Pharmacology - Cholinergic System

Front 1

What are two main TYPES of cholinergic receptors?

Back 1

NICOTINIC
MUSCARINIC

Front 2

Muscarinic receptor subtype primarily associated with the heart:

Back 2

M2

Front 3

Acetylcholine is rapidly inactivated by synaptic
_____.

Back 3

Acetylcholine is rapidly inactivated by synaptic
acetyl-cholinesterase (AChE).

Front 4

Cholinergic drugs mimic or
block the action of _____.

Back 4

Cholinergic drugs mimic or
block the action of Acetylcholine.

Front 5

Effector organs of acetylcholine ?

Back 5

Effector organs:
Smooth muscle
Skeletal muscle
CNS

Front 6

Which type of cholinergic receptor is:
Postsynaptic to preganglionic neurons in all autonomic ganglia including: Chromaffin cells of the adrenal medulla i.e. the perikarya of post ganglionic neurons.

Back 6

Nicotinic receptor (Nn)

Front 7

Cholinergic receptor type primarily localized at skeletal muscle neuromuscular junctions:

Back 7

nicotinic (more specifically Nm)

Front 8

Subtypes of nicotinic receptors?

Back 8

1. N^M Nicotinic muscular receptors – in neuromuscular junction. activation opens cation ch. resulting in end plate depol. and sk. muscle contractions
2. N^N postsynaptic neurons: autonomic ganglia, adrenal medulla (chromaffin cells),
>coupled to activ. of cation ch.
3. CNS
4. presynaptic nerve terminals

Front 9

Name 3 Subtypes of muscarinic receptors?

Where is body are each of these found?

Back 9

M1 - autonomic ganglia, CNS
M2 - Heart (SA node, AV node, atrial)
M3 - smooth muscle, secretory glands

Front 10

Location of different Muscarinic Receptors?

Back 10

1. On post-synaptic membrane of neuro-effector junction innervated by postganglionic parasympathetic neurons
2. On post-synaptic membrane of neuro-effector junction innervated by some postganglionic sympathetic neurons
3. On vascular endothelium - these receptors are pharmacologically important since they are not innervated, their physiological importance is unclear.
4. In autonomic ganglion
5. On pre-synaptic nerve terminal
6. In CNS

Front 11

What receptor is responsible for signal transd. pathway associated with:
stimulation of enzyme phospholypase C and increased cytosolic Ca2+

Back 11

Activation of M1 and M3 receptors -->

stimulation of enzyme phospholipase C and increased cytosolic Ca2+
note: increased uptake of Ca+2 --> depolarization?

Front 12

What receptor is responsible for signal transd. pathway associated with:
associated with activation of K+ channel and inhibition of enzyme adenylyl cyclase.

Back 12

M2 receptor

Front 13

Name 4 directly-acting Cholinergic Agonists (drugs not naturally occurring)

Back 13

Methacholine, Carbachol, and bethanechol, Synthetic Choline esters

Front 14

Methacholine agents show selectivity to what organs?

Back 14

cardiovascular system

Front 15

Carbachol and Bethanechol agents show selectivity to what organs?

Back 15

smooth muscles of the GI tract and urinary bladder

is this associated with M3?

Front 16

* Mild nicotinic, strong MUSCARINIC agonist.
* Has longer duration of action than ACh, since it is hydrolyzed at a slower rate by AChE, moreover it is almost totally resistant to hydrolysis by other cholinesterases.

Back 16

Methacholine

Front 17

* Very potent nicotinic and muscarinic agonist.
* Totally resistant to hydrolysis by AChE and other cholinesterases, therefore long duration of action.
* can stimulate autonomic ganglion and some of its effects can be due to ACh release from terminals of cholinergic fibers.

Back 17

Carbachol (carbamylcholine)

Front 18

* Pure muscarinic agonist
* Used at times in treatment of GI tract atony, and detrusor atony in dog and cats.

