Pharmacology of the Treatment of Airway Diseases Flashcards
FEV green yellow and red
Green over 80
Yellow 50-79
Red under 50
Asthma patho
INflammation, edema, mucous secretion, thickened airway wall, obstruction
Bronchial hyperresponsiveness
IL5 is an important cytokine that activates eosinophils and neutrophils…they can migrate into the airways
Tx of asthma severity
Step 1 - intermittent tx
Persistent ashtma is anything above that
Topical application
Aersol delivery
Few side effects
Most pts can use
Spacer limits particle size
Slow deep breath for 5-10 seconds
MDI
Nebulizers
Dry powders
Cheap, portable and fast
No coordiination…good for young children or elderly…uses pressurized gas and takes 15 minutes
Latose or glucose powders…need high flow and powder irritating…not good for young children or elderly and temp and humidity probs
Relivers
Controllers
Quick relierf (bronchodilators)..B2-agonists (short acting) and anti-cholinergics
Controllers - inhibit late phase inflammatory response (all other and long acting B2-agonists)
B2-adrenergic agonist MOA
Stimule the B-adrenergic receptors on airway smooth muscle
Decrease airway resistance by increasing formation of cAMP…this increase protein kinase A and then smooth muscle relaxation
Onset of action SABA
Most effective, MDI or nebulizer
Albuterol
Drug of choice for acute asthma…works in 1-5 minutes for 2-6 hours
Used for step 1 (need less than 3X week) and acute exacerbations of ALL steps
Oral B2 adrenergics
Salbutamol
Works in 1-2 hours and durations is 4-8 hours
Young children under 5
Occassional wheezing from upper resp infections
More advers eeffects
Slow release and short acting..less efficacious
LABA B2 adrnergic agonists
INhaled and long acting
Salmeterol
Takes longer to act (NOT for acute)
Longer durations
Long side chain inserts into lipid bilayer and PM gradullary diffuses
Long duration masks worsening of inflammation..not good for monotherapy
NEVER use on own and use with corticosteroids (step 3-6)
Epinerphine
Ultra-short acting
Life therating
Unconscious or severe resp distress
Not the drug of choice
B2 adverse effects
Uncommon in inhaled
Cardiac - tachy, palps, arrythmias
CNS - nervousness, restless, anxiety
Skeletal , muscle tremors
Dangers of B2 agonist overutilization
INcrease hyper-responsiveness
Death from worsening dz
Inhaleer more than 3X a week…need anti-inflammatory therapy
Monitor dz
Death - use long-acting B2-inhaler for actue attack
Anticholinergic agents
Comp inhibit M3 receptors
Block contraction of airway smooth muscle
Lower and less nitense than B2 agonists
Ipratropium and tiotropium with SEs
Ip - inhaler or nebulizer…works for 6 hours
Tio - dry power, works for 24 hours…add on for Step 4 (over 12 y/o)
Can be combined with B2 agonists…albuterol and ipratropium
Little sys absorption…dry mouth, blurred visoion, urinary retention…glaucomoa in the elderly
CSs
First line ofr step 2-4
Fluticasone - inhaled
Prednison - oral
Prophylactic…6-12 hours to work
Prevent exacerbation recurrence
Dose-dependnet
Max improvement - several weeks
Do NOT relax airway smooth muscle directly
Inhibit the inflammation and reduce reactivity…restores sensitivity to B2 agonists
Local and systemic adverse effects of CSs
Local (inhaled) - voice weakness, thrush, suppress hypothalamus, growth suppression, osteoporosis and cataracts
Systemic - fluid retention, weight gain, osteo, cataracts, diabetes, HYPA suppression…make sure to taper
Advair
Long acting B-agonist with low/medium dose of ICS
Pts not adequately controlled by steroids alone (steps 3-6)
Advair - combination of almetrol and fluticasone
Anti-IgE - omalizumab
Recom humanized monoclonal AB against IgE
MOA- IgE binds FCeRI receptor on mast cells
Allergen binds cell-bound IgE
Crosslinks receptor…histamine release
OMalizumab binds the free IgE
PK and effects of Anti-IgE
Single sq injection every 2-4 weeks
Use in pts with severe asthma not controlled by std drugs (long acting B agonist and corticosteroid)
OR pts iwth IgE mediated sensitivity (skin prick test)
INjection site rxn…slight increast risk of circulatory effects…maybe allergic rxns?
Mepolizumab
Pts with severe esosinophilic asthma
IV or SC
Neutrlizes IL-5
Leukotrienes
Secreted by mast cells and eosinophils
Binds cys-LT1 receptor on smooth muscles
Potent bronchoconstrictors
Montelukast
Oral leukotriene receptor antagonist
Competitive nihiborrs of cyc-LT1 receptor
Prophylactic
Some don’t respond
Less efficious than mod-high
Second line for Step 2
Use in combo iwth B2 agonists and steroids (step 3 and 4)
**8Better adherence
PKs, adverse effects with singulair
Oral, 1X daily
Abnormal liver function tests
Suicide?? Mood changes/??
Thophylline
Bronchodilator and antiflam
Activates histone deacetylases and decrease transcription of proinflam genes
Phopshodiesterase inhibitor…prevents conversion of cAMP to other things
Allows cAMP to promote bronchodilation
Theophylline PKs, adverse effects and uses
Oral or IV
T1/2 increased - heart failure, PE, AB interations
Fatal intox if administered IV too fast…seizures often precede toxicity
Second line to low dose ICS (step 2)
Add-on (in addtion to ICS..step 3 and4)
Pts who can’t take ICS, aren’t adherent or don’t have insurance
Low dosage making a comeback
Rofumilast
COPD - FDA approved
Trialse for allegens
PDE4 inhibitor which increases cAMP
Bronchodilator
Anti-inflam response (reduces esosinophil mirgrations)
More selective to aitrway than theophylinne
Adverse - weight loos, insomnia, mood
Azithromycin
Severe asthma - high risk for exacerbations and infection
Non-esosinphilic - neutrophilic resistant to CSs
Anti-bac and anti-infolam
Frwquency of severe exacerbations is primary endpoint
tx of COPD
Rofumilast
Salmetrol (long acting)
Long acting anti-cholinergic (tio)…if reversible
CSs - some respond to short course
Theo - effective for some…add to B2
Daily azih - prevent exacerbations
Bronchodilator effects of drugs
Beta agonists increase AC…increase AMP…increases dialtion
Theophylline and rofumilast…inhibit PDE and decrease AMP
Theophylline and muscarinic antagonists both block bronchocontstriction
