PHARM Asthma & COPD - Week 2 Flashcards
Asthma pathology
Increased smooth muscle, build up of mucous, BM thickening.
Symptoms of asthma
- Recurring episodes of breathing problems.
- Shortness of breath.
- Wheezing/chest tightness
- Night-time or early morning coughing.
2 x types of asthma
- Extrinsic – allergic/T2 type (most common)
o Involves IgE antibodies/mast cell & basophilic degranulation
o Triggered by re-exposure to allergens (e.g., pollen, house dust mites, pets). - Intrinsic – non-allergic/non-specific (more severe)
o Hyper-responsive airways
o ‘Non-specific bronchial hyperreactivity’
o Triggered by exercise, cold, infection.
What immune cells are responsible for driving 2 types of asthma?
T2/allergic/extrinsic asthma - high eosinophils
Non-T2/non-allergic/non-specific/intrinsic asthma - high neutrophils
SABA expand. Drug type examples.
Short acting B2 agonist. Salbutamol/albuterol (ventolin/asmol).
SABA administration.
Inhalation.
What do SABAs protect against?
Exercise-induced asthma.
MOA SABAs
- MOA: mimick effect of adrenaline with selective action on B2 adrenoreceptors -> adenylcyclase -> c35AMP -> muscle relaxation/bronchodilation
SABA onset
5-15min
SABA duration of action
3-6hrs
SABA adverse effects
- Adverse effects: tachycardia, muscle tremor, receptor downreglation/desensitisation decreases efficacy in cases of overuse, infection, smoking, underlying inflammation left untreated.
LABA expand. Drug examples.
Long acting B2 adrenoreceptor agonist. Formoterol.
LABA administration.
Inhalation.
What do LABA & ICS protect against?
T2-type asthma (w eosinophilic response)
When should LABA & ICS be used?
Short term exacerbation OR for severe asthma unresponsive to other therapies.
LABA & ICS MOA
- MOA : steroids must enter cytoplasm of target cells -> acts on receptor -> translocates to nucleus -> regulating gene expression -> promote anti-inflammatory protein synthesis -> bind to pro-inflammatory transcription factors (e.g., NFkB) to downregulate inflammatory factors
LABA & ICS adverse effects
- Adverse effects: suppress endogenous glucocorticoid synthesis, Cushing’s syndrome, suppress infection & injury response, behavioural disturbances, cataracts, glaucoma, metabolic effects, growth suppression, poor delivery can cause dysphonia & oral thrush.
Omalizumab target. Recommended for which group of pts.
- Omalizumab – recombinant mAb against IgE (use restricted to severe, persistent allergic asthma uncontrolled even with high doses of corticosteroids).
Mepolizumab target. Recommended for which group of pts.
- Mepolizumab – recombinant mAb against IL-5 (use restricted to severe eosinophilic asthma in adults only).
Dupilumab target. Recommended for which group of pts.
- Dupilumab – recombinant mAb against IL-4/IL-3 receptor (use restricted to adults with severe allergic asthma).
Symptoms of COPD
- Shortness of breath
- Wheezing
- Coughing
- Increased mucous production
- Recurrent chest infections
- Muscle wasting.
Potential causes of COPD
- Smoking
- Frequent lung infections as a child
- Indoor smoke (e.g., wood, coal, cow dungs, crop residues)
- Occupational dust @ chemical exposure
- Genetic reasons (a-1 antitrypsin deficiency)
What can a1 antitrypsin deficiency lead to? How?
Early onset emphysema. Lungs lack a1 antitrypsin coating - leaving them open to damage by neutrophil elastase. Liver damage also occurs due to trapped a1 antitrypsin present here.
Signs & symptoms of chronic bronchitis.
Remember blue bloater & pink puffer.
Overweight, cyanosis, elevated Hb, peripheral oedema, wheezing, chronic daily productive cough.
Signs & symptoms of emphysema.
Remember blue bloater & pink puffer.
Older & thinner, severe dyspnoea, quiet chest, CXRT revealing hyperinflation w flattened diaphragms & permanent enlargement & destruction of airspaces distal to the terminal bronchiole.
What immune cells are responsible for driving COPD?
Neutrophils.
SAMA expand. Drug examples.
Short acting M3 antagonist. Ipatropium/tiotropium.
SAMA adverse effects.
- Adverse effects: inhibit salivation -> dry mouth, blurred vision, urinary retention.
SAMA effect.
- Protect against increased parasympathetic drive by decreasing airway muscle contraction & mucous production.
When are ICS used to treat pts w COPD?
In pts who have eosinophilic elevation.
When are short term oral steroids usually used in pts w COPD?
Recovery from COPD exacerbations.
Issues with steroid use in pts w COPD?
Suppressed immunes system -> increased risk of pneumonia.
Therapy for pts w a1-antitrypsin deficiency
Replacement therapy (derived from human plasma).
Step wise treatment for asthma. Examples of common medications prescribed.
ICS-LABA/ICS-SABA as needed, regular, low-dose ICS-LABA/ICS-SABA, medium-dose, regular ICS-LABA, add LAMA (consider high-dose, regular ICS-LABA OR anti-IgE, anti-IL5…).
LABA e.g., formoterol/symbicort.
ICS e.g., budesonide.
SABA e.g., salbutamol/ventolin.
Step wise treatment for COPD.
SABA or SAMA as needed, SABA or SAMA w LABA or LAMA, previous w ICS, LABA & LAMA & ICS recently approved, previous (consider anti-inflammatory agents).
What drug classes are typically considered relievers? Preventers?
SABA/SAMA. LABA/LAMA/ICS.
Why are SABAs preferred over SAMAs for asthma treatment?
SABAs preferred for asthma compared to SAMAs - as SABAs target all leukotrienes, histamines… whereas SAMAs only target ACh mediator.
