Lecture 7 (Drugs Targeting Nicotinic & Muscarinic Receptors)

Question 1

For the sympathetic system the preganglionic neurotransmitter is ___

Answer 1

Ach

Question 2

For the sympathetic system the preganglionic receptors are ?

Answer 2

nicotinic ganglionic (NG)

Question 3

For the sympathetic system the post ganglionic is ___

Answer 3

NA or NE (same chemical)

Question 4

For the sympathetic system the post ganglionic receptors are ?

Answer 4

Adrenergic

alpha 1, beta 1, beta 2

Question 5

For the parasympathetic system the preganglionic neurotransmitter is ___

Answer 5

Ach

Question 6

For the parasympathetic system the preganglionic receptors are ?

Answer 6

nicotinic ganglionic (NG)

Question 7

For the parasympathetic system the postganglionic neurotransmitter is ___

Answer 7

Ach

Question 8

For the parasympathetic system the postganglionic receptors are ?

Answer 8

Muscarinic (M)

Question 9

The somatic nervous system is ____ controlled.

Answer 9

consciously

Question 10

Neurotransmitter for somatic nervous system is ?

Answer 10

ACh

Question 11

Receptors for somatic nervous system are ?

Answer 11

nicotinic cholinergic (NM)

Question 12

Explain the synapse for ACh

Answer 12

• action potential
• this opens calcium channels which acts as a stimulus for Ach to leave presynaptic cell and go into the synaptic cleft
• Ach then attaches to Ach receptors on post synaptic cell
• while in presynaptic cleft, Ach can be broken down by AChE into acetate + choline
• choline can be reuptaked into the presynaptic cell and added to AcCoA to make Ach

*see slide 6 for diagram

Question 13

ACh has what two groups on it?

Answer 13

ester

amine

Question 14

AChE ____ Ach

Answer 14

hydrolyzes

(it chops the ester bond

Question 15

When AChE hydrolyzes Ach, what are the two products?

Answer 15

acetic acid and choline

Question 16

All cholinergic receptors bind ___ for activity

Answer 16

ACh

Question 17

two types of cholinergic receptors?

Answer 17

nicotinic

muscarinic

Question 18

What two types of nicotinic receptors are there?

Answer 18

NG - nicotinic ganglionic

NM - nicotinic cholinergic

Question 19

How many types of muscarinic receptors are there?

Answer 19

5

M1-M5

Question 20

All muscarinic receptors are _____

Answer 20

GPCRs

Question 21

Nicotinic acetylcholine receptors us a ___ ion channel

Answer 21

sodium (Na+)

Question 22

How does the nicotinic acetylcholine receptor work?

Answer 22

Ach binds to ion channel which opens the ion channel and allows Na+ to pass through

Question 23

2 examples of NM agonists

Answer 23

succinylcholine

decamethonium

Question 24

2 examples of NM antagonists

Answer 24

pancuronium

d-tubocurarine

Question 25

Although succinylcholine and pancuronium work via different mechanisms, they are used clinically for the same thing: which is?

Answer 25

muscle relaxation during surgery

Question 26

Succinylcholine is rapidly hydrolyzed by _____

Answer 26

esterases

Question 27

Pancuronium has a ____ duration of action than succinylcholine

Answer 27

longer

Question 28

2 examples of NG selective antagonists

Answer 28

trimetaphan | hexamethonium

Question 29

M1 receptor affects G alpha __

Answer 29

q

Question 30

M2 receptor affects G alpha __

Answer 30

i

Question 31

M3 receptor affects G alpha __

Answer 31

q

Question 32

M1 = _____

Answer 32

excitation +PLC increase IP3 and DAG increase [Ca2+] intracellular decrease K+ outflow

Question 33

M2 = _____

Answer 33

inhibition -AC decrease cAMP decrease [Ca2+] intracellular increase K+ outflow

Question 34

M3 = ______

Answer 34

excitation +PLC increase IP3 and DAG increase [Ca2+] intracellular decrease K+ outflow

Question 35

M1 reaches which tissue locations?

Answer 35

CNA (cortex hippocampus) ganglia parietal cells

Question 36

M2 reaches which tissue locations?

Answer 36

cardiac - atria and conducting tissue | neural - presynaptic terminals

Question 37

M3 reaches which tissue locations?

Answer 37

smooth muscle vascular endothelium

Question 38

M1 function

Answer 38

CNS excitation (memory) gastric acid secretion GI motility

Question 39

M2 function

Answer 39

``` cardiac inhibition decrease HR decrease force of contractility presynaptic inhibition neural inhibition ```

Question 40

M3 function

Answer 40

smooth muscle contraction (bladder)

Question 41

What does removing methyl groups on Ach do?

Answer 41

reduces potency

Question 42

On ACh what is required for activity

Answer 42

N+

Question 43

is the ACh molecule flexible?

Answer 43

yes

Question 44

Receptors for ACh have 2 sites - what are they?

Answer 44

``` anionic site (can accommodate two methyl groups and has a - change binding site) esteratic site (ester O acts as H bond acceptor) ```

Question 45

For muscarinic agonists, as the length of the alkyl chain increases beyond _ atoms, intrinsic activity and affinity decrease

Answer 45

5

Question 46

>_ atoms usually have no activity or affinity (muscarinic agonists)

Answer 46

7

Question 47

Carbonyl on ACh is a strong __________

Answer 47

electrophile

Question 48

ACh is very susceptible to _______

Answer 48

hydrolysis

Question 49

What does adding a methyl group to ACh do? (it is now methacholine)

Answer 49

methyl group = steric shield -reduces access to carbonyl carbon by nucleophiles also sterically inhibits binding to AChE

Question 50

_______ has delocalized electrons on the acetyl group which decreases the electrophilic nature of the carbonyl carbon - makes it resistant to hydrolysis by AChE

Answer 50

carbachol

Question 51

_____ and _____ are not orally active and not useful clinically

Answer 51

ACh | Carbachol

Question 52

What is ethacholine used for?

Answer 52

- used as a test for asthma | - called the methacholine challenge test

Question 53

What is Bethanechol used for?

Answer 53

- increase urinary output - used often after surgery - or used in prostatic hypertrophy that does not respond to convention treatments like Tamsulosin

Question 54

What is Pilocarpine used for?

Answer 54

treats glaucoma