Section 2d Cholinergic Agonists

Question 1

Where is M2 found? How does it work?

Answer 1

Heart smooth muscle, hyperpolarization (decrease AC & increase K+ opening)

Question 2

Where is M3 found? How does it work?

Answer 2

Smooth muscle (like GI), Bladder, Exocrine gland; contraction (increase PLC and Ca)

Question 3

Where is Nm found? How does it work?

Answer 3

skeletal muscle–> End-plate depolarization AND NMJ –> skeletal muscle contraction (open Na/K channels)

Question 4

Where is Nn found? How does it work?

Answer 4

anatomic ganglia –> depolarization and firing of postganglionic neurons AND adrenal medulla –> secretion of catecholamines (opening of Na/K channels)

Question 5

What is the effect of a muscarinic agonist on M2? (Heart)

Answer 5

cardiac slowing and decrease in cardiac output, and vasodilation (NO mediated effect)

Question 6

What is the effect of muscarinic agonist on M3? (GI)

Answer 6

smooth muscle (other than vascular smooth muscle) contracts and peristaltic activity increased (digestion)

Question 7

What is the effect of muscarinic agonist on M3? (Eye)

Answer 7

contraction of ciliary muscle (effects focus), pupil contraction (miosis), and lowers intraocular pressure in acute glaucoma

Question 8

What does the NMJ consist of?

Answer 8

motor neuron, motor endplate, synaptic cleft/junctional gap

Question 9

What is found on the postsynaptic membrane in the synaptic cleft of the NMJ?

Answer 9

ACh receptors adn Acetylcholineesterases

Question 10

What help ACh release in he NMJ?

Answer 10

Ca2+ and ACh binding to presynaptic neuron (+ feedback loop)

Question 11

The extent of depolarization in nicotinic receptor end-plate depolarization is dependent upon what?

Answer 11

quantity of ACh

Question 12

What is it called when a small amount of ACh causes a slight depolarization in the end-plate?

Answer 12

miniature end-plate potential (MEPP)

Question 13

What is required for muscle contraction?

Answer 13

accumulation of a sufficient concentration of ACh at the motor end plate to depolarize beyond -55mV

Question 14

What is the major function of indirect acting cholinergic agonists?

Answer 14

Act on acetylcholinesterase

Question 15

What are direct-acting cholinergic agonists also known as

Answer 15

parasympathomimetics (choline esters & naturally occurring alkaloids)

Question 16

Which is more specific for Cholinergic receptors, parasympathomimetics or ACh (itself)?

Answer 16

the drugs

Question 17

What are the 4 major Direct acting cholinergic agonists?

Answer 17

Choline esters: Methacholine, carbachol, bethanechol

Alkaloids: Pilocarpine

Question 18

Of the Parasympathomimetics (choline esters and alkaloids) which is more like ACh and which for Muscarine?

Answer 18

Acetylcholine-like = choline esters
Muscarine-like = alkaloids

Question 19

How is strength (dose) of ACh related to cardiac effects?

Answer 19

non-specific; at low doses it decreases heart rate and BP but BP is increased with super high doses

Question 20

Of the choline ester Cholinergic agonists, which one has effects of muscarinic and nicotinic receptors?

Answer 20

Carbachol

Question 21

What choline ester Cholinergic agonist has strong muscarinic activity and acts on smooth muscle of the bladder and GI?

Answer 21

Bethanechol

Question 22

What is Bethanechol used for?

Answer 22

urinary retention, glaucoma (causes pupillary contraction)

Question 23

What Cholinergic agonist is used as a mitotic agent to treat glaucoma?

Answer 23

Carbachol

Question 24

What are symptoms of Sjogren’s syndrome (dry mouth and lack of tears) treated with?

Answer 24

Pilocarpine

Question 25

What is the drug of choice in the emergency of lowering IOP in glaucoma?

Answer 25

Pilocarpine

Question 26

What is an adverse effect of Pilocarpine?

Answer 26

CNS disturbances

Question 27

Suxamethonium chloride or succinylcholine has high affinity for what receptor?

Answer 27

nicotinic receptor - used as a surgical anesthetic (used only for short durations

Question 28

Prolonged use of succinylcholine can cause what?

Answer 28

life threatening electrolyte imbalance

Question 29

What are the adverse effects of succinylcholine?

Answer 29

cardiac arrhythmia, respiratory depression, muscle rigidity, and raised IOP

Question 30

What are the 2 types of cholinesterases? Do most drug prefer to block one over the other?

Answer 30

Acetylcholinesterase (AChE) Butyrylcholinesterase (BuChE) Both are blocked pretty equally

Question 31

Besides the clinical applications, what else are AChE inhibitors used for? (2)

Answer 31

1. insecticides | 2. chemical warfare agents (nerve gas)

Question 32

Where does AChE inhibitors bind on AChE?

Answer 32

active site

Question 33

What are the 3 chemical classes of AChE inhibtors?

Answer 33

1. Simple alcohols (Edrophonium) 2. Carbamic acid esters (Neostigmine and Physostigmine) 3. Organophosphates (Isoflurophate

Question 34

What is Mysthenia Gravis?

Answer 34

autoantibodies against nicotinic receptors --> induce nicotinic receptor internalization -->thus no sodium enters via the nicotinic receptors

Question 35

What is Lambert-Eaton Myasthenic Syndrome (LEMS)

Answer 35

autoantibodies against Ca2+ channels --> Ca2+ entry and ACh release are lessened

Question 36

Edrophonium: reversible/irreversible? Long acting/short acting? Used for? chemical type?

Answer 36

1. Reversible AChE inhibitor 2. Short acting 3. Used for the DIAGNOSIS of myasthenia gravis 4. simple alcohol

Question 37

What is the antidote to Edrophonium?

Answer 37

atropine

Question 38

What can be used as an antidote to tubocurarine?

Answer 38

Edrophonium, Neostigmine

Question 39

Physostigmine: chemical type? can it pass BBB? Uses? Adverse effects?

Answer 39

1. nitrogenous carbamic acid ester 2. can cross BBB 3. increase intestinal and bladder motility, produces miosis thus lowering IOP, treatment of anticholinergic overdose 4. bradycardia (fall in Cardiac output), paralysis of skeletal muscle <-- usually seen more with higher doses

Question 40

Neostigmine: chemical type? pass BBB? Used for? Adverse effects?

Answer 40

1. synthetic carbamic acid ester 2. does NOT pass BBB 3. used for TREATMENT of myasthenia gravis 4. salivation, decreased BP, nausea, ab pain, diarrhea, bronchospasm

Question 41

What makes irreversible anticholinesterase drugs reversible? Can in pass BBB? How does it work?

Answer 41

Pralidoxime (PAM), NO, displaces phosphate group in the inactive enzyme and when it loses the Alkyl group that is called aging

Question 42

What 2 drugs are used for chronic management of myasthenia gravis? (AChE inhibitors)

Answer 42

1. Pyidostigmine | 2. Ambenonium

Question 43

What is Demecarium used for?

Answer 43

treat chronic open-angle glaucoma

Question 44

Echothiophate: chemical type? reversible/irreversible? Antidote? Uses? Adverse effects

Answer 44

1. Organophosphate 2. Irreversible 3. atropine 4. used directly in the eye for chronic treatment of open-angle glaucoma - effect may last up to a week 5. potential cataracts, limit the use due to long duration