Asthma Drugs Flashcards
Aims of asthma treatment
Decrease inflammation
Prevent bronchoconstruction
Restore airway calibre to normal
Atopic and non-atopic triggers
Non atopic: exercise; resporatory infection, pollutants (intrinsic)
Atopic: pollen, dust, animal fur (allergic) - trigger B cell production = inflamm, bronchoconstriction
Phases of asthma attack
Immediate/early- = bronchodilator - bronchospasm, mast cells release spasmogens - histamine, prostaglandins - mast cells release inflammatory mediators - interleukins, macrophage inflam protein, tumor necrosis factor, chemotaxins and chemokines attract WBC Late phase - - anti-inflammatory - progressing inflam reaction - lymphocytes and eosinophils invade - release cytokines, chemokines - hyperplasia
Beta-2 adrenergic receptor antagonists
- bronchodilator
direct action on B2 adreno-receptors on bronchiole smooth muscle causing them to relax and dilate
inhibit mediator release from mast cells
act on cilia to increase mucus clearance
short acting = Salbutamol, Terbutaline, last 4-6 hours, use when needed
longer acting = Salmeterol, last 12 hours
given by inhalation to minimize tremor
tolerance can develop, overcome by glucocorticoids
Theophylline
- bronchodilator
Eg. Xanthine
- PDE inhibitor
- used with steroids when asthma response to B2 agonist inadequate
- can be given i.v in acute severe asthma
SE = stimulant: tremor, sleep disturbance, stimulate heart, vasodilation, anorexia, nausea and vomiting
Muscarinic receptor antagonists
- bronchodilator
Eg. Ipratropium
- max affects 30 mins, last 3-5 hours
- poorly absorbed in systemic circulation
- inhibits elevated mucus secretion and increase clearance of secretions
- blocks action of endogenous acetylcholine at muscarinic receptors
Leukotriene receptor antagonists
- bronchodilator
Eg. Monteleukast (x 1 daily), Zafirlukast (x 2 daily)
- given orally
- prevents exercise-induced and aspirin-sensitive asthma
- action additive with B2 agonists
- main use is add on for uncontrolled mild/moderate asthma
- act at cysteinyl-leukotriene receptors
on bronchiole smooth muscle cells
- prevent actions of leukotrienes which are:
> bronchial spasmogens
> stimulate mucus secretion
SE= headache, GI effects
Glucocorticoids
- anti-inflammatory
Eg. Beclometasone diproprionate, Budesonide, Fluticasone propionate, Prednislone/Hydrocortisone
- given by inhalation
- full effects may take days to develop
- decrease production of cytokines, spasmogens, leukocyte chemotaxins to decrease bronchospasm = decrease inflammatory cells
Mechanism of action of glucocorticoids
- enter cells and binds to receptors in cytoplasm
- receptor complex moves to nucleus
- binds to DNA in nucleus
- alters gene transcription - repression of interleukin 3
Clinical use of glucocorticoids
to help control attacks
give inhaled steroid with additional agent for severe asthma eg Budesonide + B2 agonist
iv hydrocortisone and oral prednisolone for acute exacerbation
short course oral prednisolone for deterioration’s
SE = oropharyngeal thursh, dysphoria (difficulty speaking) - minimised by use of spacer
oral/regular large doses = adrenal suppression
Cromoglicate
Eg. Nedocromil Sodium
- can decrease both early and late phase responses
- decreases bronchial hyper-reactivity
- effective in asthma caused by antigen, exercise, irritants
- unpredictable response - children respond better
mechanisms:
decrease neuronal reflexes
inhibit release of T cell cytokines
affects inflammatory cells and mediators
SE = irritation of upper respiratory tract, hypersensitivity reactions
inhalation
Biological agents
Eg Omalizumab
- recombinant DNA-derived humanized IgG1 monoclonal antibody
- subcutaneous injection every 2-3 weeks = absorbed slowly
mechanisms:
binds to human IhE
inhibits binding of IgE to IgE receptor on surface of mast cells and basophils
inhibits IgE mediated cascade of asthma causing inflammation and bronchoconstriction
SE = anaphylaxis, malignancies
