airway therapeutics Flashcards
Describe the inflammatory cascade in asthma (and how it is prevented at each stage).
1 - inherited or acquired factors - genetic predisposition, viral, allergen or chemical (avoidance of precipitate)
2 - eosinophilic inflammation (anti-inflammatory medication - corticosteroids, cromones, theophylline)
3 - mediators, Th2 cytokines (antileukotrines or antihistamines, monoclonal antibodies)
4 - twitchy smooth muscle (bronchodilators - B2 antagonists and muscarinic antagonists)
Describe the use of corticosteroids in asthma and COPD.
- may cause pneumonia in COPD due to local immune suppression and impaired mucocillary clearance
- oral steroids (prednisolone) have low therapeutic value, only used for acute exacerbations not maintenance
- inhaled steroids (beclomethasone) have a high therapeutic ratio, used for maintenance and monotherapy in asthma
- used as ICS/LAMA/LABA combo in COPD not monotherapy
- reduces exacerbations in eosinophilic COPD
why is a spacer a good idea?
- avoids coordination problems with pMDI
- reduces oropharyngeal and laryngeal side effects
- reduces systematic absorption from swallowed fraction
- acts as a holding chamber for aerosol
- reduces particle size and velocity
- improves lung deposition
when are cromones used?
- only in asthma
- mast cell stabiliser
- effective in atopic children
- inhaled route only
- not used much due to poor efficacy
how are cysteinyl leukotrienes generated?
- by inflammatory cells such as mast cells and eosinophils (e.g LTD4)
- they have been correlated with increased vascular permeability, oedema formation, increased mucus and decreased mucocilliary transport as well as recruitment of inflammatory cells.
Describe leukotriene receptor antagonists.
- only used in asthma
- montelukast (oral)
- less potent anti-inflammatory than inhaled steroid
- used as an additive to inhaled steroid
- effective in atopic asthma
- also in allergic rhinitis
Describe anti-inflammatory, anti-IgE drugs.
- omalizumab
- inhibits the binding to the high affinity IgE receptor > inhibits TH2 response and associated mediator release
- injection every 2-4 weeks for asthma only
- for severe asthma
- very expensive
- little effect on pulmonary function but reduces exacerbations
Describe anti-inflammatory anti-IL5 drugs
- mepolizumab, benralizumab
- blocks the effect of the TH2 cytokine IL-5 which is responsible for eosinophilic inflammation in asthma
- injection every 4-8 weeks - only for asthma
- severe eosinophilic asthma
- very expensive
- reduces exacerbations but little effect on pulmonary function or symptoms
Describe anti-inflammatory, ant-IL4 drugs.
- dupilumab
- blocks effect of TH2 cytokines IL-4 and 13 which are responsible for eosinophilic inflammation, IgE, airway hyper-relatability and mucin production
- injection every 2 weeks
- severe refractory asthma
- very expensibe
- good effect on pulmonary function also reduces exacerbations and oral steroid sparing effect
- effective in atopic dermatitis and nasal polyposis
Describe bronchodilators.
- stimulate bronchial smooth muscle B2 receptors, increase cAMP
- SABA - salbutamol, LABA - salmeterol/fomoterol
- combination inhalers
- used in asthma (usually ICS/LABA dual) a d COPD (LAMA/LABA dual or ICS/LABA/LAMA triple)
- high therapeutic ration when inhaled
- systemic B2 effects if given systemically or at high inhaled doses
- high nebulised doses given in acute attack
what do the muscarinic (cholinergic) receptors do?
M1- receptors enhance the cholinergic reflex
- M2 - receptors inhibit acytlcholine release
- M3- receptors mediate bronchoconstriction and mucus secretion
Describe muscarinic antagonists.
- block post junctional end of M3 receptors
- short-acting =ipratropium
- Long acting = tiotropium
- inhaled route only high therapeutic value
- used mostly in COPD to reduce exacerbations, on its own or as a dual or triple
- also used in asthma as triple therapy as add on to ICS/LABA
- high nebulised doses of ipratroprium used in acute COPD and asthma
Describe methyl-xanthines.
- oral (theophylline) for maintenance therapy
- useful for nocturnal drips
- used as in haled steroids as complimentary non steroidal ant-inflammatory
- IV (aminophylline) for acute attacks
- non selective phosphodiesterase inhibitor
- adenosine antagonist
- low therapeutic ratio
- used in asthma and COPD
what is Roflumilast?
- COPD only
- oral tablet
- minimal effect on FEV1 - anti-inflammatory action
- reduces exacerbation (additive to LABA or LAMA)
- adverse effects ; nausea, diarrhoea, headache, weight loss.
- rarely used
what do mucolytics do?
- oral carbocistiene, erdosteine
- to reduce sputum viscosity and aide sputum expectoration in COPD
- rarely used
- only as add on
