Lecture 7 (Drugs Targeting Nicotinic & Muscarinic Receptors) Flashcards Preview

Med Chem > Lecture 7 (Drugs Targeting Nicotinic & Muscarinic Receptors) > Flashcards

Flashcards in Lecture 7 (Drugs Targeting Nicotinic & Muscarinic Receptors) Deck (54):
1

For the sympathetic system the preganglionic neurotransmitter is ___

Ach

2

For the sympathetic system the preganglionic receptors are ?

nicotinic ganglionic (NG)

3

For the sympathetic system the post ganglionic is ___

NA or NE (same chemical)

4

For the sympathetic system the post ganglionic receptors are ?

Adrenergic
(alpha 1, beta 1, beta 2)

5

For the parasympathetic system the preganglionic neurotransmitter is ___

Ach

6

For the parasympathetic system the preganglionic receptors are ?

nicotinic ganglionic (NG)

7

For the parasympathetic system the postganglionic neurotransmitter is ___

Ach

8

For the parasympathetic system the postganglionic receptors are ?

Muscarinic (M)

9

The somatic nervous system is ____ controlled.

consciously

10

Neurotransmitter for somatic nervous system is ?

ACh

11

Receptors for somatic nervous system are ?

nicotinic cholinergic (NM)

12

Explain the synapse for ACh

-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

13

ACh has what two groups on it?

ester
amine

14

AChE ____ Ach

hydrolyzes

(it chops the ester bond

15

When AChE hydrolyzes Ach, what are the two products?

acetic acid and choline

16

All cholinergic receptors bind ___ for activity

ACh

17

two types of cholinergic receptors?

nicotinic
muscarinic

18

What two types of nicotinic receptors are there?

NG - nicotinic ganglionic
NM - nicotinic cholinergic

19

How many types of muscarinic receptors are there?

5

M1-M5

20

All muscarinic receptors are _____

GPCRs

21

Nicotinic acetylcholine receptors us a ___ ion channel

sodium (Na+)

22

How does the nicotinic acetylcholine receptor work?

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

23

2 examples of NM agonists

succinylcholine
decamethonium

24

2 examples of NM antagonists

pancuronium
d-tubocurarine

25

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

muscle relaxation during surgery

26

Succinylcholine is rapidly hydrolyzed by _____

esterases

27

Pancuronium has a ____ duration of action than succinylcholine

longer

28

2 examples of NG selective antagonists

trimetaphan
hexamethonium

29

M1 receptor affects G alpha __

q

30

M2 receptor affects G alpha __

i

31

M3 receptor affects G alpha __

q

32

M1 = _____

excitation

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

33

M2 = _____

inhibition

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

34

M3 = ______

excitation

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

35

M1 reaches which tissue locations?

CNA (cortex hippocampus)
ganglia
parietal cells

36

M2 reaches which tissue locations?

cardiac - atria and conducting tissue
neural - presynaptic terminals

37

M3 reaches which tissue locations?

smooth muscle
vascular
endothelium

38

M1 function

CNS excitation (memory)
gastric acid secretion
GI motility

39

M2 function

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

40

M3 function

smooth muscle contraction (bladder)

41

What does removing methyl groups on Ach do?

reduces potency

42

On ACh what is required for activity

N+

43

is the ACh molecule flexible?

yes

44

Receptors for ACh have 2 sites - what are they?

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

45

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

5

46

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

7

47

Carbonyl on ACh is a strong __________

electrophile

48

ACh is very susceptible to _______

hydrolysis

49

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

methyl group = steric shield

-reduces access to carbonyl carbon by nucleophiles also sterically inhibits binding to AChE

50

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

carbachol

51

_____ and _____ are not orally active and not useful clinically

ACh
Carbachol

52

What is ethacholine used for?

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

53

What is Bethanechol used for?

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

54

What is Pilocarpine used for?

treats glaucoma