Cholinergic agonists And AChe Inhibitors

Question 1

What are the muscarinic agonists?

BCAP

Answer 1

Bethanechol ( Uricholine)

Cevimeline ( Evoxac)

Acetylcholine ( Michol - E)

Pilocarpine (Salagen)

Question 2

What are Organophosphates?

Answer 2

Malathion

Sarin

Question 3

What are reversible AchE inhibitors?

PEND

Answer 3

Pyridostigmine ( Mestinon)
Edrophonium ( Tensilon)
Neostigmine ( prostigmin)
Donepezil ( Aricept)

Question 4

What are Cholinesterase reactivators

Answer 4

Pralidoxime (protopam)

Question 5

What are the main drug strategies to intensify ACh neurotransmission?

Answer 5

Direct activation of ACh receptors

1. nicotinic cholinergic receptor agonists
   - increase cognition in dementia
   - Smoking cessation
2. Muscarinic cholinergic receptor agonists
   - enhance parasympathetic function to treat urinary retention, glaucoma and xerostomia

Question 6

What are the main drug strategies to intensify ACh neurotransmission.

Answer 6

(2) AchE inhibitors increase the lifespan of ACh in the synapse.

• Myasthenia gravis, dimentia
• Chemical warfare insecticides

Question 7

Nicotinic receptor facts

Answer 7

Excitatory ligand gated ion channels

Nn
Nm

Activated by nicotine

Question 8

Muscarinic receptor facts

Answer 8

Mushroom

M1- M5

Glycoprotein- Coupled Receptors

Excite or Inhibit

Question 9

Why does exogenous ACh not have widespread cholinergic activation?

Answer 9

Rapid plasma breakdown

Does not reach peripheral synapse

Does not penetrate BBB

Question 10

How does peripheral mAchR agonist affect the heart?

Answer 10

It lowers BP and Heart workload

Decreased heart rate (M2)

Decreased conduction velocity

Vasodilation ( M3)

Question 11

How does increased mAchR agonist affect the lungs

Answer 11

Respiratory tract - Bronchoconstriction

Smooth muscle

Question 12

How does increase mAchR agonism affect the bladder

Answer 12

Bladder voiding

Question 13

How does mAchR affect the GI

Answer 13

Increased GI motility and secretion

Question 14

How does maAchR agonist affect the salivary and sweat glands?

Answer 14

Stimulate secretion of salivary, nasalpharyngeal, lacrimal and sweat glands

Question 15

How does mAchR agonism affect the eyes?

Answer 15

Pupillary contraction accommodation of lens for near vision.

Question 16

How is peripheral muscarinic agonism used?

Answer 16

Stimulate salivary and ocular secretions: cevilemine and pilocarpine

Urinary retention: bethanechol

Glaucoma pilocarpine

Diagnosis of sub-clinical asthma: methacholine

Question 17

What is Sjögrens Syndrome?

Answer 17

Progressive loss of exocrine glands

Dry eyes dry mouth difficulty swallowing
And speaking

Question 18

How is Sjögren’s syndrome treated symptomatically?

Answer 18

activation of remaining M3 receptors

Question 19

What is a muscarinic agonist and how does it promote aqueous humor flow?

Answer 19

Pilocarpine:

M3 activation on ciliary muscle and pupillary constrictor leads to contraction

Beta blocker and prostaglandins reduce aqueous humor

Question 20

How do muscarinic agonist promote bladder voiding?

Answer 20

Once we are sure retention is not due to physical obstruction

Give bethanechol
M3 causes contraction in upper bladder muscle

Question 21

How can cholinergic agonist be used to diagnose asthma?

Answer 21

Bronchoprovocation with methacholine by nebulizer activates M3 receptors and cause bronchospasm in people with latent asthma.

Question 22

What are adverse effects of Muscarinic agonists?

Answer 22

Diaphoresis bronchoconstriction diarrhea cramping nausea vomiting blurred vision hypotension

Question 23

What affect doe AChe inhibition have at Cholinergic synapses?

Answer 23

Increase ACh activity at all cholinergic synapses

Question 24

Why does therapeutic AchE inhibition resemble muscarinic agonism?

Answer 24

Because all M2 and 3 receptors are activated by ACh

Question 25

What is Myasthenia Gravis

Answer 25

A skeletal muscle weakness disease. Selective or progressive destruction of motor end plate

Question 26

How is it treated

Answer 26

Using a reversible anti AChE agents that do not cross BBB Excessive muscarinic affects treated with atropine

Question 27

What is used in diagnosing MG

Answer 27

Edrophonium is used in Tensilon test

Question 28

What AchE inhibitors are used for lethality?

Answer 28

Irreversible inhibitors ``` Organophosphate synthetics (sarin- nerve gas) (Malathion- pesticide) ``` Carbamate- insecticides

Question 29

What is the cholinergic crisis produced by toxic AchE inhibition?

Answer 29

SLUDGE ``` Salvation Lacrimation urination defecation GI Distress Emesis ``` Bradycardia and hypotension

Question 30

What is an organophosphate Antidote?

Answer 30

Pralidoxime Prior to aging pralidoxime can bind to organophosphate and pull it off Does not cross BBB

Question 31

What is an antidote for all anti AchE?

Answer 31

Atropine a muscarinic agonist that penetrates CNS Main effects in the lungs To stop vasoconstriction and clear resporatory secretions.

Question 32

Which lipid-soluable anti-CHE agents and nicotonic agonists enhance cognition in Alzheimer’s?

Answer 32

``` Physostigmine Tacrine hepatotoxic Donepezil Rivastigmine Galantamine ```