Cholinesterase Inhibitors

Question 1

AcetylCoA pathway of synthesis and breakdown

Answer 1

Acetyl-CoA + Choline —(choline acetyltransferase)–> Acetylcholine —-(acetylcholinesterase)–> Acetate and Choline

Question 2

primary neurotransmitter for nervous system

Answer 2

ACh is the NT for ENTIRE parasympathetic NS, parts of SNS, and some CNS neurons as well

Question 3

Nicotinic Receptors

Answer 3

Autonomic Ganglia

Skeletal Muscle

Question 4

Muscarinic Receptors

Answer 4

Glands (salivary, lacrimal)
Smooth muscle (bronchi, GI, bladder, blood vessels)
Cardiac (SA and AV node)

Question 5

Ciliary ganglion

Answer 5

Innervates eye

-> contraction or iris and ciliary muscle

Question 6

Submandibular ganglion

Answer 6

Innervates salivary glands

-> secretion

Question 7

Vagus Nerve

Answer 7

Innervates:

• Heart: lowers HR, conduction, contraction
• Lungs: bronchoconstriction
• Pancreas: increased insulin secretion

Question 8

Pelvic Nerve Ganglion

Answer 8

Innervates:

• Intestine: increase tone and motility
• Bladder: sphincter relaxation and detrusor contraction

Question 9

Cholinesterase Inhibitor MOA

Answer 9

indirectly increases amount of ACh available to compete with non-depolarizing blockers
- inactivates AChE by REVERSIBLY binding enzyme

Question 10

CV Effects of cholinesterase inhibitors

Answer 10

more ACh binding, stimulates muscarinics => bradycardia to asystole (inhibiting the inhibition)

Question 11

Resp Effects of cholinesterase inhibitors

Answer 11

stimulates muscarinic => bronchoconstriction and increased secretions

Question 12

CNS Effects of cholinesterase inhibitors

Answer 12

some can cross BBB (physiostigmine) and cause confusion, increased EEG activity

Question 13

GI Effects of cholinesterase inhibitors

Answer 13

increased muscarinic => increased peristalsis and secretions and increased PONV

Question 14

Clearance of cholinesterase inhibitors

Answer 14

hepatic and renal clearance

Question 15

Neostigmine

Answer 15

lipid insoluble, peaks at 10 minutes
- crosses placenta = potential for fetal bradycardia
DOSE: 0.08 mg/kg (max of 5 mg)
- use with glycopyrolate

Question 16

Pyridostigmine

Answer 16

lipid insoluble, peaks around 30 minutes, lasts 2 hrs
- 20% as potent as neostigmine
DOSE: 0.25 mg/kg

Question 17

Edrophonium

Answer 17

lipid insoluble, lacks carbamate group
- 10% as potent as neostigmine
RAPID onset of 1-2 minutes with short duration
DOSE: 0.5-1 mg/kg

Question 18

Physostigmine

Answer 18

lipid soluble, no quaternary group (Crosses BBB)
- due to ability to cross BBB, it limits its usefulness
- also must use atropine with it
DOSE: 0.01-0.03 mg/kg
VERY good at treating CNS anticholinergic toxicity

Question 19

Sugammadex

Answer 19

Modified gamma-cyclodextrin
3-D structure resembles a hollow cone
- hydrophobic cavity and hydrophilic exterior
= forms bond with drug
Eliminated unchanged in the kidneys
DOSE: 2-16 mg/kg depending on depth of blockade
- AVOID IN RENAL FAILURE