3 L3 Parasympathetic Nervous System Pharmacology

Question 1

What receptors does Ach bind to

Answer 1

Ligand gated ion - GPCRS (Gi and Gq)

Question 2

Does Ach have higher affinity for muscarinic or nicotinic receptors

Answer 2

Muscarinic

Question 3

Ach muscarinic receptors

Answer 3

mAchR 1, 3, 5- Stimulatory Gq
mAchR 2, 4- Inhibitory Gi

Question 4

Ach stimulation of parasympathetic and sympathetic NS

Answer 4

Directly stimulates parasympathetic- Indirectly stimulates sympathetic

Question 5

Ach in the parasympathetic NS

Answer 5

Activates nicotinic receptors in ganglion - Activates muscarinic receptors at target tissues

Question 6

Ach in the sympathetic NS

Answer 6

Activates nicotinic receptors in ganglion - NA/NE activates a and B receptors in target organs - nAchR activation in adrenal gland leads to systemic release of NE/NA and adrenaline

Question 7

Way to remember muscarinic receptor types

Answer 7

Odds- Gq stimulatory
Evens- Gi inhibitory

Question 8

M1

Answer 8

Found in brain, salivary glands, tear ducts

Question 9

M3

Answer 9

Found in GI smooth muscle

Question 10

M5

Answer 10

Found in brain and eye

Question 11

M2

Answer 11

Found in heart and brain

Question 12

M4

Answer 12

Found in brain

Question 13

M3 activation

Answer 13

Activates PLC - Produces DAG and IP3 - Increases intracellular Ca - Initiates smooth muscle contraction (rest and digest)

Question 14

M2 activation

Answer 14

Decreases cAMP activity - Prevents PKA from activating Ca channels - Decrease in hear contractility - Decreases heart rate

Question 15

M4 activation and schizophrenia

Answer 15

Schizophrenia is caused by too much dopamine release in VTA - M4 receptors inhibit neurons from firing - M4 receptors prevent release of Ach - Less activation of nicotinic receptors - Less depolarisation of dopaminergic neurons in VTA - decreases schizophrenia symptoms

Question 16

nAchR at NMJ

Answer 16

Connects CNS to skeletal muscle - Composed of nAchR with unique combination of protein subunits- allows for drug targeting at NMJ

Question 17

NM depolarising block

Answer 17

nAchR agonist
Phase 1- Sustained activation/depolarisation
Phase 2- nAchR becomes desensitised, closing the channel

Question 18

NM non-depolarising block

Answer 18

nAchR antagonist- Competitive antagonist

Question 19

nAchR desensitisation

Answer 19

Prolonged opening of nAchR leads to extended depolarisation - Ca is taken up by ER - Muscle relaxation occurs

Question 20

Ach breakdown

Answer 20

Ach is degraded by acetylcholinesterase (AchE) into choline and acetate

Question 21

AchE inhibitor (donazepil)

Answer 21

Reduced Ach breakdown- increased Ach at synapse - Similar affects to AchR agonists (but increases Ach at all AchRs)

Question 22

What are AchE inhibitors used for

Answer 22

Alzheimers disease - Reversal of muscle relaxants (increases Ach at synapse)

Question 23

2 main neurotransmission pathways for alzheimers treatment

Answer 23

Glutamate antagonists at NDMA receptors - AchE inhibitors e.g. donazepil

Question 24

Drug effects on alzheimers

Answer 24

They reduce symptoms but not disease progression

Question 25

How do AchE inhibitors affect hippocampus activity

Answer 25

They increase hippocampus activity- can reduce symptoms of memory loss

Question 26

Describe irreversible AchE inhibitors

Answer 26

Include highly potent poisons e.g. Insecticide poisoning (organophosphates) Parasympathetic effects first (due to Ach affinity for mAchR) Sympathetic effects next (Ach increases at pre-ganglionic synapse)