Back 18

Bethanechol (Carbamyl-β-methylcholine)

Front 19

Localization of muscarinic cholinergic receptors:?
A. postganglionic parasympathetic effector sites
B. autonomic ganglia cells
C. adrenal medulla
D. A & C
E. A, B & C

Back 19

E. muscarinic cholinergic receptors at all these

Front 20

Highest nicotinic receptor activity among choline esters:
A. acetylcholine
B. atropine
C. methacholine
D. carbachol

Back 20

D. carbachol

Carbachol = very potent nicotinic and muscarinic agonist.

Front 21

Choline ester most susceptible to hydrolysis by acetylcholinesterase:

Back 21

acetylcholine

Front 22

Atony

Back 22

- loss of muscle tone

Front 23

Which directly-acting Cholinergic Agonists are similar in their selectivity?

Back 23

Bethanechol & carbachol

* both somewhat selective for smooth muscles of GI tract and urinary bladder

Front 24

Resistant to hydrolysis by acetylcholinesterase?

Back 24

carbachol
Bethanechol

Front 25

What do these compounds have in common?
Muscarine
Arecoline
Pilocarpine

Back 25

All naturally occurring, direct-acting cholinergic AGONISTS

MAP "Directs u to nature's cholon"

-ine

Front 26

Name naturally occurring alkaloid which is a directly-acting cholinergic agonists
* producing all parasympathomimetic effects
* used topically to reduce intraocular pressure in canine
glaucoma therapy.

Back 26

pilocarpine!!!

- topically to reduce intraocular pressure in canine
glaucoma therapy.
- primarily a muscarinic agonist derived from Pilocarpus plant

Front 27

Diisopropyl-phospho-fluorodate is the prototype for ?

Back 27

Indirect, Irreversible, Cholinergic Agonists

Front 28

Indirect Cholinergic agonists are divided into what 2 groups?

What is their main mode of action?

Back 28

All are cholinesterase inhibitors:
* Anticholinesterases

Divided into two groups
* Reversible inhibitors
* Irreversible inhibitors

Front 29

Indirect, Irreversible, Cholinergic Agonists are used for:

Back 29

* Insecticides
* Dichlorvos (highly volatile organophosphate, widely used as a insecticide) - flea collars, antihelmintic
* Nerve Gas

Front 30

Main side effects are: intense contraction of GI tract accompanied by salivation, nausea and vomiting therefore it should be used with caution. .

Back 30

Bethanechol <-- GI side effects

Front 31

parasympathomimetics example?

Back 31

Muscarinic agonists

a drug or poison that acts by stimulating or mimicking the P.S. nervous system

Front 32

parasympatholytics example?

Back 32

Muscarinic antagonists

Atropine and scopolamine

Front 33

Describe 3 groups of Cholinergic Antagonists (what do they inhibit?)

Back 33

Drugs that interfere with actions of ACh by blocking cholinergic receptors.
Grouped in categories:
1. Anti-muscarinics: for receptors present on PS neuroeffectors and vascular endoth.
2. Ganglionic blockers: for receptor on post-ganglionic neurons
3. Neuro-muscular blockers: for receptors present on motor end plate of skeletal muscles

Front 34

Associated with parasympathetic activation (direct effects):
A. increase heart rate
B. decreased GI motility
C. decrease cardiac contractility
D. urinary retention

Back 34

C. decrease cardiac contractility

parasympathetic effects decrease both heart rate and contractility, mainly atrial contractility

Front 35

Name 2 synthetic anti-muscarinic drugs (atropine-like agents)

Back 35

Pirenzepine
Telenzepine

Front 36

Name this Synthetic anti-muscarinic drug:
Exibits selective for M1 receptors on post-ganglionic neurons of autonomic ganglia.
It reduces gastric acid secretion.
(Ulcer treatment in other country other than the US).

Back 36

Pirenzepine (anti-muscarinic)

It reduces gastric acid secretion.
(Ulcer treatment in other country other than the US).

Front 37

An analogue of pirenzepine (a more selective inhibitor of gastric secretion)

Back 37

Telenzepine

Front 38

What effect does Pirenzepine have gastric acid secretion?

How does it pull this off?

Back 38

* reduces gastric acid secretion by blocking M1 receptors in intramural ganglia of stomach and on gastric entero-chromaffin-like cells

Front 39

Mydriasis?

