Respiratory

Question 1

Define a mucus plug

Answer 1

• SM constriction
• folded epithelium
• hyper mucus secretion
• not reversible by bronchodilator treatment

Question 2

Immediate mast cell mediators?

Answer 2

Histamine
Heparin
Tryptase
TNF-a

Question 3

Rapid mast cell mediators?

Answer 3

Cys-LTs

PGD2

Question 4

Slow mast cell mediators?

Answer 4

Late T cell and eosinophil dependent
IL-4
IL-5
GM-CSF

Question 5

Effects of histamine acting on H1 receptors?

Answer 5

pain and itch
bronchospam
mucus secretion
vasodilation
increased vascular leak
CNS wakefullness

Question 6

Effects of histamine on H2 receptors?

Answer 6

positive inotropic and chronotropic

gastric acid secretion

Question 7

Where do leukotriene receptor antagonists bock?

Answer 7

CysLT1 receptor

Question 8

Effects of Cyc-Leukotrienes?

Answer 8

bronchoconstrictor
vasoactive
leaky vessels

Question 9

Endogenous inhibitors of mast cells

Answer 9

PGE2
adrenaline
cortisol

Question 10

Pharmacological inhibitor of mast cell activation?

Answer 10

monoclonal ABs to a-chain of FceRI

Question 11

Inhibitors of asthma mediator production?

Answer 11

Antihistamines (H1)
GCS
CysLT1 R antagonist
Muscarinic inhibitors

Question 12

Briefly describe airway SM contractile mechanism

Answer 12

• activation of voltage gated Ca channels
• activate PLC and IP3
• release Ca from SR
• Ca binds calmodulin
• activation of MLCK
• actomyosin Atlases activated
• cross bridge cycling

Question 13

Mediators that cause airway SM contraction?

Answer 13

ACh
HA
LTC4
LTD4

Question 14

Mediators that case airway SM relaxation

Answer 14

PGE2
Adrenaline
PGI2

Question 15

T/F Does airway SM activate Rho Kinase and PKC?

Answer 15

False, rho kinase and PKC inhibit MLCK phosphates. this increase MLC/MLC-P ratio decreasing airway SM contraction

Question 16

Pathology of the airway in asthmatics

Answer 16

• goblet cell metaplasia
• sub endothelial collagen thickening
• infiltration of immune cells
• increased mucosal vascularity
• increased smooth muscle volume
• decreased cartilaginous disc

Question 17

Adverse effects of SABAs?

Answer 17

tachycardia
tremor
hypokalemia

Question 18

Mechanism of contraction antagonism by SABAs?

Answer 18

Increased cAMP

Increased PKA (de-phosphorylates MLCK-P, increases SERCA Ca uptake)

Decreased intracellular calcium by inhibiting the IP3R (that promotes Ca release from SERCA)

Question 19

Mechanism of MusR agonism contraction in airway SM?

Answer 19

Mus M3R (GPCR) –> PLC –> IP3 –> IP3R –> SERCA Ca release –> MLCK –> MLCK-P –> cross bridge cycling

Question 20

Are muscarinic antagonist more or less effective in asthma vs COPD?

Answer 20

More effective in COPD

Question 21

Describe GCS transrepression

Answer 21

monomer GCS+GR inhibit NFKb activation in the cytoplasm

Question 22

Describe GCS transactivation

Answer 22

homodimer GCS+GR –> nucleus –> ↑GILZ (↓NFkB), ↑MKP1 (↓AP-1)

Question 23

Side effects of oral GCS

Answer 23

• osteoporosis
• diabetes
• muscle wasting
• hypertension
• growth suppression
• weight gain

Question 24

Mechanism of theophylline?

Answer 24

• PDE inhibition/smooth muscle relaxant
• Adenosine antagonism
• HDAC2 activation (transrepressive steroid action)

Question 25

Mechanism of PDE inhibitors?

Answer 25

Prevent the breakdown of cAMP (acts on PKA to increase Ca uptake by SERCA and inhibits IP3R) and cGMP (increased PKA - same pathway)