Chapter 2 Peripheral nervous system drugs - cholinesterase inhibitors

Question 1

cholinesterase inhibitors

Answer 1

carbamyl ester inhibitors
* compete with acetylcholine for active system of enzyme (acetylcholinesterase)
* becomes carbamylated as it cleaves ester link (carbamyl group stops Ach from binding to active site for mins to hrs)
* upon decarbamylation – enzyme regains its ability to celave acteylcholine

organophosphorus inhibitors
* high affinity for acetylcholinestersase
* once binded — inactivates via phosphorylation
* regeneration may take a week!

• used to tx: dementia (alzheimer’s), glaucoma, mysathenia gravis

alzheimers — does not affect pathology, but may reduces sx via increasing cholinergic activity in brain
glaucoma — Ach causes constriction of sphincter muscle which surrounds iris; iris is drawn away from canal of schlemm allowing outflow of aqueous humor (glaucoma – humor production exceeds outflow casuing intraocular pressure)
myasthenia gravis
* autoimmune disease where antibodies bind to nicotinc receptors at NMJ; cholinesterase inhibitors prevent Ach degradation which inc probaility that remaning receptors will bind to acetylcholine

Question 2

Galatamine (razadyne)
Donepezil (aricept)
Rivastigmine (exelon)

agent that acts in the brain

Answer 2

• competitive, reversible cholinesterase inhibitor

clinical use – mild to moderate dementia of Alzheimer’s disease

pharmacodynamics – crosses the blood brain barrier

PO med for all

Question 3

physostigmine

agent that acts in the brain

Answer 3

• carbamyl

carbamyl ester inhibitors
* compete with acetylcholine for active system of enzyme (acetylcholinesterase)
* becomes carbamylated as it cleaves ester link (carbamyl group stops Ach from binding to active site for mins to hrs)
* upon decarbamylation – enzyme regains its ability to celave acteylcholine

• ANTIDOTE for anticholinergic overdose

pharmcokinetics — crosses the blood brain barrier

IM/IV

Question 4

Neostigmine (prostigmine)
Ambenonium (mytelase)
Pyridostigmine (mestinon)

agent that primarily act outside the brain

Answer 4

• carbamyl

carbamyl ester inhibitors
* compete with acetylcholine for active system of enzyme (acetylcholinesterase)
* becomes carbamylated as it cleaves ester link (carbamyl group stops Ach from binding to active site for mins to hrs)
* upon decarbamylation – enzyme regains its ability to celave acteylcholine

clinical uses — mysthenia gravis (autoimmune d/o in which antibodies bind to nicotinic receptors at the NMJ (more Ach available to bind to unaffected receptors)

pharmcokinetics — ambenoium has more prolonged action than the others!

PO (all)

IM/IV (neostigmine, pyridostigmine)

Question 5

Demecarium (humorsol)

topical agent used for glaucoma

Answer 5

• carbamyl

carbamyl ester inhibitors
* compete with acetylcholine for active system of enzyme (acetylcholinesterase)
* becomes carbamylated as it cleaves ester link (carbamyl group stops Ach from binding to active site for mins to hrs)
* upon decarbamylation – enzyme regains its ability to celave acteylcholine

clinical use – glaucoma

eye drops

Question 6

Echothiophate (phospholine iodide)

topical agent used for glaucoma

Answer 6

• organophosphorus

organophosphorus inhibitors
* high affinity for acetylcholinestersase
* once binded — inactivates via phosphorylation
* regeneration may take a week!

used for glaucoma, administration via eyedrops