It Ain't Easy being wheezy: Respiratory Drugs 2: corticosteroids in Asthma Flashcards
Corticosteroids - mechanism of action
how do coritcosteriods work?
diffuse into cytoplasm then bind to receptor then move to nucleus to modify transcription
Corticosteroids - mechanism of action
what can corticosteroids increase and decrease?
think inflammation
Increase anti-inflammatory mediators
Decrease pro-inflammatory mediators
Corticosteroids - mechanism of action
what do Glucocorticoids inhibit?
think interleukins and immune cells
inhibits:
- IL-4
- IL-5
- IL-13
from activating eosinophils and B cells
Corticosteroids - mechanism of action
what does is Omalizumab and what does it do?
it is an anti-IgE antibody that can stop IgE antibodies from stimulating Eosinophils and Mast cells
Corticosteroids - mechanism of action
what 3 things can activate mast cell degranulation (and thus start asthma)?
think elements and condition of air
- SO2
- Ozone
- airway dehydration
Corticosteroids adverse reactions
what are 6 adverse reactions of corticosteroids if reactions are systemic and in prolonged high doses?
think effects on adrenals, bones, metabolism, infection, gastrointestinal tract and blood pressure
- adrenal suppression
- osteoporosis
- cushing’s syndrome (metabolic effects)
- suppression of infection response
- Gastrointestinal AKA stomach upset
- hypertension
Corticosteroids adverse reactions
what are adverse reactions of corticosteriods when they are taken with an inhaler without a spacer device?
think oropharyngeal region, throat and voice
- oropharyngeal candidiases (thrush)
- sore throat
- croaky voice
Minimising adverse drug reactions for corticosteroids
why do inhaled corticosteriods have reduced adverse effects even though 80-90% is swallowed into the GI tract and only 10-20% is inhaled into the lungs?
think liver
corticosteriods that are inhaled are designed so that they are inactivated by the liver via first pass metabolism
Asthma
what is asthma
think phases, allergies and what physiological changes occur in asthma
inflammatory condition that consists of 2 phases, immediate and late.
it can be allergic or non-allergic
There is:
- inflammation of airways
- bronchial hyper-reactivity
- reversible airway obstruction
Asthma
Outline the immediate phase of asthma
think stimuli, mast cells and production of molecules
Eliciting agent (allergen or non-specific stimulus) stimulates mast cells leading to 2 outcomes:
- production of different mediators like spasmogens, promoting bronchospasm
- production of chemotaxins, which initiate the late phase
Asthma
outline what happens in the late phase of asthma
think chemotaxins, release of molecules, what the release of these molecules cause and what symptoms will be present as a result
- chemotaxins cause infiltration of Th2 cells [cytokine-releasing], monocytes and Eosinophils.
- this causes 2 outcomes:
- release of EMBP and ECP from eosinophils
- other mediators (eg CysLTs and neuropeptides)
3a. release fo EMBP and ECP from Eosinophils causes epithelial damage, leading to airway hyperactivity
3b. other mediators also cause airway hyperactivity and airway inflammation
- both physiological changes cause further bronchospasms, wheezing and coughing
Asthma
what can immediate phase bronchospasms be reversed by?
think agonists, antagonists and a drug beginning with T
- B2 adrenoceptors agonists
- cysLT-receptor antagonists
- theophylline
Asthma
what can chemotaxins and late phase asthma be inhibited by?
glucocorticoids
Asthma treatment
describe the 1st, 2nd and 3rd choice drugs for Asthma
think agonists, different administrations of corticosteriods and antagonists
1st: B2 adrenergic agonists (eg salbutamol and salmeterol)
2nd: inhaled corticosteroids
3rd: Cys-leukotriene receptor antagonist (montelukast)
salbutamol = fast relief
salmeterol/formoterol = long action duration and also prevention
Cys-leukotriene = cys-LT
COPD
what is COPD
small airways fibrosis due to smoking or occupation
