Pharmacology

Question 1

Control of bronchiole smooth muscle

Answer 1

sympathetic/ para sympathetic control

Question 2

Sympathetic control function

Answer 2

bronchodilation
opens airways
greater air influx - fight/ flight

Question 3

Sympathetic control mechanism

Answer 3

Short pre (ACh + nicotinic), long post, noradrenaline
Innervates adrenal gland
- secretes adrenaline

Question 4

adrenaline + Beta 2 receptor

Answer 4

beta 2 receptor activated
- Gs alpha sub unit activates Adenylyl Cyclase
- catalyses ATP -> cAMP
- cAMP activates Protein Kinase A
phosphorylates MLCK (inhibits) + myosin phosphatase (stimulates)

Question 5

Phosphodiesterase

Answer 5

enzyme

• catalyses cAMP -> 5’AMP
• inhibits PKA activity

Question 6

Parasympathetic control function

Answer 6

bronchoconstriction

Question 7

Parasympathetic control mechanism

Answer 7

long pre (ACh, nicotinic) short post (ACh - muscarinic M3 receptor)

Question 8

M3 muscarinic receptor agonist

Answer 8

M3 receptor agonist 
- activates Gq/11 alpha sub unit 
- Activates Phosphlipase C 
- catalyses PIP2 -> IP3 
- IP3 activates IP3 receptor 
Ca2+ influx 
- voltage gated Ca2+ 
- Ca2+ gated 2+ channels 
Ca2+ + calmodulin 
activated MLCK 
MLC phosphorylated 
myosin heads bind to actin

Question 9

SABAs

Answer 9

short acting Beta 2 agonists

• salbutamol
• innervate Beta 2 receptors
• bronchodilation
• prn

Question 10

LABAs

Answer 10

long acting beta 2 agonists 
- formoterol + salmeterol 
innervate beta 2 receptors 
bronchodilation
twice daily 
- prophylactic

Question 11

SAMAs

Answer 11

short acting muscarinic antagonists
- antagonise M3 receptors
prevent bronchoconstriction
- Ipratropium

Question 12

LAMAs

Answer 12

Long acting muscarinic antagonists

• antagonise M3 receptors
• prevent bronchoconstriction
• Tiotropium

Question 13

Examples of inhaled glucocorticoids

Answer 13

Beclometasone dipropionate (BDP), Budesonide + fluticasone

Question 14

Mechanism of corticosteroids

Answer 14

Lipophilic
- bind to GR alpha receptors in cytoplasm
- form homomers
increased transcription of anti-inflammatory genes
decreased transcription of inflammatory proteins

Question 15

Glucocorticoid steroid effect

Answer 15

• Decreased: cytokine production
  mast cell + eosinophil influx
  activation of CD4+
  Stabilises airway

Question 16

Oral glucocorticoid example

Answer 16

prednisolone

Question 17

Features of prednisolone

Answer 17

• Good when airway very obstructed, low uptake of inhaled
• Low therapeutic ratio
  2 week trial -> inhaled

Question 18

Cysteinyl Leukotriene Receptor Antagonists

Answer 18

• Montelukast + Zafirlukast
• Prevent bindings of leukotrienes
  anti inflammatory effect
• bronchodilation
  Prevents oedema + mucous hypersecretion
  prevents eosinophil influx

Question 19

Cromones

Answer 19

Supress histamine secretion
- cromoglicate
poor efficacy
asthma only

Question 20

Methyl xanthines

Answer 20

Theophylline
- inhibit phosphodiesterase
increased PKA activity

Question 21

Anti IgE treatment

Answer 21

Omalizumab 
- prevents mast cell activation 
- decreased histamine, IL 5 + IL13 secretion 
very expensive 
- severe + persistent asthma only

Question 22

Anti IL 5

Answer 22

Mepolizumab
Blocks effect of IL-5
prevents eosinophil influx
- expensive

Question 23

Anti IL4 alpha

Answer 23

Dupilumab
prevents IL-4 + IL-13 binding
- decreased eosinophil influx, IgE production airway hypersensitivity

Question 24

Mucolytics

Answer 24

Carbocisteine
- COPD only
decrease mucous viscosity

Question 25

Inhalers pros

Answer 25

• delivery to tissue
• Rapid absorption
• Lower dose required, less side effects
• Good distribution to target tissue
• spacers used to make easier

Question 26

Inhaler cons

Answer 26

• Hard to use
  incorrect inhalation, ineffective treatment
• compliance

Question 27

spacers

Answer 27

reduce speed + particle size
allow drug to be distributed to smallest bronchioles
- greater effect

Question 28

pros/ cons oral medication

Answer 28

greater systemic conc., more side effects

taken when airway is compromised