Pharmacology · Alzheimer dementia
Donepezil, rivastigmine, and galantamine all do the same core trick: they block acetylcholinesterase so the dying cholinergic neurons in Alzheimer disease can stretch what acetylcholine is left. They are symptomatic, not disease-modifying. The board points come from telling them apart: who is once-daily, who comes as a patch and works in Parkinson dementia, and who adds a nicotinic bonus. Sort that and the question set sorts itself.
Do not memorize these three as a blur of names. Memorize one job and three personalities. The job is boosting acetylcholine. Donepezil is the simple once-daily pill. Rivastigmine is the patch that also hits butyrylcholinesterase and works in Parkinson and Lewy body dementia. Galantamine adds nicotinic receptor amplification. Know the personalities and the stem stops fooling you.
Opening challenge
A 74-year-old man with mild Alzheimer dementia cannot tolerate oral medications because of severe nausea and vomiting, and his caregiver struggles with multi-step routines. He also carries a diagnosis of Parkinson disease. Which cholinesterase inhibitor and route fit him best?
Mechanism theater
Press the stages. Acetylcholine carries memory and attention signals, but in Alzheimer the nucleus basalis neurons that make it are dying. Acetylcholinesterase normally chews acetylcholine apart in the cleft. Block that enzyme and the remaining acetylcholine lingers and works harder.
Tap a stage
Cholinergic neurons release acetylcholine into the synaptic cleft to support memory and attention. In Alzheimer disease these neurons are dying, so the acetylcholine supply is already low.
Cholinergic excess
Boosting acetylcholine everywhere means parasympathetic, SLUDGE-type effects show up as a class. The gut complains first, the heart slows, and the bladder and stomach get pushy. These are shared by all three agents.
Gut
Extra acetylcholine drives the enteric nervous systemMore acetylcholine means more gut motility and secretion: nausea, vomiting, diarrhea, cramping, and anorexia. The weight loss this causes often limits how high you can dose. into overdrive. Nausea, vomiting, diarrhea, anorexia, and weight loss are the most common and dose-limiting effects, which is why the rivastigmine patch exists.
Heart
Acetylcholine is vagotonicVagal acetylcholine slows the SA node and AV conduction, so these drugs can cause bradycardia, heart block, and syncope. Be careful in sick sinus syndrome and in patients already on beta-blockers. at the SA node, so these drugs can slow the heart, worsen conduction block, and cause fainting. Use caution in sick sinus syndrome, heart block, and patients already on rate-slowing drugs like beta-blockers.
Bladder and stomach
Parasympathetic tone squeezes the detrusorMore acetylcholine contracts the bladder detrusor (urinary urgency) and increases gastric acid secretion (caution with peptic ulcer disease). Same overdrive as the rest of the SLUDGE picture. for urinary urgency and ramps up gastric acid, so use caution in peptic ulcer disease. Same theme: parasympathetic overdrive across the body.
When a demented patient on one of these drugs faints or drops their heart rate, do not chase a zebra. That is the cholinesterase inhibitor being vagotonic at the SA node. The same drug nauseates the gut, squeezes the bladder, and stokes gastric acid. One mechanism, too much acetylcholine, explains the whole list. Know your clues.
