Cholinergic

Question 1

MOA of Pilocarpine?

Answer 1

Contract sphincter muscles of iris, causing miosis and freeing entrance to Schlemm’ canal
Enhance tone of trabecular meshwork
Contract ciliary muscles of eye accommodating for near vision
Promote salivation

Question 2

Main use of Pilocarpine?

Answer 2

Glaucoma - both narrow and wide angle
Xerostomia

Question 3

MOA of Bethanechol?

Answer 3

GU - Raise detrusor tone and lower outlet resistance of internal sphincter
GI - Raise motility and secretion

Question 4

Use of Bethanechol?

Answer 4

Treat gastric atony and vagotomy - for PUD Mx
Treat ARU in absence of obstruction

Question 5

ADR of Nicotine in cholinergic?

Answer 5

Dependence aka addiction
For low dose - High HR, BP, RR
Higher dose can cause bradycardia, Nm blockade and medullary depression

Question 6

Mechanism of Nicotine in cholinergic? (pls refer to lect slides for explanation)

Answer 6

For Nm agonist:
Skeletal muscle contraction, fasciculations, spasms
High dose depolarizing blockade.

For neuronal agonist:
Adrenaline release
High HR
Peripheral vasoconstriction
High GI motility, GI secretions
High RR
N/V

Question 7

MOA and use of Varenicline?

Answer 7

Partial nicotinic agonist - supports smoking cessation

Question 8

Name the direct cholinergic agents and corresponding target receptors

Answer 8

Pilocarpine - M3
Bethanechol - Muscarinic, mostly M3
Nicotine - Nicotinic
Varenicline - Nicotinic

Question 9

Name the indirect cholinergics - Cholinesterase inhibitors

Answer 9

Physostigmine
Donepizil
Neostigmine
Sarin, Soman, Tabun
Parathion, Malathion

Question 10

Use of Physostigmine?

Answer 10

Antidote for atropine poisoningA

Question 11

ADR of Physostigmine?

Answer 11

Abdominal cramps
Miosis
Hypotension
Bradycardia

Question 12

Use of Donepizil?

Answer 12

Used for alzheimer’s - produce modest cognitive improvement

Question 13

MOA of Neostigmine?

Answer 13

Carbamate inhibitor of AchEsterase
Very resistant to hydration
M3 agonist - contracts GI and GU smooth muscle. Sphincter tone falls and secretions rise

Question 14

Use of Neostigmine?

Answer 14

Reverse non-polarizing Nm blockade
Treat Myasthenia Gravis
Raise GI motility on post-op or neurogenic ileus
Treat urinary retention secondary to bladder atony

Question 15

MOA of Sarin, Soman, Tabun?

Answer 15

1. Absorbed rapidly through skin, GI and lungs
2. Organophosphate nerve gas agent
3. Potent suicide inhibitor of AChE
4. Enzyme formed very resistant to hydration
5. Increase Ach at Nm junctions and neuronal synapses

Question 16

Symptoms of Organophosphate poisoning - cholinergic crisis?

Answer 16

Salivation
Lacrimation
Urination
Defecation

Question 17

Signs of acute poisoning with nerve agents?

Answer 17

Acute poisoning:
1. CNS - coma, respiratory depression, seizures, nausea, vomiting
2. Autonomic Muscarinic - bradycardia, diarrhoea, blurring of vision
3. Somatic nicotinic - muscle twitching, fasciculaton, weakness, flaccid paralysis

Organophosphate poisoning (cholinergic crisis):
1. Salivation
2. Lacrimation
3. Urination
4. Defecation

Question 18

Use of Parathion / Malathion?

Answer 18

Insecticides

Question 19

What is the antidote to nerve gas poisoning?

Answer 19

Pralidoxime - Cholinesterase regenerator
Atropine - mACh receptor blocker

Question 20

Principles of antidote to nerve gas poisoning?

Answer 20

Pralidoxime must be given within hours before “ageing” (further chemical changes making inhibition irreversible) occurs

Question 21

ADR of cholinergic agents?

Answer 21

1. Diarrhoea
2. Diaphoresis
3. Miosis
4. Nausea
5. Urinary ugency

Question 22

In what conditions are all cholinergics contraindicated?

Answer 22

Asthma
PUD