ELM 16: Asthma 1 Flashcards
What is Chronic Obstructive Pulmonary Disease?
- Chronic
- Narrowing of airways
- Inflammatory
- Combination of chronic bronchitis and emphysema
- Poorly reversible
What is chronic bronchitis?
Persistent cough with mucus production
What is emphysema?
Destruction of tissues around alveoli
What is Bronchial asthma?
- Chronic
- Narrowing of airways
- Inflammatory
- Reversible
What are the 2 overall main causes of asthma?
Genetic factors, eg allergy genes
Environmental influences in early life
What are some specific triggers of asthma?
Excreta of dust house mites
Pollen
Cold air
Exercise
Animal fur or saliva
Fungal spores
Drugs
Environmental pollutants
What are some characteristics of an asthmatic airway?
- Mucus plugging
- Goblet cell metaplasia
- Epithelial desquamation
- Thickening of basement membrane
- Oedema
- Smooth muscle hypertrophy and hyperplasia
- Infiltration by eosinophils and neutrophils
- Submucosal gland hypertrophy and hyperplasia
How do allergies induce asthma?
- Inhale allergens that trigger allergic immune responses
- Dendritic cells sample the allergen and display pieces of allergen on surface
- Dendritic cells migrate to lymph node and activate T cells and induce clonal expansion and TH2 polarisation
- TH2 cells produce inflammatory cytokines that induce allergic inflammation and asthmatic responses
Why can asthma attacks be considered biphasic?
Split into two phases
Early phase = Bronchospasm
Late phase = Inflammation
What are mast cells and what is their role as part of the immune system in allergic asthma?
Key in early phase
- Have IgE antibodies on surface that become cross linked by an antigen
- Mast cell triggered to degranulate and release preformed mediators
What are some preformed mediators released by mast cells?
Histamines
Leukotrienes
Prostaglandins
Thomboxanes
Prostacyclins
What are some early mediators of bronchial asthma?
Acetylcholine and Leukotrienes C4 D4 E4
- Contraction of airways smooth muscle
- Increased vascular permeability
- Increased bronchial secretions
What are some later mediators of bronchial asthma?
Leukotrienes C4 D4 E4, Interleukins, Growth factors
- Contraction of airways smooth muscle
- Increased vascular permeability
- Increased bronchial secretions
- Remodelling
What is the NICE treatment pathway for asthma?
Treatments are given one by one and another is added if previous is ineffective on its own
- Short acting beta agonist (SABA) inhaler
- Low dose inhaled corticosteroid
- Leukotriene receptor antagonist
- Long acting beta agonist
- Maintenance and reliever therapy
- Increase steroid dose
- Additional drug
What are the two classes of anti-asthma drugs?
Bronchodilators
Anti-inflammatory drugs
What class of anti-asthma drug is beta adrenoceptor agonists?
Bronchodilators
What is the mechanism of Beta2 adrenoceptor signalling?
- Agonist binds and triggers GPCR pathway
- Stimulate adenylyl cyclase to increase cAMP and activate PKA
- Myosin light chain negatively modulated and calcium levels fall
- Relaxation of smooth muscle in airway
- Activation of B2 receptors in mast cells also prevent them from degranulating
What are some side effects of Beta agonist bronchodilators?
Tremor
Tachycardia and palpitations
Nervous tension
Hypokalaemia
Headaches
Muscle cramps
What is a SABA drug?
Short acting beta agonist
4-6 hours
EG Salbutamol and Terbutaline
What is a LABA drug?
Long acting beta agonist
12 hour
EG salmeterol and formoterol
How does salmeterol remain in the tissues for a long time?
Its lipophilic so dissolves in the membrane and leaks out slowly
How are SABA drugs administered?
Inhaled but available as tablets, oral solution, injectable solution
What is an MDI as a route of treatment administration?
Metered Dose Inhalers
- Pressured cannisters of drug in a device with a mouthpiece
What are some positives and negatives of metered dose inhalers?
- Reduces amount entering systemic circulation
- Reduces side effects
- But difficult to coordinate inhalation so only 10% enters lungs
What is a spacer divider?
Medicine from MDI is dispensed into spacer divider before inhaling
Improves drug delivery
What are nebulisers?
Uses compressed air or ultrasound to atomise medication into patients air stream
Medication loaded into device in liquid form
