respiratory I + II Flashcards
(39 cards)
how do B2-agonists work?
- binds to 4th transmembrane beta agonist receptor
- GTP for GDP
- G-alpha/GTP stimulates adenylate cyclase
- stimulates cAMP
- stimulates protein kinases
- phosphorylation decreases Ca++ influx, increases Ca++ uptake, decreases actin myosin interactions and relaxes smooth muscle
what are some positive secondary effects of B2-agonists?
- enhance mucociliary clearance
- decrease microvascular permeability
- suppress mediator release from inflammatory cells
what is unique about inhaled doses?
micrograms because of effective absorption
what metabolizes B2 agonists?
COMT/MAO
inhaled bioavailability of B2 agonists?
8-15%
timing of inhaled vs oral B2 agonists
inhaled - onset within minutes, peak in 15 minutes, duration 4-6 hrs
oral - onset in 30-60 mins, peak 1-3 hrs, duration 6-8 hours
B2 agonists adverse CVS effects
- tachycardia, palpitations, flushing
- exacerbation of angina. arrhythmias
- vasodilates pulmonary artery - V/Q mismatch
B2 agonists adverse CNS effects
- tremor, anxiety
- headache
- insomnia
B2 agonists adverse metabolic effects
- hypokalemia, hyperglycemia
which is longer acting, albuterol or salmeterol and why?
salmeterol, it has a projecting arm and binds longer and stronger to the agonists binding site, so it can be given twice per day rather than 6 times for albuterol
unique potential danger of salmeterol
slight increase in sudden death vs albuterol
what are the two important anticholinergic respiratory drugs?
- ipratroprium
- tiotropium (once daily so easier for patient and therefor becoming more popular)
big differences between anticholinergic and B2 agonist respiratory drugs?
- anticholinergics have a somewhat slower onset and don’t dilate bronchioles quite to the same degree
- anticholinergics and taste very bitter and some patients can’t stand it
ipratropium bioavailability
- 8-15% gets into lungs
- less than 1% reaches systemic circulation
ipratropium duration
6-8 hours
contraindication for use of respiratory anticholinergics
renal impairment
tiotropium vs ipratropium duration?
tiotropium much longer (24 hours) vs 6-8 hours
what is the inhaled respiratory corticosteroid?
fluticasone
what are the systemic respiratory corticosteroids and order of potency?
- hydrocortisone 1.0
- prednisone 4.0
- methylprednisolone 5.0
- dexamethasone 25-30
summarize the antiflammatory mechanisms of corticosteroids
1 - inhibits enzymes producing PGs, LTs, TX, for example PLA2 and COX2
2 - inhibits gene transcription of inflammatory cytokines, IL-1, 3, 4, 5, 6, TNFa, GM-CSF
3 - induces enzymes that degrade bradykinin and tachykinin
4 - increase B2 agonist receptor transcription
5 - reduces histamine producing cell trafficking into airways
inhaled corticosteroids bioavailability
about 10%, the other 90% is swallowed.
inhaled corticosteroids metabolism
liver CYP3A
local adverse effects of inhaled corticosteroids
- thrush - C. albicans (gargle with water)
- hoarse voice
systemic adverse effects of inhaled corticosteroids (at very high doses)
- suppression of adrenal axis
- bruising
- cataracts
- inhibit bone growth in children
- behavioral disturbances
