Cholinergic Pharmacology: The Basics

Question 1

ACh Synthesis:

Answer 1

ACh is synthesized in nerve terminals by the enzyme CHOLINE ACETYLTRANSFERASE from CHOLINE and ACETYLCOENZYME A

Question 2

ACh Degradation:

Answer 2

ACh is hydrolyzed by the enzyme acetylcholinesterase into:

acetate and choline

Question 3

What are the two receptor types?

Answer 3

nicotinic and muscarinic

Question 4

Nicotinic Receptors

Answer 4

stimulate autonomic ganglia and sk. m.

these receptors are also activated by the nicotine alkaloid

Question 5

Muscarinic Receptors

Answer 5

stimulate end organ receptors

these receptors are also activated by the alkaloid muscarine

Question 6

How does normal muscle action work?

Answer 6

NM Transmission depends on the release of ACh from presynaptic neurons and activation of postsynaptic nicotinic cholinergic receptors on the motor end plate

Question 7

How do non depolarizing muscle relaxants work?

Answer 7

NM transmission is blocked by non depolarizing muscle relaxants that bind to POSTSYNAPTIC NICOTINIC cholinergic receptors

Question 8

Reversal of Nondepolarizing Muscle Relaxants:

Spontaneous Reversal

Answer 8

occurs with gradual diffusion
redistribution
metabolism
and excretion of non depolarizing muscle relaxant

Question 9

Reversal of Nondepolarizing Muscle Relaxants:

Pharmacologic Reversal

Answer 9

occurs with the admin of specific reversal agents

Reversal with acetylcholinesterase inhibitors should be monitored with a peripheral nerve stimulator

At least 1 twitch with TOF stim should be present before reversal

Question 10

What are organophosphates?

Answer 10

they are used in ophthalmology and pesticides.

they IRREVERSIBLY bind to cholinesterase inhibitors

Question 11

Side Effects of Acetylcholinesterase Inhibitors

Answer 11

in addition to increasing the availability of acetylcholine at the NMJ, inhibition of acetylcholinesterase can increase CHOLINERGIC receptor activity elsewhere leading to side effects.

Question 12

Side Effects of Acetylcholinesterase Inhibitors:

Cardiovascular

Answer 12

CV System: the predominant muscarinic effect on the heart is vagal like bradycardia that can progress to sinus arrest

Question 13

Side Effects of Acetylcholinesterase Inhibitors:

Pulmonary

Answer 13

Pulmonary Receptors: muscarinic stim can result in bronchospasm and increased respiratory secretions

Question 14

Side Effects of Acetylcholinesterase Inhibitors:

Cerebral

Answer 14

Cerebral receptors: Physostigmine is a cholinesterase inhibitor that can cross the BBB. It can diffuse activation of the EEG by stimulating muscarinic and nicotinic receptors within the CNS

Question 15

Side Effects of Acetylcholinesterase Inhibitors:

GI

Answer 15

GI Receptors:

muscarinic stim increases peristaltic activity - esophageal, gastric, and intestinal;

Glandular secretions - salivary and parietal

Periooperative bowel anastomotic leakage

Nausea and vomiting

Fecal incontinence

Question 16

Neostigmine: Mechanism of Action

Answer 16

acetylcholinesterase inhibitor

Question 17

Neostigmine: Dosage

Answer 17

up to 0.08 mg/kg in children

5 mg in adults

Question 18

Neostigmine: Onset

Answer 18

effects apparent in 5-10 mins

peak at 10 minutes and last more than 1 hour

Question 19

Neostigmine: Clinical Note

Answer 19

typically administered with glycopyrrolate to prevent bradycardia

Question 20

Neostigmine: Structure

Answer 20

carbamate moiety - binds to acetylcholinesterase

quaternary ammonium group - prevents passage across BBB

Question 21

Pyridostigmine: Mechanism of Action

Answer 21

acetylcholinesterase inhibitor

Question 22

Pyridostigmine: Dosage

Answer 22

up to 0.4 mg/kg in children

20 mg in adults

Question 23

Pyridostigmine: Onset

Answer 23

effects apparent in 10-15 mins and lasts more than 2 hours

Question 24

Pyridostigmine: Clinical Note

Answer 24

typically admin with glycopyrrolate to prevent bradycardia

Question 25

Pyridostigmine: Structure

Answer 25

carbamate moiety - binds to actylcholinesterase quaternary ammonium incorporated into PHENOL ring - prevents passage across BBB

Question 26

Edrophonium: Mechanism of Action

Answer 26

acetylcholinesterase inhibitor

Question 27

Edrophonium: Dosage

Answer 27

0.5 - 1 mg/kg

Question 28

Edrophonium: Onset

Answer 28

most rapid onset and shortest duration for class. effects apparent in 1-2 mins. higher dosages last up to 1 hour.

Question 29

Edrophonium: Clinical Note

Answer 29

typically administered with atropine to prevent bradycardia. If used with glycopyrrolate, should be given several minutes after glycol so that onset time matches

Question 30

Edrophonium: structure

Answer 30

noncovalent binding to acetylcholinesterase Quaternary ammonium group - prevents passage across BBB

Question 31

Physostigmine: Mechanism of Action

Answer 31

Acetylcholinesterase inhibitor

Question 32

Physostigmine: Dosage

Answer 32

0.01 - 0.03 mg/kg

Question 33

Physostigmine: Clinical Note

Answer 33

can be used to treat anticholinergic toxicity from scopolamine or atropine overdose also reverses some of the CNS depression from benzodiazapines and volatile anesthetics

Question 34

Physostigmine: Structure

Answer 34

carbamate moiety. lack of quaternary ammonium allows passage across the BBB

Question 35

Which cholinesterase inhibitor allows passage across the BBB?

Answer 35

Physostigmine - b/c it lacks the quaternary ammonium group

Question 36

Sugammadex: Mechanism of Action

Answer 36

hydrophobic structural interactions trap aminosteroid NMBA (rocuronium, vecuronium) within CYCLODEXTRIN cavity, terminating NMB

Question 37

Suggamadex: Dosage

Answer 37

4 - 8 mg/kg

Question 38

Suggamadex: onset

Answer 38

can reverse shallow and deep NMB within 2 mins

Question 39

Suggamadex: Clinical Note

Answer 39

b/c of concerns about hypersensitivity and allergic reactions, not yet approved by US FDA currently available in Europe

Question 40

Suggamadex: Structure

Answer 40

Modified cyclodextrin

Question 41

L-Cysteine: Mechanism of Action

Answer 41

combines with gantacurium to form less active degradation products

Question 42

L-Cysteine: Dosage

Answer 42

10-50 mg/kg

Question 43

L-Cysteine: Clinical Note

Answer 43

Still in investigative stages

Question 44

L-Cysteine: Structure

Answer 44

an endogenous amino acid

Question 45

The parasympathetic nervous system uses acetylcholine where?

Answer 45

As a PREganglionic and POSTganglionic NT

Question 46

Nicotinic receptors are blocked by_______ Muscarinic receptors are blocked by _________

Answer 46

Muscle relaxants (NMBAs) Anticholinergic drugs (ex: atropine)

Question 47

Nicotine stimulates _______ Muscarine activates _______

Answer 47

Autonomic ganglia and skeletal muscle receptors (nicotinic receptors) End organ effector cells in bronchial smooth muscle, salivary glands and SA node (Muscarinic receptors)