COPD- pharmacology Flashcards
Describe the muscarinic acetylcholine receptors present in the airways. (Include where they are situated and their function).
M1: Present at ganglia
facilitate transmission mediated by Ach acting on nicotinic receptors.
M2: Present on the post-ganglionic neurone terminals.
These act as inhibitory autoreceptors that reduce ACh release, when acted back on by previously released ACh.
M3: Present on smooth muscle and on mucous secreting cells.
Cause increased smooth muscle contraction and increased mucous secretion.
Describe how activation of M3 receptors causes contraction of airway smooth muscle.
The M3 receptor is a G-protein coupled receptor, coupled to Gq/11. Activation of Gq/11 stimulates phospholipase C, which increases production of inositol triphosphate (IP3) from phosphatidylinositol bisphosphate (PIP3). Increased IP3 causes Ca2+ to be released from the sarcoplasmic reticulum. Further intermediate steps lead to contraction of the smooth muscle cell.
Name 2 SAMAs.
Ipratropium
Oxitropium.
Name 2 LAMAs.
Tiotropium
Aclidinium
a) How are muscarinic acetylcholine receptor antagonists delivered?
b) How is systemic absorption of ipratropium and tiotropium reduced?
a) By the inhalation route
b) They have a quaternary ammonium group attached.They are therefore charged and cannot be absorbed by the epithelium.
How to muscarinic acetylcholine receptor antagonists reduce bronchoconstriction?
Irritant stimuli initiate a vagal reflex which liberates ACh.
The SAMAs and LAMAs reduce the brochospasm caused by this.
They also block ACh- mediated basal tone.
They reduce mucous secretion.
Do SAMAs/LAMAs have any effect on the development of COPD?
Not really- their effect is mainly palliative.
Is a) ipratropium and b) tiotropium selective or non selective? If selective, for which receptor?
c) For the selective drug, what makes it more selective than the other?
d) Is there another drug which exhibits similar selectivity?
a) Non-selective
b) Selective for M3 receptors.
c) Tiotropium has a greatly longer half life at the M3 receptor than Ipratropium.
d) Yes- aclinidium.
Describe Beta 2 agonist treatment of COPD.
SABA: salbumatol
LABA: salmeterol and formoterol.
Ultra LABA: indacaterol (acts much more quickly)
a) Name a phosphodiesterase 4 inhibitor.
b) How do these work?
a) Rofumilast.
b) PDE4 is the prominant PDE expressed in neutrphils, T cells and macrophages. Therefore inhibition of PDE4 may have inhibitory effects on inflammatory and immune cells.
