Pathophysiology + Pharmacology of Asthma Flashcards
What is asthma?
Recurrent + reversible (in short term) obstruction to airways in response to stimuli
What are the causes of asthma attack?
Allergens
Exercise
Respiratory infections
Smoke, dust, environmental pollutants
Describe structure of smooth muscle in airways in acute asthma
Contraction of smooth muscle
Mucus hypersecretion
Air inflammation
What are the symptoms of acute asthma?
Dyspnoea
Wheezing
Coughing
What is dyspnoea?
Loss of breath
What hypersensitivity reaction is sensitisation of asthma?
Type I
Describe what happens in sensitisation to asthma
IL-4 stimulates production of IgE by B cells + activate mast cells
IL-13 stimulate mucus secretion from bronchial submucosal glands
+ stimulate IgE by B cells + activate mast cells
IL-5 activates locally recruited eosinophils
What is basic immediate response?
Bronchospasm
What is basic delayed response?
Inflammatory reaction
Describe immediate phase
Bronchoconstriction
Increased mucus production
Vasodilation
Release of mediators
Describe delayed phase
Recruitment of leukocytes + T cells by cytokines, produced by mast cells
Release of mediators of inflammation
Describe the immediate response on re-exposure to antigen
Antigen binds to IgE-IgE receptor complex
Cross links IgE receptors
Stimulates Ca2+ entry into mast cells evoking …
Release of histamine + leukotrienes = smooth muscle contraction
Release of eosinophils that attract cells causing inflammation
What are the effects of mast cell mediators?
Bronchospasm
Increased vasodilation
Mucus production
Recruit mediator-releasing cells
What are examples of mast cell mediators?
Histamine + leukotrienes
Describe what happens in late phase
More pro-inflammatory mediators released =
Eosinophil major basic protein = epithelial damage + airway constriction
Cytokines = contribute to amplification of inflammation
Describe chronic asthma
Increased smooth muscle
Accumulation of interstitial fluid
Increased mucus
Exposed sensory nerve endings
How do you diagnose?
Demonstrate increased airflow obstruction (spirometry)
Wheezing
Eosinophil count in blood test
Allergy tests
What does parasympathetic intervention do?
Worsen symptoms of asthma
Describe what happens in parasympathetic intervention
IP3 increases = Ca2+ increases
= bronchoconstriction + increased mucus
What does sympathetic innervation?
Improve symptoms
Describe what happens in sympathetic intervention
Adrenaline acts on beta-2 receptors = bronchodilation
What does chromolyn do?
Prevents mast cells from exploding
What treatments are used for immediate phase (bronchospasm)?
Bronchodilators
- Beta-2 agonists
- Muscarinic antagonists
- Xanthines
Describe what beta-2 agonists do in immediate phase
Direct action on beta-2 receptors on smooth muscle
= smooth muscle relaxation
Decrease mucus
How are beta-2 agonists given?
Inhalation
What are the 2 types of beta-2 agonists (inhaler)?
Short acting = salbutamol
Long acting = salmeterol
What are the side effects of beta-2 agonists?
Tolerance
Tremor
Describe the action of salbutamol on beta-2 receptors
Stimulation receptors
= activation of adenalyl cyclase
+ increase cAMP + PKA activation
= smooth muscle relaxation
Describe what muscarinic antagonists do in immediate phase
Dilate bronchi
Decrease mucus
Describe how muscarinic antagonist dilate bronchi
Block Gq signalling pathway
= increased Ca2+ conc
What is an example of muscarinic antagonists?
Ipratropium
Describe how ipratropium is used
Inhalation
Why can ipratropium not cause many side effects?
NOT well absorbed so doesn’t get into circulation
What do xanthines do in immediate response?
Bronchodilation
Anti-inflammatory properties
Describe how xanthines cause bronchodilation
Block phosphodiesterase
= increase cAMP = bronchodilation
What is an example of xanthine?
Theophylline
What is the problem with theophylline?
Narrow therapeutic window
What are the side effects of theophylline?
HR change
Arrhythmias
CNS stimulation
GI disturbances
What treatments are involved in the inflammatory phase?
Glucocorticoids
Describe what glucocorticoids do in the inflammatory response
Inhibit transcription of phospholipase A2
= decrease production of inflammatory mediators
What are examples of glucocorticoids?
Beclomethasone = inhalation
Prednisolone = orally (short term)
Hydrocortisone = injection
What are examples of glucocorticoids?
Oral candidiasis
Cushing like syndrome
What does sodium cromolyn do?
Prevents the release of histamine + inflammatory mediators
What do cysteinyl-leukotriene receptor antagonists do?
Block leukotrienes induced bronchospasm
What are cysteinyl-leukotriene receptor antagonists effective for?
Mild persistent asthma
What is an example of cysteinyl-leukotriene receptor antagonists?
Montelukast
Why can’t propanolol be used to treat hypertension with patients with asthma?
Because beta 1 + 2 blockers = beta-2 blocked = bronchospasm
Why can ACE inhibitor captopril not be used in patients with asthma?
Induce cough
Why can NSAIDs precipitate asthma?
= in aspirin = COX1/2 blocked = increase leukotriene generation
