrenoceptor agonists other than bronchodilation
- Reduce mast cell mediator release
- Inhibit vagal tone
- Promote mucous clearance
Name 5 adverse effects of β₂ adrenoceptor agonists
- Muscle tremor
- Hypokalaemia
- Tachycardia
- Arrhythmias
- Tolerance
Why does tolerance develop for β₂ adrenoceptor agonists?
Excessive use causes downregulation of β₂ adrenoceptors in the airway so there is a less marked dilatory effect
How does muscarinic antagonists function?
Block bronchoconstrictor and mucus-secreting effects of parasympathetic neurotransmitter acetylcholine mediated via muscarinic M3 receptors
What types of bronchospasm are muscarinic antagonists particularly effective for?
Bronchospasm induced by irritant stimuli
Describe 2 second messengers present in PLC-β signalling pathway
- PR3 causes increased calcium release from sarcoplasmic reticulum
- DAG activates protein kinase C which phosphorylates proteins which modifies calcium handling
Name a short acting muscarinic antagonist
Ipratropium bromide
Name an established long acting muscarinic antagonist
Tiotropium bromide
Name 3 newer long acting muscarinic antagonist
- Umeclidinium
- Aclidinium
- Glycopyrronium
How are muscarinic antagonists usually administered?
Inhalation as reduces systemic dose (side-effects) but retains effectiveness
Name 4 side effects of muscarinic antagonists
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
Name a drug which is a leukotriene synthesis inhibitor
Zileuton
Name 3 targets of zileuton
- LTB₄
- LTC₄
- D₄
Name a drug which acts as cysLT₁ receptor antagonist
Montelukast
Name 3 specific types of asthma drugs targeting leukotrienes are useful
- Exercise induced asthma
- Aspirin induced asthma
- Responses to inhaled allergens
Name 3 side effects of drugs targeting leukotrienes
- Headache
- GI upset
- Abdominal pain
- Churg-Strauss syndrome (rare)
Name an example of a xanthine drug
Theophylline
What is theophylline used for?
Reserve drug for difficult to control patients who do not respond adequately to β₂ agonists
Name 2 ways which theophylline may be administered
- Orally
2. Slow IV infusion
Describe the mode of action of theophylline
- Inhibits cyclic nucleotide phosphodiesterase
- Prevents hydrolysis of cyclic ring in cAMP
- Higher levels of cAMP persist for longer in cytoplasm
- Prolongation of cAMP-dependent signalling
Name 4 useful effects of theophylline
- Relaxes bronchial smooth muscle
- Some anti-inflammatory effects
- Stimulates respiratory centre in brain
- Prevents diaphragm fatigue
What is a major consideration for a person prescribed theophylline?
Narrow therapeutic window means plasma concentrations must be monitored
What 3 types of drugs regularly used to prevent inflammation during prophylactic treatment for asthma?
- Glucocorticosteroids
- Xanthines
- Drugs targeting leukotrienes
Name 2 drugs used rarely in to prevent inflammation during prophylactic treatment for asthma?
- Cromolyn sodium
2. Nedocromil sodium
Name a type of drug used to resolve established inflammation during anti-inflammatory treatment for asthma?
Glucocorticosteroids
Name 3 inhaled glucocorticosteroids
- Beclometasone
- Budasonide
- Fluticasone
Name an oral glucocorticosteroid
Prednisolone
Name an intravenous glucocorticosteroid
Hydrocortisone
How do glucocorticosteroid function?
Increase β₂ receptor expression / response
Name 4 types of molecules inhibited by inhaled corticosteroids leading to the reduction of inflammation
- Cytokines
- Enzymes
- Peptides
- Adhesion molecules
Name 3 ways corticosteroids reduce inflammation
- Reduce chemotaxins
- Reduce synthesis of spasmogenic mediators
- Reduce endothelium prostaglandin release
Name 2 side effects of corticosteriods
- Oropharyngeal candidiasis
2. Sore throat
Name 4 possible systemic side effects on prolonged exposure to excessive levels of glucocorticosteroids
- Hyperglycaemia
- Hypertension
- Cushing’s like syndrome
- Tanning of skin
Describe the weak anti-inflammatory action of cromolyn sodium and nedocromil sodium
- Mast cell stabilisation
- Reduce inflammatory cell recruitment
- Blunted neuronal irritant reflexes
Name 3 side effects of cromolyn sodium and nedocromil sodium
- Cough
- Throat irritation
- Paradoxical bronchospasm
What can be given to a person suffering severe exacerbation?
Bronchodilators administered by oxygen-driven nebuliser
