ANS Harvey Part 4

Question 1

(balnk) is the only endogenous neurotransmitter acting at cholinergic receptors.

Answer 1

Acetylcholine (ACh)

Question 2

(blank) are exogenous compounds that imitate functional responses associated with parasympathetic stimulation.

Answer 2

parasympathomimetics

Question 3

(blank) are exogenous compounds that imitate functional responses produced by acetylcholine (ACh) at cholinergic receptors.

Answer 3

Cholinomimetics

Question 4

(blank) are compounds that block cholinergic transmission at involving muscarinic receptors (antimuscarinics), neuronal nicotinic receptors (ganglionic blockers) or the neuromuscular junction (neuromuscular blockers).

Answer 4

Cholinergic Antagonists

Question 5

To know what kinds of cholinomimetics responses you can get you must know what?

Answer 5

what type of receptor is involved
what type of cell/tissue is involved
the signaling pathway activated by receptor
whether effect is direct or indirect

Question 6

Odd number receptors of cholinergic receptors are what kind of G proteins?

Answer 6

Gq

Question 7

even number receptors of cholinergic receptors are what kind of G proteins?

Answer 7

Gi/o

Question 8

How does Muscarine receptors 1/3/5 work?

Answer 8

by PLC, IP3->Ca2+ which creates smooth muscle contraction and vascular relaxation, and exocrine gland secretion

Question 9

How does muscarine receptors 2/4 work?

Answer 9

by inhibiting AC and increasing potassium and creating relaxation, slow heart rate

Question 10

What are the ways to get excitation?

Answer 10

Na+ in, little K/Cl out

Question 11

HO do you get a nictoninc muscle receptor to work>

Answer 11

you increase Na+ and get skeletal muscle and nerve excitation

Question 12

What kind of receptor is pentameric?

Answer 12

nicotinic receptors

Question 13

What kind of receptor is this?
Ligand-gated ion channels

Exist as pentamers containing one or more of 5 different subunits (α β γ δ ε).

There are 9 α subunit isoforms (α1- α9) and 5 β subunit isoforms (β1- β5).

has at least two α subunits, where ACh binds.

Answer 13

nicotinic receptor

Question 14

What are the 2 subtypes of nicotinic receptors?

Answer 14

Nm and Nn

Question 15

What kind of receptor is this?
location – skeletal muscle

signaling mechanism – ligand gated ion channel

each channel composed of 4 different subunits: α1 β1 δ (γ or ε)
adult – (α1)2 β1 δ ε
neonatal - (α1)2 β1 δ γ

response – muscle contraction

Answer 15

nicotinic muscle receptor

Question 16

Nm receptors increase (blank) so that you get muscle contraction.

Answer 16

sodium

Question 17

What kind of receptor is this?
location – all sympathetic and parasympathetic ganglia, adrenal medulla, CNS

signaling mechanism – ligand gated ion channel

each channel composed of different α (8 isoforms, α2- α9) and β (4 isoforms, β2- β5) subunits in various ratios

response – neuronal excitation

Answer 17

Nn Nicotinic neuroganglionic receptors

Question 18

What are the four receptor types of Nicotinic receptors?

Answer 18

muscle type, ganglion type, heteromeric type and honomeric type.
(They differ by subunit combinations)

Question 19

Where are the muscle type nictonic receptors found?

Answer 19

neuromuscular junctions

Question 20

Where are nicotinic ganglian cells found?

Answer 20

autonomic ganglia

Question 21

Where are heteromeric and homomeric type nicotinic receptors found?

Answer 21

brain

Question 22

What do all the types of nictonic receptors except for homomeric type have in common?

Answer 22

excited by increased Na and K permiability

Question 23

How many muscarinic subtypes are there?

Answer 23

5

Question 24

What receptors does this describe:

location – smooth muscle (blood vessels, airways,
eye, gut, bladder)
-endothelial cells (blood vessels)
-exocrine glands (salivary glands, sweat
glands, airways, gut)
-CNS

signaling mechanism – Gq activation of phospholipase C

response- stimulate smooth muscle contraction

      - relax blood vessels 
      - stimulate secretion

Answer 24

Muscarinic M1,M3,M5 receptors

Question 25

What is the pathway that the muscarinic receptors use?

Answer 25

PLC+ PIP2-> IP3 +DAG-> Ca2+

Question 26

How come muscarinic receptors 1,3,5 can constrict smooth muscle YET dilate blood vessesls?

Answer 26

Some blood vessels have parasympathetic innervation. In these blood vessels muscarinic receptors are there. The pathway for muscarinic receptors create NO which can diffuse from endothelial cell to vascular smooth muscle->cGMP-> inhibits contractions in the blood vessles ONLY via ENDOTHELIAL CELLS!

