RESP - E. RESP PHARMACOLOGY 2-COVERED Flashcards
anti-inflammatory agents
- preventative: don’t reverse an attack
- target late phase of asthma response
- take daily
- low does of an ICS
aka
glucocorticosteroids
glucocorticoids
steroids
different forms of steroids
- act at intracellular glucocorticoid receptor
INHALED: (fewer systemic side effects, can give low dose)
- beclometasone
- budesonide
- ciclesonide
- fluticasone
ORAL: (for acute attack, for sys conditions where can’t deliver directly to tissue where inflam is, can take hours)
- prednisolone
IV: (life-threatening asthma)
- hydrocortisone (water-soluble)
Glucocorticoid receptor
- activation of genes (all anti-inflam genes)
Annexin A1
B2-ARs
anti-inflam cytokines: IL-10, IL-12 - repression of genes (pro-inflam mediators)
Infam cytokines: IL-2, TNF-alpha
chemokines
inflam enzymes: COX-2
Annexin A1
- upregulation of anti-inflam genes (eg - annexin a1)
- annexin A1 acts through formyl peptide receptors
inhibits release of histamine from mast cells
inhibits cPLA2-PGs (cytosol phospholipase A2)
B2-AR expression
- steroids increase transcription of B2-AR
- protect against downregulation of B2-AR after long-term use
- benefits of steroidal co-administration with B2-AR agonist
side effects of corticosteroids (all due to dampening down immune response)
- throat infections/oral candidiasis with inhaled
- osteoporosis (bone demineralisation, loss calcium from bones so increase calcium intake - bisphosphonates)
- adrenal suppression in children (leads to reduction in growth rate)
use lowest effective dose of steroid and don’t exceed max
monitor height - indigestion (interfering with release of prostaglandins)
- chicken pox
- withdrawal effects so reduce steroids gradually if >3 weeks
steroid resistance
- severe asthma/COPD - poor response to steroids
- genetic resistance so same genes aren’t changed by GC receptor
- GR modification
- decreased nuclear translocation of GR to nucleus
- increased efflux of steroids
Leukotrienes role in inflammation and asthma
- stimulate mucus secretion
- bronchoconstriction
- role in airway remodelling
- hyper responsiveness
- link with exercise-induced asthma
cysteinylLeukotriene receptor antagonists (Montelukast, Zafirlukast)
- oral
- block LT receptors so block inflam actions of cystLTs
- bronchoconstriction blocked
- LT synthesis inhibitors eg - Zileuton
side effects of cysteinylLeukotriene receptor antagonists
- headache, rash
- nausea, jaundice, liver toxicity
- mood disorders/suicidal thoughts reported with montelukast
Omalizumab (Xolair)
- severe, allergic asthma that can’t be controlled by steroids
- monoclonal antibody against free IgE
- prevents IgE binding to immune cells and hence prevents allergen-induced mediator release
- sc injection every 2-4 weeks
bronchoconstriction as adverse drug reaction
- NSAIDs inhibit COX so more AA LT production which sets off asthma response
- B-AR antagonists
non-selective (propanolol) will counteract any bronchodilation and will produce more constriction
‘selective’ (atenolol) - contraindicated in asthma/COPD - drug allergy
penicillins, cephlasporins, tramadol, dipyridamole
Cromones (sodium cromoglicate)
- preventative (early + late)
- benefit in exercise-induced asthma
- inhalation
- mast cell stabiliser? and hence mediators aren’t released
Mucolytics (Carbocysteine, Mecysteine)
- antioxidants
- break up thick mucus
- COPD
Cough
- protective mechanism
- triggered by irritants
- cough reflex caused by sensory nerves in upper airways telling brain to stimulate cough
- diaphragm, abdominal muscles, intercostal muscles involved
- inflammation - hyperactivity of sensory nerve (COPD and asthma)
