Lecture 19: Respiratory pharmacology Flashcards
Describe the underlying causes of asthma symptoms:
- Inflam infiltrate of bronchial wall i.e mononuclear cells, eosinophils
- Hypertrophied smooth muscle
- Oedema of the bronchial wall intersitium
- Mucous plugs
What does the inflammatory profile of the bronchial wall lead to which causes asthma symptoms?
- Inflammation
- Hyper-reactivity
- Airway obstruction
How many phases of asthma are there, and some notes on them:
Dual phase:
Immediate phase i.e allergen or non-specific stimulus activates Mast cells-> spasmogens (induces bronchospasm) and chemokines (late phase response)
Late phase: Immune cell infiltrate i.e EOSINOPHILS, TH2, monocytes etc -> All release many factors which can cause airway inflammation, airway hyper-reactivity = Bronchospasm, wheezing, coughing (side note, some factors can actually cause epi damage)
What are some classes of bronchodilators?
- Beta adrenoreceptor agonists
- Methylxanthines
- Muscunaric antagonists
- Leukotriene antagonists
What causes smooth muscle contraction in the lung?
Acetylcholine
Adenosine
Leukotriene (i.e leukotriene antagonist)
Write some notes on beta 2 agonists?
- They are agonists for the beta 2 receptors but function physiologically as an antagonist for contraction
- Activate cAMP dependant pathway which inhibits SM contraction (PKA)
i.e Salbuamol (SABA) Salmeterol (LABA)
Compare SABA and LABA:
- SABA have fast onset but short duration of action
- LABA generally slower onset but long lasting
This difference is primarily due to lipid solubility i.e structurally long side chains increase solubility
Describe in relation to the receptors where the beta agonists function:
SABA act on the EC surface of the receptor
LABA diffuse into the lipid bilayer and act on the sides of the receptor (long acting pathway)
Formoterol does a combo..
What are the potential side effects of beta agonists?
Side effects are associated with system absoprtion
- Tremor
- Tachycardia (due to lack of selectivity i.e fenoterol)
What are the methylxanthines? and how do they work?
Likely combo of effects:
- PDE inhibitor of smooth muscle and inflam cells (breaksdown cAMP which is inhibiting contraction via PKA)
- Possibly adenosine antagonist…
What are some methylxanthines?
Theophylline
Aminophylline
How do muscarinic antagonists function? and some examples
- Some inhibition of bronchoconstriction
- Inhibit mucous secretion
- No effect on inflam phase
i.e Ipratropium (SA) (POORLY absorbed), tiotropium (LA)
What do glucocorticoids target?
The immune system
What are some examples of glucocorticoids and what there effects are? and their side effects?
Budesonide, fluticasone
- Often in combo with LABA
- Side effects: Oropharyngeal candidiasis and sore throat
- Inhibits IgE production and mast cell/ eosinophil activation
How do glucocorticoids work?
- Diffuse through membrane and can act via:
- Transactivation of GR receptor = GRE, increase Anti-inflam production
- Cis-repression of GR receptor = Side effects…
- Trans-repression of GR receptor = Decrease inflammation
Describe the asthma interventions and where they target in the dual phase of asthma:
Immediate phase bronchospasm reversed by: Beta 2 agonists, Leukotriene antagonists, methylxanthines
Late phase and early phase is inhibited by glucocorticoids
Describe the order of asthma treatments:
- SABA i.e salbutamol
- inhaled corticosteroids i.e beclometasone
- LABA i.e slameterol
- Methlxanthines i.e theophylline
- Muscunaric anatagonists (LAMA)
- Leukotriene antagonist i.e montelukast
What are ICS and LABA recomended?
- To relieve when required
- Maintaince continually
But asthma treatment is a continuum and treatment follows accordingly
Where do biologics fit in to asthma treatment?
Approx 5% patients dont respond to traditional treatments so biologics are used to target specific chemokines using antibody based therapy…
Can reduce need for corticosteroids
What can biologics target in asthma?
- Allergen receptors
- Specific interleukins to prevent immune cell activation
- Antibodies
What is COPD?
- Group of related disorders
- Underlying chronic airway inflammation
- Fibrosis of small airways, obstruction/destruction of alveoli and elastin fibres in parenchyma
- Not fully reversible
What is COPD treatment?
- STOP Smoking
- Limited pharmacological treatments available
- Bronchodilators can provide some symptomatic relief, but not great
- Glucocorticoids do have small impact on quality of life, but do not slow disease progression
- OXYGEN therapy
Why are glucocorticoids not that great?
A lot of COPD is related to smoking, and smoking decreases Histone Deacylation enzymes which ultimately means there are less targets for glucocortiocoids to work and change gene transcription
How are macrolides used in COPD?
- They have antibacterial action via inhibition of protein synthesis usually but also immunomodulatory action at lower doses
- Mixed opinions
- I.e erythromycin
In essence used to decrease severity of COPD caused by the immune system
Do we want to treat coughs? What is the purpose?
- Cough: Protective response to foreign particles or mucous secretions
- Useful vs useless cough i.e we want to treat the useless one
What can be used to treat the useless coughs:
Antitussive agents
- Demulcents ile lozenges (wets back of throat in dry cough)
- Opiods i.e codiene, dextromethorphan (dirty, has side effects)
- Mucolytics (thins mucus) i.e carbocistiene
