Flashcards in Pharmacotherapy of Asthma and COPD Deck (85)
SNS innervates what in the lung?
primarily blood vessels releasing Nor which causes vasoconstriction via a-1 and a-2 receptors (blood vessels also have B2 receptors but Nor has very little affinity for them). B2 can be activated with Epi but there is very little
there isn't much PNS to vessels
PNS (cholinergic) innervates what in the lung?
bronchial smooth muscle (no SNS)
Where are Muscarinic receptors highest in the lung?
trachea and large bronchi
Where are adrenergic (B2) receptors highest in the lung?
What do pre-synaptic M2 receptors do?
attenuate PNS constriction
What happens to M2 receptors in asthma/COPD?
eosinophils release basic proteins (cationic) that damage M2 receptors so increased Ach is released
What does nicotine from smoking do?
stimulates PNS and acts on nerve terminals (pre and post) and helps releases Ach (can release other neurotransmitters as well)
What other things can make Ach?
inflammatory cells like macrophages, T cells, and epithelial cells
M3 receptors are linked to what GCPR?
M2 receptors are linked to what GCPR?
Gi (reduced levels of cAMP)- particularly when B2 agonists are given
What else does M3 stimulation cause?
remodeling of bronchial smooth muscle via a-actin deposition on ECM
How is M3 stimulation on vessel different from bronchial smooth muscle?
stimulation (on intact endothelium) causes NO release and relaxation but in damaged endothelium, M3 agonism will cause contraction
What are the B2 specific, quick-onset short duration agonists?
What are the B2 specific, slow-onset long duration agonists?
-Salmeterol and Formoterol (used always with steroids)
duration =12 hrs
What are the cholinergic antagonists?
Atropine, Ipratropium, Tiotropium, Imeclidinium
What are the methylxanthines (bronchodilators and antiinflammatory)?
What are the leukotriene receptor blockers (antiinflammatory)?
Monteleukast and Zafirlukast
What are the leukotriene synthesis inhibtiors?
What are the Anti-IgE ABs?
Omalizumab and Dupilumab
What are the Anti-IL-5 ABs?
Mepolizumab and Reslizumab
T or F. Anticholinergic agents will not cause a change in BP when given alone
T. Although there will be M3 binding in the vessels, you will not see a change (there must be a tonic release for change to occur) but you will see some increase in HEART RATE (but not CO)
What is Advair?
Salmeterol + Flucticasone (LABA)
How do B2 agonists work?
It causes increases in cAMP!!
(via Gs), which activate PKA, which phosphorylates Myosin light chain kinase (MLCK), deactivating it, and decreasing muscle contraction OR harbor Ca2+ in the ER AND
cAMP can activate EPAC (exchange protein activated by cAMP) which can reduce bronchial smooth muscle proliferation
T or F. Frequent use of LABA can cause de-sensitivity of the receptor
T. The GCP dissociates
How can B2 agonists stimulate inflammation?
activation via Gq of PLC and B-arrestin-2 (which acts via p38 and PI3K)
Other effects of B2 agonists?
-inhibition of mast cell mediator release (only acutely)
-inhibition of microvascular permeability increase and protein leakage
-increase in mucociliary clearance
How do B2 agonists increase mucociliary clearance?
increasing frequency of cilia beating
What else do LABAs do?
increase transcription of glucocorticoid receptors (and glucocorticoids increase B2 receptor density)
AEs of B2 agonists?
-fall in BP and reflex tachycardia
-Hypokalemia (prolonged QT) AT HIGH DOSE
-agitation, convulsions, coma