Question 27

Can you get ACh relexation in the vascular smooth muscle if you rub of endothelial cells?

Answer 27

no

Question 28

What receptors does this describe: Low doses of (exogenous) ACh cause systemic vasodilation and hypotension due to activation of muscarinic receptors on vascular endothelial cells. High doses of (exogenous) ACh cause systemic vasoconstriction and hypertension due to activation of muscarinic receptors on vascular smooth muscle cells.

Answer 28

M1,M3,M5 receptors

Question 29

What does this describe: location – smooth muscle (blood vessels, airways, eye, gut, bladder) endothelial cells (blood vessels) exocrine glands (salivary glands, sweat glands, airways, gut) CNS signaling mechanism – Gq activation of phospholipase C response – stimulate smooth muscle contraction relax blood vessels stimulate secretion

Answer 29

M1, M3, and M5 receptors

Question 30

Which muscarine receptors stimulate fluid secretion, gastic secretion, vesicular release of mucus and proteins (enzymes)?

Answer 30

M1,M3,M5

Question 31

What muscarine receptors does this describe? location – cardiac muscle, CNS signaling mechanism –Gi inhibition of adenylyl cyclase, Gi/o activation of K+ channels response –decreases heart rate (SA node), slows cardiac action potential propagation (AV node),decreases contractility (atria and ventricles*)

Answer 31

M2 and M4 | cardiac M2) (CNS M4

Question 32

How does M2 receptors affect the SA node of heart? (remember muscarine receptors are only parasympathetic, besides sweat glands)

Answer 32

Parasympathetic stimulation produces a negative chronotropic effect by two mechanisms - By inhibiting cAMP production, M2 receptor activation reduces the stimulatory effect that cAMP has on pacemaker and other channels. - By activating K+ channels, M2 receptor activation hyperpolarizes the membrane potential of pacemaker cells, decreasing excitability

Question 33

How does M2 receptors affect the SA node of heart? (remember muscarine receptors are only parasympathetic, besides sweat glands)

Answer 33

Parasympathetic stimulation produces a negative chronotropic effect by two mechanisms - By inhibiting cAMP production, M2 receptor activation reduces the stimulatory effect that cAMP has on pacemaker and other channels. - By activating K+ channels, M2 receptor activation hyperpolarizes the membrane potential of pacemaker cells, decreasing excitability

Question 34

How does M2 receptors affect Ventricular monocytes?

Answer 34

In the presence of sympathetic tone, parasympathetic activation can inhibit ventricular contractility.

Question 35

Compounds that mimic the responses produced by cholinergic | stimulation can be divided into two different categories:

Answer 35

Direct and Indirect

Question 36

What are the 2 categories of direct-acting drugs?

Answer 36

alkaloids and choline esters

Question 37

What are two important direct acting choline esters?

Answer 37

acetylcholine and bethanechol

Question 38

Methyl substitution on β carbon (orange) of methacholine and bethanecol reduces potency at nicotinic receptors and limits hydrolysis by (blank). The carbamic acid ester group (green) of carbachol and bethanecol limits hydrolysis by (blank)

Answer 38

cholinesterases.

Question 39

(blank) has longer half-life than ach (less susceptible to cholinesterases) and does not activated nicotonic receptors.

Answer 39

bethanechol

Question 40

Why does bethanechol have a less affect on the heart?

Answer 40

because it is works on odd muscarine receptors which arent common in the heart

Question 41

(blank) cholinomimetics work by inhibitin cholinesterase breakdown of endogenos ACh.

Answer 41

Indirect acting

Question 42

AChE contains two important sites at catalytic center, what are they?

Answer 42

Anionic site – interacts nitrogen and methyl groups of ACh | Esteratic or esteric site – serine + carboxyl residue of the acetyl group of ACh (ester linkage)

Question 43

AChE contains two important sites at catalytic center, what are they?

Answer 43

Anionic site – interacts nitrogen and methyl groups of ACh | Esteratic or esteric site – serine + carboxyl residue of the acetyl group of ACh

Question 44

What are the key steps in hydrolysis of ACh

Answer 44

Binding of ACh to anionic site Cleavage of ACh at the ester linkage releasing choline Reaction with water yielding acetic acid

Question 45

Cholinesterase inhibitors block ACh hydrolysis by:

Answer 45

Interfering with anionic site, or Interfering with esteratic site

Question 46

What are these effects of: - Low levels – increase skeletal muscle activity (fasciculations) - High levels – neuromuscular blockade - Increased ganglionic transmission - Complex cardiovascular responses - CNS effects

Answer 46

cholinesterase inhibitors

Question 47

Compounds that mimic the responses produced by cholinergic stimulation can be divided into two different categories:

