Respiratory Drugs Flashcards
asthma prevalance
8% of the population
Asthma cascade
irritant stimulates mast cells. Immediatly release histamine causing vasospasm. Secondary release of leukotirenes, leading to a narrowing of the bronchus due to inflammatory exudate. Tertiary is stimulus of chemotactic factors leading to cellular infliltrate which occludes the bronchioles
Why can MDI doses be smaller?
because therapy is targeted, gets into the respiratory tree. small dose causes fewer side effects
B2 agonists mechanism
agonists binds to receptor, which phosphorylates GTp and activates cAMP and PKA. PKA phosphorylates Ca channels reducing Ca influx and thus relaxing smooth muscles.
Beta 2 agonist ancilliary processes
mucolilliary clearance, decrease musculovascular permeability by then, suppress inflammatory cell mediator release.
Beta 2 pharmacokinetics
reasonable oral absorption, Metabolized by COMT/MAO 15-70% bioavailability,. t(1/2) = 6-8 hours
8-15% of dose reaches systemic circulation,
pharmacodynamics
oral_30-60 minutes, peak 1-3 hours. Inhaled: onset minutes, peak 15-30 mmin duration, 4-6h. b2 selectivity reduced at higher dose, tolerance and tachyphylaxis
beta 2 agonists effects/toxicities
tachy, palpitations, flushing, exacerbation of angina/arrthymias, vasodilation pulm artery. CNS” tremor/anxiety+headache+insomina, hypokalemia,hyperglycemia
Salmeterol: mech of action
binds to beta receptor, and then side chain dips into receptor to dual binding. this prolongs the effect, as both don’t come off at the same time. Take twice a day
Salmeterol use
does not give immediate release 30 minute onset, peak is 3 hours. give twice a day. prescribe with an inhaled steroid
MDIs
must be taken the right way. technique is important.
Ipratropium bromide
anticholinergic. about an hour to get to the peak, slower onset than beta2 agonists. 8-15% reach bronchi, 6-8 hours
Ipratropium advere effects
bitter taste, Ach effects (rare), drying of secretions does not occur.
Tiotropium
same as ipratropium, except longer half life. can get exagerated half life.
Corticosteroids
Fluticasone, Hydrocortisone, Prednisone, Methylprednisolone
Corticosteroid uses
systemic: acute severe asthma, chronic maintenance. Inhaled, prophylaxis in mild refractory asthma, combined with systemic steroids in chronic asthma.
Corticosteroids mechanism
binds to receptor, turns off of genes promoting inflammation, turns on inflammatory genes. produce effect on transcription factors. change in genes involved in inflammation
corticosteroids delivery
10% dose bronchi, 90% of oropharynx, metabolism hepatic CYP3A, low systemic concentrations
corticosteroid adverse effects
thrush, horse voice. systemic is HPA-axis suppression, bruising, cataracts, inhibit bone growth, a concern in children, behavioral disturbances, hypokalemia.
Leukotriene antagonists
Montelukast
Leukotriene
LTC4 and LTD4 are the most potent bronchoconstrictors
Montelukast-mechanism
antagonist to the CysLT1. decrease the ability to the LTDs to bind to receptors.
Motelukast-use
prophylatic and chronic maitenance, used in combination with other drugs, not as good as beta2, used for asprin induced asthma.
Montelukast-pharmdynamics
bronchodilation in 1-2 hours, duration of receptor blockade in 10-14 hours
