Pharmacology

Question 1

Parasympathetic division:

Location of pre and post ganglionic fibres

Answer 1

Pre ganglionic fibres: located in the brainstem

Post ganglionic fibres: locates in the walls of the bronchioles

Question 2

Parasympathetic division:

Stimulation of post ganglionic cholinergic fibres

Answer 2

Bronchial smooth muscle contraction (mediated by M3 muscarinic ACh receptors on ASM)

Increased mucous secretion (mediated by M3 muscarinic ACh receptors on gland cells)

Question 3

Parasympathetic division:

Stimulation of post-ganglionic non-cholinergic fibres

Answer 3

Bronchial smooth muscle relaxation (mediated by NO and VIP)

Question 4

Sympathetic division:

Location of pre and post ganglionic fibres?*

Answer 4

No post ganglionic innervation of bronchial smooth muscle.

Post ganglionic fibres supply sub-mucosal glands and smooth muscle of blood vessels instead.

Question 5

Sympathetic division:

Stimulation of post ganglionic fibres

Answer 5

Bronchial smooth muscle relaxation (via B2-adrenoceptors on ASM cells activated by adrenaline)

Decreased mucous secretion (mediated by B2-adrenoceptors on gland cells)

Increased mucocillary clearance (mediated by B2-adrenoceptors on epithelial cells)

Vascular smooth muscle contraction (mediated by a1-adrenoceptors on vascular smooth muscle cells)

Question 6

Contraction mechanisms in smooth muscle

Answer 6

GPCR is activated
GPCR couples with Gq11
PIP2 -> IP3
IP3 travels to IP3 receptor (on SR) 
When this occurs, Calcium stored in the SR floods out into the cytoplasm and we get contraction

Question 7

Contraction by calcium in smooth muscle

Answer 7

The Ca2+ now in the cytoplasm binds to calmodulin and activates it through a conformational change Ca-calmodulin.
This converts inactive MLCK -> active MLCK
Active MLCK becomes phosphorylated and inactive myosin becomes active myosin
Actin and myosin filaments can now slide over each other and cause contraction

Question 8

Relaxation of smooth muscle

Answer 8

Dephosphorylation of MLCK so that contraction can’t occur

Adrenaline activates B2 adrenoceptor
This couples with Gs and activates AC
ATP + AC -> cAMP
cAMP activates PKA
- phosphorylats and inhibits MLCK (inhibits contraction)
- phosphorylates and stimulates myosin phosphatase (facilitates relaxation)
Inhibit PDE increases cAMP

Question 9

M1 ACh receptors

Answer 9

Facilitate fast neurotransmission mediated by ACh acting on nicotinic receptors

Question 10

M2 ACh receptors

Answer 10

Act as inhibitory auto receptors, reducing the release of ACh.
We don’t want to block this in COPD

Question 11

M3 ACh receptors

Answer 11

Mediate contraction to ACh
Stimulate the release of ACh
We want to block M3 in COPD