Answer 47

Direct and Indirect

Question 48

What category are these a part of: - Mono- or bis-quaternary amines – edrophonium - Carbamates – neostigmine, physostigmine

Answer 48

cholinesterase inhibitors (REVERSIBLE)

Question 49

What category are these a part of: Mono- or bis-quaternary amines – edrophonium Carbamates – neostigmine, physostigmine

Answer 49

cholinesterase inhibitors

Question 50

``` What category are these a part of: Organophosphates -echothiophate – used clinically -parathion, malathion, diazinon used as insecticides -sarin, soman used as “nerve gases” ```

Answer 50

Cholinesterase inhibitors (IRREVERSIBLE)

Question 51

Can anything overcome organophospates?

Answer 51

2-PAM or pralidoxime if applied immediately, if some time passes (i.e. aging) organophosphates will be completely irreversible

Question 52

Can anything overcome organophospates?

Answer 52

2-PAM or pralidoxime if applied immediately, if some time passes, organophosphates will be completely irreversible

Question 53

What is an important direct acting choline ester?

Answer 53

bethanechol

Question 54

What is the therapeutic use of direct acting choline esters?

Answer 54

postoperative and neurogenic ileus | postoperative urinary retention

Question 55

What are the effects of direct acting choline esters(bethanechol)?

Answer 55

causes smooth muscle contraction (GI and urinary tract)

Question 56

What is the mechanism of action for direct acting choline esters?

Answer 56

muscarinic agonist – activates M1 and M3 receptors | negligible effect at nicotinic receptors

Question 57

What is an example of a direct acting alkaloid?

Answer 57

pilocarpine

Question 58

Was it the therapeutic use of direct acting alkaloids?

Answer 58

Glaucoma | Sjögren’s syndrome, xerostomia

Question 59

Was is the effect of direct acting alkaloids?

Answer 59

contracts sphincter and ciliary muscles of the eye facilitating aqueous humor outflow (glaucoma) stimulates salivary gland and tear duct secretions (Sjögren’s)

Question 60

What is the mechanism of action for direct acting alkaloids?

Answer 60

muscarinic agonist (primarily M3 receptor)

Question 61

What is an example of a direct acting nicotinic agonist?

Answer 61

Nicotine : )

Question 62

What are the therapeutic uses of direct acting nicotinic agonists?

Answer 62

medical – smoking cessation | non-medical – smoking, insecticides

Question 63

What are the effects of direct acting nicotinic agonists?

Answer 63

activates NN receptors in central nervous system activates NN receptors on postganglionic sympathetic and parasympathetic neurons activates NM receptors at the neuromuscular junction

Question 64

What is the mechanism of action for direct acting nicotinic agonists?

Answer 64

agonist at Nm and Nn receptors

Question 65

What is an example of a cholinesterase inhibitor?

Answer 65

neostigmine

Question 66

What are the therapeutic uses of cholinesterase inhibitor?

Answer 66

treatment of myasthenia gravis postoperative and neurogenic ileus postoperative and neurogenic urinary retention

Question 67

What is the mechanism of action for cholinesterase inhibitor?

Answer 67

reversible cholinesterase inhibitor

Question 68

What is the effect of cholinesterase inhibitors?

Answer 68

generalized parasympathetic stimulation

Question 69

(blank) is when you lose control of muscle contraction.

Answer 69

myasthenia

Question 70

What can cure myasthenia graves?

Answer 70

neostigmine by competitvely inhibiting the antibodies so you can get contraction

Question 71

In cholinergic toxicity from direct acting nicotinic agonists, what are the predictable symptoms?

Answer 71

acute toxicity CNS effects: convulsions, coma, respiratory arrest neuromuscular effects: respiratory paralysis cardiovascular effects (via CNS): hypertension, cardiac arrhythmias chronic toxicity CNS effects responsible for addictive properties of smoking increased incidence of peptic ulcers

Question 72

In cholinergic toxicity from direct acting nicotinic agonists, what are the predictable symptoms?

Answer 72

acute toxicity CNS effects: convulsions, coma, respiratory arrest neuromuscular effects: respiratory paralysis cardiovascular effects (via CNS): hypertension, cardiac arrhythmias chronic toxicity CNS effects responsible for addictive properties of smoking increased incidence of peptic ulcers

Question 73

What does this describe? - carbamate cholinesterase inhibitors and organophosphates are commonly found in insecticides - also found in chemical warfare agents (nerve gases) initial signs same as for muscarinic agonist intoxication CNS effects: confusion, ataxia, convulsions, coma, respiratory arrest, cardiovascular collapse Neuromuscular effects: weakness, fasciculations, paralysis Treatment: atropine, 2-PAM Prevention: pyridostigmine

Answer 73

toxicity from indirect acting compounds