drugs acting at the parasympathetic system

Question 1

What 5 things does the parasympathetic nervous system

Answer 1

• salivation
• slowed HR
• bronchoconstriction and stimulation of mucus secretion
• increased motility and secretion of gut
  – contraction of detrusor muscle, relaxation of sphincter, which causes micturition

Question 2

In neurotransmission in the parasympathetic nervous system, what are the pre and post neurons and the synapse called?

Answer 2

• Pre neurone: preganglionic neuron
• Post neurone: post ganglionic neuron
• Synapse: ganglion

Question 3

What receptors are found on the postganglionic neuron in the parasympathetic nervous system?

Answer 3

• nicotinic acetylcholine receptors

Question 4

What receptors are found on the target organ (heart, salivary gland, airways etc) in the parasympathetic nervous system?

Answer 4

muscarinic acetylcholine receptors

Question 5

What type of receptor is a nicotinic acetylcholine receptor and what does it allow

Answer 5

• a type of ligand gated ion channel receptor
• allows fast neurotransmission

Question 6

Outline reuptake of ACh at target organs in the parasympathetic nervous system

Answer 6

1. Ach unbinds from muscarinic acetylcholine receptors
2. Acetylcholine-esterase converts ACh to acetyl and choline
3. transported protein moves choline into back into the neurone cell where it reacts again to form ACh

Question 7

What do muscarinic acetylcholine receptors look like and where do agonists/antagonists bind

Answer 7

• have 7 transmembrane helices
• agonists/antagonists bind IN BETWEEN helices

Question 8

where are G proteins bound in muscarinic acetylcholine receptors

Answer 8

G protein are bound on intracellular face of receptor

Question 9

what happens when an agonist binds to a muscarinic acetylcholine receptor

Answer 9

• changes conformation of receptor slightly, causing rods/helices to rotate, transmitting the energy to the G protein, activating it.

Question 10

Outline intracellular signalling for muscarinic acetylcholine receptors

Answer 10

1. ACh binds to GPCR
2. Gq ( a type of G protein) is activated that then unbinds from transmembrane proteins and binds to Phospholipase C (PLC).
3. PLC conversts PIP2 to IP3 and DAG
4. IP3 binds to IP3 receptors and causes calcium to be released from Sacroplasmic recticulum into the cytosol
5. Calcium causes contraction through activation of myosin light chain kinase (MLCK)

Question 11

what will agonist activation of muscarinic receptors in the parasympathetic nervous system do?

Answer 11

ALL the affects of the Parasympathetic nervous system:

• salivation
• decreased HR
• bronchoconstriction + stimulation of mucus secretion
• increased gut motility and stimulation of secretion in the gut
• contraction of the detrusor muscle, thus relaxation of the sphincter and thus micturition

Question 12

What 3 drugs are used as muscarinic acetylcholine receptor agonists

Answer 12

• ACh (naturally occurring)
• muscarine (not used anymore)
• pilocarpine

Question 13

What 3 drugs are used as muscarinic receptor antagonists

Answer 13

• Atropine
• Ipratropium
• Tiotropium

Question 14

What is a benefit of atropine and why can this benefit sometimes be a detriment in clinical use

Answer 14

• crosses membranes easily
• can be an issue because it can go in the body and cause effects at all muscarinic receptors in the body, so can cause unwanted side effects

Question 15

Why is ipratropium and tiotropium better to use

Answer 15

are charged so don’t cross membranes as easily, so are more selective about the membranes they cross

Question 16

What type of antagonist is atropine

Answer 16

competitive antagonist

Question 17

Outline how symptoms change as atropine concentration increases

Answer 17

at low doses you get dry mouth but as you get higher doses you start to get symptoms like difficulty in micturition.

this is believed to happen because in different organs there is different amounts of ACh being released, so more levels of atropine needed to compete with ACh levels

Question 18

how can you reduce side effects of agonists in the parasympathetic nervous system

Answer 18

through route of administration (i.e inhalers for bronchodilation)

Question 19

what drug is used for Myasthenia gravis and what type of drug is it

Answer 19

• neostigmine
• it is an Acetylcholine-esterase inhibitor

Question 20

what type of inhibitor are poisons

Answer 20

irreversible inhibitors of acetylcholine-esterase

Question 21

what drug can reverse the binding of poisons/irreversible inhibitors but only if given soon after the poison has been administered

Answer 21

pralidoxime