Pharmacology Flashcards
Control of bronchiole smooth muscle
sympathetic/ para sympathetic control
Sympathetic control function
bronchodilation
opens airways
greater air influx - fight/ flight
Sympathetic control mechanism
Short pre (ACh + nicotinic), long post, noradrenaline
Innervates adrenal gland
- secretes adrenaline
adrenaline + Beta 2 receptor
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)
Phosphodiesterase
enzyme
- catalyses cAMP -> 5’AMP
- inhibits PKA activity
Parasympathetic control function
bronchoconstriction
Parasympathetic control mechanism
long pre (ACh, nicotinic) short post (ACh - muscarinic M3 receptor)
M3 muscarinic receptor agonist
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
SABAs
short acting Beta 2 agonists
- salbutamol
- innervate Beta 2 receptors
- bronchodilation
- prn
LABAs
long acting beta 2 agonists - formoterol + salmeterol innervate beta 2 receptors bronchodilation twice daily - prophylactic
SAMAs
short acting muscarinic antagonists
- antagonise M3 receptors
prevent bronchoconstriction
- Ipratropium
LAMAs
Long acting muscarinic antagonists
- antagonise M3 receptors
- prevent bronchoconstriction
- Tiotropium
Examples of inhaled glucocorticoids
Beclometasone dipropionate (BDP), Budesonide + fluticasone
Mechanism of corticosteroids
Lipophilic
- bind to GR alpha receptors in cytoplasm
- form homomers
increased transcription of anti-inflammatory genes
decreased transcription of inflammatory proteins
Glucocorticoid steroid effect
- Decreased: cytokine production
mast cell + eosinophil influx
activation of CD4+
Stabilises airway
Oral glucocorticoid example
prednisolone
Features of prednisolone
- Good when airway very obstructed, low uptake of inhaled
- Low therapeutic ratio
2 week trial -> inhaled
Cysteinyl Leukotriene Receptor Antagonists
- Montelukast + Zafirlukast
- Prevent bindings of leukotrienes
anti inflammatory effect - bronchodilation
Prevents oedema + mucous hypersecretion
prevents eosinophil influx
Cromones
Supress histamine secretion
- cromoglicate
poor efficacy
asthma only
Methyl xanthines
Theophylline
- inhibit phosphodiesterase
increased PKA activity
Anti IgE treatment
Omalizumab - prevents mast cell activation - decreased histamine, IL 5 + IL13 secretion very expensive - severe + persistent asthma only
Anti IL 5
Mepolizumab
Blocks effect of IL-5
prevents eosinophil influx
- expensive
Anti IL4 alpha
Dupilumab
prevents IL-4 + IL-13 binding
- decreased eosinophil influx, IgE production airway hypersensitivity
Mucolytics
Carbocisteine
- COPD only
decrease mucous viscosity
