Exam II: Cholinergic Agonists

Question 1

Cycle of ACh (All 6 steps)

Answer 1

1. ACh made from acetyl-CoA and choline
2. ACh stored in neurons (“quanta”)
3. Release of ACh when neurons stimulated by an action potential
4. ACh binds to ACh-R
5. AChE breaks down ACh
6. Acetyl-CoA and choline recycled

Question 2

What are the two types of cholinergic receptors?

Answer 2

Muscarinic

Nicotinic

Question 3

Are muscarinic receptors found in the sympathetic or parasympathetic nervous system…or both?

Answer 3

Parasympathetic

Question 4

Where are nicotinic receptors found ( in terms of nervous system…not specific organ )

Answer 4

Ganglionic level of both parasympathetic and sympathetic sides of ANS

Question 5

Do nicotinic receptors have inhibitory capabilities?

Answer 5

No. They only relay the efferent message sent from CNS

Question 6

If a cholinomimetic agent acts to stimulate it is an ______. In contrast, if an cholinomimetic agent acts to inhibit it is an ______.

Answer 6

Direct agonist

```
Indirect agonist
by preventing breakdown of ACh
~~~

Question 7

What are the two groups of direct-acting cholinomimetics?

Answer 7

1. Esters of Choline

2. Alkaloids

Question 8

List 4 examples of choline esters

Answer 8

1. ACh
2. Bethanechol
3. Carbachol
4. Methacholine

Question 9

List 4 examples of alkaloids

Answer 9

1. Lobeline
2. Muscarine
3. Nicotine
4. Pilocarpine

Question 10

What are the characteristics of choline esters?

Answer 10

1. Hydrophillic
   (they poorly penetrate BBB b/c of their methyl groups pulling electrons and causing a positive charge
2. Hydrolized by AChE
3. Above properties vary on chemical structure

Question 11

All alkaloids are _______ except for _____ which is a ___________.

Answer 11

Tertiary amines
Muscarine
quartenary amine

Question 12

All choline esters are ________.

Answer 12

Quarternary ammoniums

Question 13

What are the characteristics of direct acting alkaloids?

Answer 13

1. Well absorbed after oral administration
2. Lipid soluble –> allows for a larger VD
3. NOT susceptible to AChE

Question 14

What are the three types of AChE inhibitors?

Answer 14

1. Simple alcohols
2. Carbamate Esters
3. Organophosphates

Question 15

Contrast the three AChE inhibitor’s binding effects

Answer 15

Simple alcohols = bind weakly and reversibly
–> half life is very short (< 10 min)

Carbamate Esters = bind reversibly but stronger than simple alcohols
–> half life from 30 min to 6 hours

Organophosphates = covalent bonds make it nearly irreversible
–> half-life lasts hundreds of hours

Question 16

Describe the effects cholinomimetics have on the eye and what these effects facilitate.

Answer 16

1. Iris sphincter smooth muscle - contraction, causing miosis (pupil constriction)
2. Ciliary muscle –> contraction (accomodation)

These facilitate aqueous humor flow from the anterior chamber and alter the amount and focus of light reaching the retina

Question 17

What drugs are used to treat glaucoma? Describe the type of these drugs.

Answer 17

Pilocarpine (muscarine agonist)

Physostigmine (carbamate ester…AChE inhibitor)

Question 18

Describe the effects cholinomimetics have on the respiratory system.

Do we use cholinomimetics to treat respiratory conditions?

Answer 18

Cause contraction of bronchiole muscles and stimulate secretion of bronchiole glands (inc. mucous)

We do not use cholinomimetics to tx respiratory conditions

Question 19

Describe the effects cholinomimetics have on the GI system

Answer 19

Increase motility (peristalsis), increase secretion, and relax sphincter muscles

Question 20

What is a GI disorder in which you would use a cholinomimetic to tx

Answer 20

Post-operative ileus –> use neostigmine (AChE inhibitor)

Question 21

Describe the effects of cholinomimetics on the GU system

Answer 21

Detrusor muscle –> contraction

Trigone and sphincter –> relaxation

Question 22

What are cholinomimetics can be used to treat urinary retention?

