Cholinergic Agonists

Question 1

Describe the major steps of Cholinergic transmission

Answer 1

1. ACh synthesis by ChAT (choline acetyltransferase)
2. vesicular packaging of ACh
3. release of ACh from vesicles
4. postsynaptic receptors
5. degradation by AChE (acetylcholinesterase)
6. reuptake of choline

Question 2

Describe: Vesamicol

Answer 2

inhibits packaging of ACh into the vesicle for release

Question 3

Describe: Botulinum toxin

Answer 3

blocks vesicular release into the synaptic cleft

Question 4

Describe: Hemicholinium

Answer 4

inhibits the reuptake of choline back into the cholinergic neuron

Question 5

Where are M1 receptors located?

Answer 5

neural, in the brain

Question 6

Where are M2 receptors located?

Answer 6

heart

Question 7

Where are M3 receptors located?

Answer 7

smooth muscle and glands

Question 8

Define: Cholinomimetic

Answer 8

a drug that results in the stimulation of ACh receptors, can be direct or indirect

Question 9

Define: Parasympathomimetic

Answer 9

any agent mimicking the effects of ACh

Question 10

Define: Parasympatholytic

Answer 10

any agent blocking the effects of ACh

Question 11

Define: Anticholinergic

Answer 11

a drug that blocks ACh receptors, either nicotinic or muscarinic receptors (usually blocking muscarinic receptors)

Question 12

Define: Antimuscarinic

Answer 12

a drug that blocks muscarinic receptors

Question 13

What are naturally occuring muscarinic agoinsts?

Answer 13

acetylcholine (ACh), muscarine, pilocarpine

Question 14

MOA: Acetylcholinesterase Inhibitor (AChEI)

Answer 14

competes with Ach for the active site of AChE, resulting in:
-decrease in ACh degradation
-increased ACh in the synaptic cleft
-increase ACh binding with receptor

Question 15

MOA: Non-competitive, Reversible AChE Inhibitors

Answer 15

normally AChE is briefly acetylated (inactive) by rapidly converted back into an active enzyme, but these drugs bind to AChE and form a carbamylated enzyme which is less susceptible to metabolism (stays around 30-40 minutes)

Question 16

Name the non-competitive, reversible AChE inhibitors

Answer 16

neostigmine, physostigmine

Question 17

MOA: Irreversible AChE Inhibitors

Answer 17

phosphorylated enzyme is resistant to hydrolysis so there is a very slow or no regeneration of enzyme

Question 18

Describe: 2-PAM

Answer 18

antidote for irreversible AChE inhibitors, such as organophosphates (insecticides and nerve gases)

Question 19

General Effects of Cholinergic Agonists:

Answer 19

SLUDGE
-Salivation
-Lacrimation
-Urination
-Diarrhea
-Gastric Emptying
-Emesis

Question 20

What effects do Cholinergic Agonists have on the eyes?

Answer 20

-miosis= constriction of pupils
-increased aqueous humor outflow= decreased intraocular pressure
-lacrimation= tears

Question 21

What effects do Cholinergic Agonists have on the cardiovascular system?

Answer 21

heart via M2
-decreased heart rate
-decreased conduction and contractile strength
blood vessels via M3
-little effect, since blood vessels are almost completely innervated by the SNS

Question 22

What effect do Cholinergic Agonists have on the respiratory system?

Answer 22

via M3
-contraction of bronchiolar smooth muscle and bronchoconstriction
-increased pulmonary secretions

Question 23

What effect do Cholinergic Agonists have on the genitourinary tract?

Answer 23

-contraction of detrusor muscle
-relaxation of trigone sphincter
-results in increased urination

Question 24

Why can Cholinergic Agonists used in surgery?

Answer 24

-post-surgery to stimulate GI motility and emptying of the bladder

Question 25

Why can Cholinergic Agonists be used for Myasthenia Gravis?

Answer 25

due to the nature of the disease, antibodies against nicotinic receptors on skeletal muscles, drugs such as as Pyridostigmine and Neostigmine can allow for more ACh in the synaptic cleft, but eventually all receptors will be destroyed and these drugs will no longer work

Question 26

How can Cholinergic Agonists be used for presbyopia (age-related blurry near vision)?

Answer 26

-pilocarpine eye drops contract the ciliary muscle for near vision and miosis (pupil constriction)
-be cautious driving or doing tasks in low light because eye is needed to dilate in low light, but will not be able to