7 Cholinergics I

Question 1

Where are the three types of muscarinic receptors found in the body?

Answer 1

M1: Postganglionic neurons of autonomic ganglia M2: Heart, primarily smooth muscle M3: Glands, smooth muscle, endothelium

Question 2

Where are the two types of nicotinic receptors found in the body?

Answer 2

N1/Nn: postganglionic neurons of autonomic ganglia (including adrenal medulla) N2/Nm: neuromuscular junction of skeletal muscles

Question 3

What are the cholinergic receptor subtypes, and what are these subtypes based on?

Answer 3

Muscarinic and nicotinic, based on selectivity for muscarine or nicotine

Question 4

What type of receptors are nicotinic receptors?

Answer 4

nicotinic receptors are ligand-gated ion channels

Question 5

What is the mechanism of action for nicotinic receptors?

Answer 5

2 ACh molecules bind to receptor and cause the Na+ channel to open, which in turn triggers an EPSP.

Question 6

What type of receptors are muscarinic receptors?

Answer 6

7 transmembrane domain receptors coupled to G proteins

Question 7

ACh and other cholinergic drugs mimic stimulation of the ______ nervous system via ______ receptors.

Answer 7

parasympathetic, muscarinic

Question 8

Why does ACh have no real therapeutic application?

Answer 8

It has limited therapeutic use because of its diffuse action and its rapid breakdown by cholinesterase.

Question 9

T or F: Synthetic choline esters and natural alkaloids are both examples of cholinergic drugs.

Answer 9

T

Question 10

Which natural alkaloids are selective for muscarinic receptors? Nicotinic receptors?

Answer 10

Muscarinic: muscarine and pilocarpine Nicotinic: nicotine and varenicline

Question 11

Name as many of the normal physiological functions of the parasympathetic nervous system as you can.

Answer 11

decrease heart rate, decrease blood pressure, activation of GI movements, emptying of bladder and rectum, activation of mucosal cells and salivary and lacrimal glands, constriction of bronchi, constriction of pupil and lens

Question 12

The rate of ACh synthesis is controlled by the rate of _____.

Answer 12

choline uptake

Question 13

Which enzyme catalyzes ACh synthesis?

Answer 13

Choline acetyltransferase (ChAT)

Question 14

Which two enzymes can catalyze the hydrolysis of ACh?

Answer 14

Acetylcholinesterase (AChE) and plasma cholinesterase (aka pseudocholinesterase and butyrylcholinesterase)

Question 15

Name the four directly-acting muscarinic receptor agonists (aka cholinomimetics).

Answer 15

acetylcholine, methacholine, carbachol, bethanechol

Question 16

Which of the cholinomimetics are susceptible to cholinesterase? Which are unaffected by cholinesterase?

Answer 16

Acetylcholine and methacholine are susceptible to cholinesterase, while carbachol and bethanechol are not

Question 17

Why are carbachol and bethanechol longer acting than the other cholinomimetics?

Answer 17

duration of action of cholinergic agonists is based primarily on susceptibility to cholinesterase; carbachol and bethanechol are not effectively hydrolyzed by cholinesterase.

Question 18

Where is acetylcholinesterase primarily found?

Answer 18

high concentrations are found at cholinergic synapses, neuromuscular junctions, and in RBCs

Question 19

Where is plasma cholinesterase primarily found?

Answer 19

plasma and liver, with limited expression in other tissues

Question 20

Which enzyme hydrolyzes ingested esters from plant sources and ACh that escapes from cholinergic synapses?

Answer 20

plasma cholinesterase

Question 21

Name the four competitive inhibitors of cholinesterases

Answer 21

edrophonium, neostigmine, pyridostigmine, physostigmine

Question 22

T or F: cholinesterase inhibitors are agonists of the parasympathetic nervous system that operate through direct stimulation.

Answer 22

F; cholinesterase inhibitors indirectly stimulate the parasympathetic nervous system by prolonging the activity of ACh in the synapse

Question 23

Name the three major types of noncompetitive cholinesterase inhibitors.

Answer 23

Organophosphate (O-P) derivatives, insecticides, and nerve gases

Question 24

O-P insecticides react first with _______, while O-P nerve gases react first with _______.

Answer 24

O-P insecticides react first with plasma cholinesterase while O-P nerve gases react first with AChE.

Question 25

Which enzyme inactivates the neuromuscular blocker succinylcholine?

Answer 25

plasma cholinesterase

Question 26

Name the three chemical categories of cholinesterase inhibitors.

Answer 26

simple alcohols with quarternary ammonium group, carbamates, and organophosphates

Question 27

Name the simple alcohol cholinesterase inhibitor

Answer 27

edrophonium

Question 28

Name the carbamate cholinesterase inhibitors

Answer 28

neostigmine, physostigmine, pyridostigmine, and carbaryl

Question 29

Which class of cholinesterase inhibitors is irreversible and longer-acting, competitive or noncompetitive?

Answer 29

noncompetitive is irreversible and long-acting, while competitive is reversible and short-acting

Question 30

Name the organophosphate cholinesterase inhibitors

Answer 30

DFP (diisopropylfluorophosphate) and echothiophate

Question 31

Explain the two step process in which ACh is hydrolyzed by AChE.

Answer 31

1) ACh bound to AChE is partially hydrolyzed to choline + acetylated AChE 2) the acetylated AChE is then hydrolyzed to acetate + AChE

Question 32

Study this.

Answer 32

Question 33

Study this too.

Answer 33

Question 34

What is the standard two-step therapy used to treat O-P intoxication?

Answer 34

treatment with 1) atropine and 2) pralidoxime (2-PAM)

Question 35

What is the function of atropine in treating O-P intoxication?

Answer 35

Antagonizing O-P actions by binding competitively to muscarinic receptors

Question 36

What does Pralidoxime do to combat O-P intoxication?

Answer 36

pralidoxime reactivates AChE that has been inhibited by O-P intoxication

Question 37

T or F: Pralidoxime combats O-P intoxication through reactivation of inhibited and aged AChE.

Answer 37

F, pralidoxime can only reactivate inhibited AChE, not aged AChE

Question 38

Why are drugs that stimulate the cholinergic system used to treat acute closed angle glaucoma?

Answer 38

cholinergic agonists reduce intraocular pressure by causing the ciliary body to contract, allowing for better drainage of aqueous humor from the anterior chamber of the eye

Question 39

What effect do cholinergic stimulants have on the GI and urinary tract? what types of conditions are they used to treat?

Answer 39

Cholinergic drugs increase the smooth muscle activity of the GI and Urinary tract, and so they are used to treat all conditions in which there is a depression (eg ileus, urinary retention, etc)

Question 40

What type of drugs are used to treat myasthenia gravis?

Answer 40

ChE inhibitors

Question 41

What are some common undesireable effects of cholinergic agonists?

Answer 41

flushing, sweating, abdominal cramps, difficulty with visual accomodation, salivation