Resp Pharmacology Flashcards
What are the two main groups of management for asthma?
Relievers - rapid reversal to prevent bronchoconstriction eg. b2 antagonist
Controller - on-going suppression of airway inflammation eg. inhaled corticosteroids
What do relievers do and what are the two main groups, examples?
Decrease smooth muscle contraction by reversing effects of leukotrienes, histamine (mast cells), acetylcholine (cholinergenic n.) endothelin-1 (epithelium) to relieve
1. SABA - binds b2 on sm inducing relaxation but no not inhibit inflammation. eg. salbutamol and terbutaline
2. LABA - additional lipophilic tail that binds to a second binding site of b2-AR eg. salmeterol (delayed onset) and formoterol (rapid onset so reliever), ipratropium bromide (muscarinic cholinoceptor antagonist so only reduced Ach induced constriction), montelukast (leukotriene receptor antagonist)
What are controllers for asthma and examples?
Suppress airway inflammation and provide better long term control with many add on therapies with inhaled corticosteroids eg.(musc antagonist, salmeterol, leukotriene antagonist, anti-IgE, anti-IL5) They dont relieve bronchoconstriction but are first line therapy for Th2 driven eosinophilic asthma
EG. FLUTICASONE
What are the clinical benefits of controllers?
-decrease inflammation, sputum eosinophils and NO
-less airway narrowing
-improved lung function (increased FEV1)
-reduce asthma medication use
-fewer exacerbations and hospitilizations
What are 5 difficulties treating asthma?
- irregular use of inhaled medication (non-adherence)
- incorrect technique
- inadequate treatment of comorbidities
- asthma heterogenicity - some respond worse to ICS
- true glucocorticoid resistance
Advantages (3) of combined inhalers and give an example?
- improved adherence as only have to use one
- reduced over-reliance on SABA only bronchodilators
- reduced frequency of asthma attacks
eg. budesonide and formoterol = symbicort
How does leukotrienes mediate inflammation and how are they controlled?
Leukotrienes produced by mast cells and eosinophils bind CysLT receptor and induce airway narrowing by promoting
1. secretion of mucus
2. contraction of sm
3. leakage of bv
4. influx of eosinophils
LT receptor antagonists block cysLT which inhibits LT induced sm contraction and inflammation but not useful as a reliever
eg. montelukast
Name an add on controller that targets free IgE preventing binding?
Omalizumab is used to treat uncontrolled severe allergic asthma which improves symptoms and decreases usage of ICS and b2-AR agonists
Two examples of omalizumabs?
- mepolizumab - targets free IL5 (activates eopinophils)
- benralizumab - targets IL5-R on eosinophils
IL5 is key cytokine in proliferation, activation and survival of eosinophils
Causes of hypoxaemia?
- low inspired O2 - asphyxiation
- Hypoventilation - retained O2
- Diffusion limitation - gas transfer problem
- Right-Left shunt - heart problems
- V/Q mismatch - lung/heart problems eg. dead space with PE
2 consequences of hypoxaemia?
- failure of oxidative energy metabolism leading to cell death
- anaerobic energy metabolism compensation causing increased glycolysis with lactate build up so lowered pH
What role does chronic hypercapnia play in O2 therapy?
Chronic hypercapnia (over 50mmHg) desensitizes chemoreceptors to CO2 losing sensitivity so only O2 drives respiration so if patient receiving O2, then CO2 is building up as respiration not driven by low O2 (as receiving therapy for it) and CO2 narcosis occurs as resp. centers because unreactive lowering consciousness.
What are the normal O2 saturation levels?
Normocapnic - acute asthma, pulmonary oedema 94-96
Hypercapnic - COPD with high risk O2 insensitivity 88-92
What does COPDX mean?
C- case finding
O - optimize function
P - prevent further deterioration
D - develop care plan
X - manage exacerbations
Diagnosis system for COPD
What are the numerical levels of FEV1/FVC and FEV1 that indicate airflow limitation?
FEV1/FVC less than 0.7 and FEV1 less than 80% after bronchodilator given indicate fixed airflow limitation (asthmatics will have normal levels after reliever but COPD will not)
