Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
24 Cards in this Set
- Front
- Back
|
definition of asthma
|
a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness
|
|
|
what are the inflammatory effects of asthma
|
- mucus hypersecretion and hyperplasia
- vasodilation - plasma leak - oedema - epithelial shedding - bronchoconstriction - SM hypertrophy, hyperplasia - subepithelial fibrosis - sensory nerve activation |
|
|
what effects are controlled with relievers, controllers and preventers
|
- airway SM bronchoconstriction - treated with relievers, controllers and preventers
- bronchial wall oedema and mucus hypersecretion - can only be treated with prenters |
|
|
what holds the small airways open
|
parenchymal tethering
- stretch further opposes shortening of SM |
|
|
mechanism of airways SM bronchoconstriction
|
increase in calcium -> binds to calmodulin -> activates myosin light chain kinase to phosphorylate myosin light chain -> activation of actomyosin ATPase --> myosin- actin crosslinking and contraction
|
|
|
endogenous mediators for airway smooth muscle contraction
|
- ACh
- histamine - Leukotrienes - LTC4 and LTD4 |
|
|
endogenous mediators for airway smooth muscle relaxation
|
- adrenaline
- PGE2 - PGI2 |
|
|
what mechanisms increase free intracellular calcium
|
- voltage gated calcium channels
- phospholipase C/inositol trisphosphate - releases from intracellular stores |
|
|
mechanisms decreasing free intracellular calcium
|
- plasma Ca ATPase - extrusion across the plasma membrane
- Sarcoplasmic SERCA - uptake into internal stores |
|
|
regulation of airway smooth muscle contraction performed by
|
- protein kinase A - activates myosin light chain phosphatase
- Rho kinase - inhibits myosin light chain phosphatase - protein kinase c - inhibits myosin light chain phosphatase |
|
|
histological changes of an asthmatic epithelial cell
|
- goblet cell metaplasia
- subepithelial collagen thickening of BM - infiltration of inflammatory cells - increased mucosal vascularity - increased smooth muscle volume - epithelial damage |
|
|
drugs that are SABAs
|
salbutamol
terbutaline |
|
|
onset of SABAs
|
rapid - 2-5 minutes
|
|
|
adverse effects of SABAs
|
tachycardia, tremor, hypokalemia
|
|
|
duration of action of SABAs is dependent on
|
perfusion of the lung - not by metabolism
|
|
|
How do SABAs work
|
activate B2 adrenoceptor - activates Gs - stimulates cAMP --> activates PKA:
- activates SERCA - inhibits IP3R Leads to reduced cytoplasmic Ca and therefore less MLCK activation |
|
|
drugs that are LABAs
|
salmeterol - slow onset, 12 hour duration
formoterol - rapid onset, 12 hour duration indacaterol - rapid onset, 24 hour duration |
|
|
when do you use LABAs on patients
|
in combination with GCS
- used as monotherapy - linked to increased morbidity and mortality |
|
|
regulation of beta-2 adrenoceptors achieved by: (3)
|
- phosphorylation (seconds)
- sequestration (minutes) - downregulation (hours) |
|
|
how is phosphorylation of beta-2 adrenoceptor achieved
|
by PKA and beta adrenergic receptor kinase
- also enhances binding of B-arrestin |
|
|
what happens to the B2 adrenoceptor one sequestrated
|
either dephosphorylated and recycled or degraded and lost
|
|
|
how is the B2 adrenoceptor downregulated
|
- decreased mRNA stability
- receptor protein degradation - decreased rate of transcription |
|
|
what are examples of muscarinic receptor antagonists used in asthma
|
ipratropium bromide - non selective
tiotropium bromide - M3 selective |
|
|
action of muscarinic receptor antagonists
|
prevent manifestations of reflex airway obstruction - less effective than beta-2 agonists
|