Back 39

dilation of the pupil

Front 40

Found in bethel nut has some nicotinic activity but is primarily muscarinic and has some CNS effects (stimulation and euphoria).

Back 40

Arecoline (naturally occurring, direct-acting cholinergic AGONISTS)

Front 41

Indirect Cholinergic agonists are reversible inhibitors of _____?

Back 41

Indirect Cholinergic agonists are reversible inhibitors of cholinesterases

Front 42

Name 4 Indirect Cholinergic agonists (REVERSIBLE inhibitors of ChE)

note: ChE = cholinesterase which break down ACh

Back 42

Reversible inhibitors of ChE: physostigmine
pyridostigmine
endrophonium
neostigmine

fyi: 3 end w/-stigmine

Front 43

What clinical application do these reversible cholinesterase inhibitors share?

What distinguishes them?

Back 43

Used in the treatment of myasthenia gravis.

similar pharmacologic action but duration of action different

Front 44

Which indirect cholinergic agonists used for glaucoma, for antimuscarinic poisoning
- atropine toxicity, and is
drug of choice for myasthenia gravis b/c has longer duration of action?
(but discontinued in some circles b/c can cause additional poisoning)

Back 44

Physostigmine: longest duration

Front 45

Name only reversible inhibitors of ChE that does NOT end w/-stigmine??

Back 45

endrophonium

Front 46

Used to reverse neuromuscular
blockade induced by certain neuromuscular blocking agents.

Back 46

Neostigmine

Front 47

Rank 4 indirect ACh agonists based on duration of action (longest to shortest)

Back 47

1. Physostigmine: longest duration
2. Pyridostigmine
3. Neostigmine
4. Endrophonium : shortest duration

Front 48

T/F Both Neostigmine & Physostigmine effective given orally, but Neostigmine easily penetrates BBB (causes CNS effects).

Back 48

False;
Both Neostigmine & Physostigmine effective given orally, but Physostigmine PHYSOSTIGMINE easily penetrates BBB (causes CNS effects).

Front 49

These are example of ?
atracurium
vecuronium
mivacurium
pancuronium

Back 49

Noncompetitive NM blockers are used in vet med:
- skeletal muscle relaxant
- used adjunct. in anesthesia to facil. endotracheal intubation and sk. muscle relaxation during surgery, etc
- inhibit neuron transmission to muscle by blocking NAR?
(nicotinic AcH receptor)

Front 50

What receptor(s) have these effects?
* Phospholipae C stimulation >> increased cytostolic Ca++
* Smooth muscle contraction (M3)
* Secretion of exocrine gland
(Cellular responses)

Back 50

Effects Mediated by M1 and M3 receptor
* Phospholipae C stimulation >> increased cytostolic Ca++

Front 51

Effects Mediated by M2 receptor?

Back 51

M2: Decrease adenylyl cyclase
* Increased K+ channel
* Causes decreased conduction rate >> decreased heart rate

Front 52

selective anti-muscarinic (muscarinic antagonist).
* slow onset of action, does not cross BBB
* less arrhythmogenic
* don't use in horses

Back 52

glycopyrrolate

Front 53

Bronchoconstriction in an asthmatic is treated with?
A. Atropine
B. ACh agonist

Back 53

Atropine

Anticholinergic agents (antimuscarinic) are used in treating asthma, because block bronchioconstriction of PS.
(decr. in PS activity may may decrease brochiolar smooth muscle tone)

Front 54

What compound is a prototype of all directly acting cholinergic agonists?

Back 54

Acetylcholine

Front 55

What compound rapidly inactivates acetylcholine after it is released?

Back 55

synaptic Acetyl-cholinesterase

Front 56

What compounds inactivate non-synaptic acetylcholine?

Back 56

Liver and plasma cholinesterase

Front 57

What enzyme catalyzes the synthesis of acetylcholine from choline and acetate?

Back 57

Choline acetyl transferase

Front 58

What are some subtypes of nicotinic receptors?

Back 58

Nm - Neuromuscular junction
Nn - Autonomic ganglia, adrenal medulla, CNS