S3 Cholinergic Drugs & Muscarinic/Nicotinic Receptors

Question 1

Acetylcholine

Answer 1

Choline ester drug

Activity at BOTH muscarinic and nicotinic receptors

Question 2

Pilocarpine

Answer 2

Muscarinic AChR agonist only
Alkaloid drug
Uses (optical)
1. Glaucoma 
a. Promotes drainage of aqueous humor 
2. Dry eye = stim. lacrimation

Question 3

Carbamylcholine

Answer 3

Choline ester drug

Activity at BOTH muscarinic and nicotinic receptors

Question 4

Bethanechol

Answer 4

Muscarinic AChR agonist only
Choline ester drug
Target = smooth muscle
Effects
1. Stimulates urinary bladder motility
2. Stimulates GI motility

Question 5

Edrophonium

Answer 5

AChE inhibitor
Reversible 
Quaternary ammonium compound 
Short duration (few minutes)
Diagnose/treat myasthenia gravis

Question 6

Pyridostigmine

Answer 6

AChE inhibitor
Reversible
Carbamate (insecticide)
Intermediate duration (15-30 min)
Diagnose/treat myasthenia gravis
Similar to Neostigmine

Question 7

Neostigmine

Answer 7

AChE inhibitor
Reversible
Carbamate
Intermediate duration (15-30 min)
Diagnose/treat myasthenia gravis
Similar to Pyridostigmine

Question 8

Organophosphates

Answer 8

AChE inhibitor
Irreversible 
Insecticides
Long duration (days)
Lipid soluble = dangerous!

Question 9

Acetylcholine (as drug)

Answer 9

Muscarinic AChR agonist at low doses
Also binds nicotinic AChRs at high doses
High doses = loss of specificity 
Effects
1. Low dose = dec. BP &dec. HR
2 High dose = inc. BP & inc. HR

Question 10

Atropine

Answer 10

Muscarinic AChR antagonist
Vasorelaxation
Similar to Scopolamine

Question 11

Carbachol

Answer 11

Muscarinic AChR agonist only
Target = smooth muscle
Effect = stimulate rumen or colonic motility
Can be dangerous!

Question 12

Scopolamine

Answer 12

Muscarinic AChR antagonist 
Optical use
Effects = smooth muscle paralysis
1. Mydraisis (pupil dilation)
2. Cycloplegia (paralysis; lens cannot focus)
Similar to atropine

Question 13

Atropa belladonna (Deadly nightshade)

Answer 13

Muscarinic AChR antagonist
Dilates pupils = mydriasis
Fixes lens = cycloplegia
Similar to atropine & scopolamine

Question 14

Trimethaphan

Answer 14

Ganglionic blocker
Nicotinic (Nn) AChR
Blocks both parasympathetic & sympathetic
No effect on skeletal muscle
Many side effects- not routinely used

Question 15

Pancuronium

Answer 15

Skeletal muscle relaxant
Nicotinic (Nm) AChR competitive antagonist
Curariform blocker = GOOD
Non-depolarizing
Acts as a neuromuscular blocker

Question 16

Succinylcholine

Answer 16

Skeletal muscle relaxant
Nicotinic AChR depolarizing agonist
Causes desensitization of the receptor
Persistent 
No reversing agents but short acting

Question 17

Nicotine (toxicology)

Answer 17

Ganglionic stimulant –> desensitization
Nicotinic AChR agonist
Skeletal muscle relaxant
Death from respiratory paralysis

Question 18

Acetylcholine (high dose)

Answer 18

Nicotinic AChR agonist
Loses specificity at high concentrations
This occurs with cholinesterase inhibitor as well

Question 19

Levamisole

Answer 19

Nicotinic AChR antagonist
Depolarizing neuromuscular blocker
Causes muscle paralysis in nematodes

Question 20

Vecuronium

Answer 20

Skeletal muscle relaxant
Nicotinic AChR competative antagonist
Curariform blocker = BETTER

Question 21

Atracurium

Answer 21

Skeletal muscle relaxant
Nicotinic AChR competative antagonist
Curariform blocker = BEST
Spontaneously decomposed in plasma = Hoffmann elimination

Question 22

Gammamine

Answer 22

Skeletal muscle relaxant

Nicotinic AChR competative antagonist

Question 23

D-Turbocurarine

Answer 23

Skeletal muscle relaxant
Nicotinic AChR competative antagonist
Dart arrow poison

Question 24

Cholinergic drugs bind what receptors?

Answer 24

Muscarinic receptors

Nicotinic receptors

Question 25

Muscarinic receptor mechanism & effects

Answer 25

Sensitive to low concentrations of ACh G-protein coupled Blocked by atropine ``` Effects 1. Smooth muscle contraction 2. Increased exocrine secretion 3. Action at cardiac nodes --> decrease HR 4. Vasodilation from NO release (low doses) ```

Question 26

Nicotinic receptor mechanism & effects

Answer 26

``` Require high concentrations of ACh Multi-subunit cation channel Blocked by Nn receptors = Trimethaphan (ganglia) Nm receptors = Pancuronium (sk. muscle) ``` Effects 1. Skeletal muscle contraction 2. Ganglionic transmission

Question 27

Ach inhibitors

Answer 27

Indirect acting drugs Raise levels of ACh by inhibiting breakdown More ACh is available to bind receptors

Question 28

Muscarinic receptors and locations

Answer 28

``` M1 a. Peripheral neurons b. CNS neurons M2 a. Heart b. Neurons c. Smooth muscle M3 a. Exocrine glands b. Blood vessels c. Eye M4 a. CNS neurons M5 a. CNS neurons ``` ``` Odd = coupled to calcium Even = coupled to decrease in cAMP ```

Question 29

SLUD sydrome

Answer 29

``` Results from AChE inhibitors overdose = Increased ACh concentrations 1. Salivation 2. Lacrimation 3. Urination 4. Defeccation Can lead to cardiac and respiratory arrest ```

Question 30

Skeletal muscle relaxants

Answer 30

``` Nicotinic competitive antagonists Pancuronium = Good Vecuronium = Better Atracurium = Best Levamisole Gammamine D-Turbocurarine ``` Desensitizing agonists Succinylcholine Nicotine