Answer 22

Bethanecol (Choine ester…direct acting)

Neostigmine (Carbamate ester…indirect acting)

Question 23

What secretory glands do muscarine agonists stimulate?

Answer 23

1. Sweat glands –> diaphoresis
2. Salivary glands
3. Lacrimal glands
4. Nasopharyngeal glands –> snot

Question 24

Muscarinic receptors in the CNS are found to:

Answer 24

1. Induce tremor
2. Cause hypothermia
3. Interfer w/ nocieption (ability to sense stimuli)

Question 25

Nicotinic receptors in the CNS are found to:

Answer 25

1. Induce tremor 2. Stimulate emesis (vomitting) 3. Stimulate respiratory center

Question 26

Indirect cholinomimetics in the CNS can cause:

Answer 26

1. convusions 2. coma 3. respiratory arrest

Question 27

How are cholinomimetics used to threat Alzheimer's Disease?

Answer 27

AChE inhibitors slow progression (do not cure)

Question 28

Name 4 AChE inhibitors used to treat Alzheimer's Dz

Answer 28

1. Tacrine 2. Donepezil 3. Galatamine 4. Rivastigmine

Question 29

What drugs is used to treat smoking cessation? What does it do?

Answer 29

Varenicline A direct nicotnic agonist that decreases cravings and pleasurable effects of cigarettes

Question 30

Describe how ACh acts at the neuromuscular junction

Answer 30

1. ACh released from presynaptic neurons 2. ACh binds to nicotinic receptors on muscle fiber 3. This results in depolarization of muscle fiber 4. Causes contraction of skeletal muscle

Question 31

Contrast the effects of low, medium, and high doses of indirect cholinomimetics at the neuromuscular junction

Answer 31

LOW DOSE: prolongs effects of ACh, increasing the strength of muscle contraction MEDIUM DOSE: may cause muscles to fibrillate - muscles not effective HIGH DOSE: block depolarization causing muscle paralysis

Question 32

Myasthenia Gravis

Answer 32

An autoimmune process of antibodies targeting nicotinic receptors. These antibodies block binding of ACh to receptors

Question 33

What are some symptoms of myasthenia gravis?

Answer 33

Ptosis Difficulty speaking Weakness

Question 34

What drugs are used to treat Myasthenia Gravis?

Answer 34

AChE inhibitors

Question 35

What cholinomimetic is used to reverse neuromuscular paralysis (usually following surgery)

Answer 35

Neostigmine (an indirect acting carbamate ester)

Question 36

What do you use to treat an excessive amount of anticholinergic action in the body?

Answer 36

AChE inhibitors (physostigmine) because you want to inc. the amount of ACh at receptor sites

Question 37

Jack eats a mushroom of the genus Inocybe (containing muscarinic alkaloids). What kind of cholinomimetic toxicity does Jack have and what can be done to treat him.

Answer 37

Toxicity of Direct muscarinic agonists Tx: Atropine

Question 38

What is the fatal dose of nicotine?

Answer 38

40 mg or 1 drop of pure liquid. 2 ciagrettes has this much, but fortunately most gets destroyed by burning

Question 39

Acute nicotine toxicity can cause:

Answer 39

1. CNS stimulation (convusions, resp. arrest, coma) 2. Skeletal muscle depolarization --> leads to blockage and resp. paralysis 3. Hypertension and cardiac arrhythmias

Question 40

How do you treat acute nicotine toxicity?

Answer 40

Supportive until drug is metabolized within a few hours

Question 41

What causes cholineresterase inhibitor toxicity?

Answer 41

Organophosphates and carbamate cholineresterase inhibitors

Question 42

What symptoms are displayed when one has toxicity of cholineresterase inhibitors?

Answer 42

Muscarinic excess

Question 43

How do you treat someone with cholineresterase inhibitor toxicity?

Answer 43

1. Monitor V/S 2. Decontaminate if possible 3. Antidote w/ parenteral atropine or pralidoxime