Cholinergic Agonisits

Question 1

What is the rate limiting step of ACH synthesis

Answer 1

Choline uptake

Question 2

Release of Ach

Answer 2

• membrane depolarizes
• open Ca2+ channels and Ca2+ rushes in
• this causes the vesicles to move to the membrane and release Ach into the synapse

Question 3

What are the 3 fates of ACH once it is in the synapse?

Answer 3

1. Binds postsynaptic receptor
2. Metabolized by acetylcholinesterase
3. Ach binds to presynaptic nerve (same nerve that releases)

Question 4

What does Ach bind to postsynaptically

Answer 4

Nicotinic or muscarinic receptors

Question 5

How is Ach metabolized

Answer 5

By acetylcholinesterase

-breaks it into choline and esterase

Question 6

What happens to the choline once acetylcholinesterase has metabolized Ach

Answer 6

It gets recycled, it never takes in whole Ach, has to be choline

Question 7

Why does Ach have a short half life

Answer 7

Because acetylcholinesterase metabolizes it so quickly

Question 8

What happens when Ach binds to the presynaptic cleft?

Answer 8

• regulation by negative feedback
• usually an M2 receptor (GI)
• decreases CAMP, which decreases Ca2+ channels opening, which stops Ach release.

Question 9

All NT releasing neurons have to be regulated by

Answer 9

Negative feedback

Question 10

What receptors do NE bind to regulate with negative feedback

Answer 10

A2

Question 11

What receptors do dopamine have to bind to to regulate via negative feedback

Answer 11

D2

Question 12

What does an acetylcholinesterase inhibitor act like

Answer 12

Muscarinic agonist

Increases the half life of Ach

Question 13

What does Botox do to the release of Ach

Answer 13

Decreases it

Question 14

What does Botox do to a somatic muscle nerve

Answer 14

Muscle wont contract,relaxes it

Question 15

Botox and sweat glands

Answer 15

Inject into sweat glands to decrease sweat, sweat is activated by Ach

Question 16

What does spider venom do to Ach

Answer 16

Causes very increased released of Ach

Question 17

Can bind acetylcholine and the alkaloid muscarine

Answer 17

Muscarinic receptors

Question 18

What are the subclasses of muscarinic receptors

Answer 18

M1,M2,M3,M4,M5

We dont talk much anoint 4 and 5

Question 19

M1 receptors located mainly in the

Answer 19

CNS

Question 20

M2 receptors mainly located in the

Answer 20

Heart and presynaptic preganglionic nerves

Question 21

Where are M3 receptors found

Answer 21

Just about everywhere except the heart and CNS

Question 22

Properties of muscarinic receptor agonists

Answer 22

• show selectivity for muscarinic receptors
• mimic the actions of Ach but have longer 1/2 life
• parasympathetic effects + sweating (symp)

Question 23

Muscarinic receptor agonist drugs

Answer 23

• bethanechol
• carbachol
• methacholine
• pilocarpine
• cevimeline

Question 24

GI system effects of muscarinic agonists

Answer 24

-stimulates the GI tract
Increases just about everything
-may be accompanied by nausea, belching, vomiting, intestinal cramps, and defacation

Question 25

Urinary effects of muscarinic agonists

Answer 25

Increased urination - increase ureteral peristalsis - contract dertusor muscle - relax the trigone and sphincter muscle - increase max voluntary voiding pressure - decrease capacity of the bladder

Question 26

Muscarinic receptors in urinary tract

Answer 26

M3

Question 27

Muscarinic receptors in the GI Tract

Answer 27

M3

Question 28

Cardiovascular effects of a muscarinic agonist

Answer 28

M2 -decrease HR, contractility, and rate of conduction M3 -vasodilation with drugs only

Question 29

M3 receptors in the blood vessels

Answer 29

- physiologically inactive - pharmacologically useful - there are 3 receptors in BV, a1, b2, m3 - a1 is innervated and activated by epi and b2 is activated by epi from adrenal medulla - m3 has no nerve and does not get Ach from any other source. - can only be activated pharmacologically - releases NO onto smooth muscles to cause vasodilation - activated by muscarinic agonist

Question 30

Miscellaneous effects of muscarinic agonists

Answer 30

Increased secretions Bronchoconstriction Miosis and accommodation

Question 31

Why are acetylcholine and carbachol not good for the GI tract

Answer 31

They are not very selective and will also bind nicotinic receptors

Question 32

Used to stimulate the smooth muscle of the GI tract and bladder. Used for urinary retention and gastric atony

Answer 32

Bethanechol "Bowels and bladder"

Question 33

Carbachol and decreasing IOP

Answer 33

Used to decreased IOP, but it is as last choice drug for that.

Question 34

Why is carbachol's use restricted

Answer 34

Because of nicotinic effects at autonomic ganglia. Rarely used because it is not selective enough

Question 35

What is methacholine important for

Answer 35

Helps dx asthma - causes bronchoconstriction - can dx astham in subjects who do not have clinically apparent asthma (methacholine chllange test) - asthma patients more sensitive to this

Question 36

Pilocarpine and glaucoma

Answer 36

Used for open angle glaucoma and angle closure glaucoma. Not first choice. Low priority

Question 37

What are pilocarpine and cevimeline important for

Answer 37

Xerostomia - occurs after head and neck radiation tx or with sjogrens sysndrom. - stimulates salivary secretions which eases swallowing

Question 38

What is a drug you would give to someone who is having difficulty swallowing due to a dry mouth

Answer 38

Pilocarpine or cevimeline

Question 39

This is an autoimmune disease causing decreased secretion (dryness)

Answer 39

Sjogren's

Question 40

What does glaucoma treatment usually involve

Answer 40

Decreased the production or increased the drainage of aqueous humor -muscarinic agonists increase fluid drainage

Question 41

Toxicity of muscarinic agonists

Answer 41

Miosis, bradycardia, bronchoconsitrion (dont give to asthma patients), increased gastric acid production (avoid in ulcers), diarrhea, increased ruination, flushing, salivation, lacrimation, sweating

Question 42

How are muscarinic agonists given to avoid toxicity

Answer 42

Topically

Question 43

What is given to treat serious toxic reactions to muscarinic agonists

Answer 43

Atropine sulfate or epinephrine

Question 44

What kind of binding is atropine sulfate in the case of a muscarinic agonist overdose

Answer 44

Pharmacological

Question 45

What kind of binding is epinephrine in the case of a muscarinic agonist overdose

Answer 45

Physiologic Binding symp receptors while the agonist is binding parasympathetic

Question 46

Why is reversible drugs more therapeutic than nonreversible

Answer 46

Because they are less dangerous | They have temporary inhibition, binds and lets go

Question 47

This group of drugs inhibits achase

Answer 47

Acetylcholinesterase inhibitors

Question 48

How can acetylcholinesterase inhibitors be exerted

Answer 48

At either nicotinic or muscarinic receptors