Cholinesterase inhibitors for dementia: patches, bradycardia and memantine add-on

How the class works and what to expect

In Alzheimer disease, loss of cholinergic neurons reduces acetylcholine. Cholinesterase inhibitors block the enzyme that breaks it down, so more acetylcholine remains at synapses. Donepezil, rivastigmine and galantamine are generally similarly effective, with modest improvements in cognition and memory in some patients. They do not stop the disease process.

Donepezil is often chosen first because it is taken once a day and is well tolerated. Rivastigmine is available as capsules, liquid and a transdermal patch, and galantamine also modulates nicotinic receptors. Treatment usually continues if function improves over several months. Set realistic expectations with families: stability or slower decline may be a meaningful outcome.

Rivastigmine patch: rotation, removal and heat

The patch is replaced every 24 hours. The previous patch must be removed before applying a new one, and hospitalisation and, rarely, death have followed application of multiple patches at once. Apply to clean, dry, hairless skin on the upper or lower back, where it is less likely to be pulled off, or the upper arm or chest if needed.

Rotate sites so the same spot is not reused within 14 days. The patch can be worn while bathing, but avoid prolonged external heat such as saunas or strong sunlight. Fold used patches and discard safely. If doses have been interrupted for more than three days, the prescriber restarts at the lowest strength, so report gaps rather than resuming the previous dose.

In care homes and hospitals, make patch checks part of routine skin and medication rounds. Record the site and time of each new patch on the chart, and check for an old patch before applying the next. People with dementia may remove patches or place them elsewhere, so a missing patch should be reported rather than assumed to have been applied.

Bradycardia, syncope and GI effects

Increased cholinergic activity has vagal effects on the heart, causing bradycardia, which matters especially in sick sinus syndrome or other conduction disorders. Check the pulse before doses as local policy requires and report a slow or irregular rate, dizziness or fainting. Falls in an older adult on this class should prompt a look at heart rate as well as environment.

Nausea, vomiting, diarrhoea, poor appetite and weight loss are common and are reduced by gradual dose increases. Prolonged vomiting can cause dehydration. Weigh regularly. Donepezil guidance asks patients to report worsening heartburn, black or tarry stools or bloody vomit, and to mention any history of ulcers. Cholinesterase inhibitors can also exaggerate succinylcholine-type muscle relaxation during anaesthesia.

Memantine as a different add-on

Memantine is not a cholinesterase inhibitor. It is an NMDA receptor antagonist that appears to improve cognition and function in moderate to severe Alzheimer disease and can be used together with a cholinesterase inhibitor. Its dose is reduced or the drug avoided in kidney impairment, so renal function is relevant.

Common memantine effects include dizziness, confusion, headache, sleepiness and constipation. When a patient is taking both drugs, attribute new symptoms carefully: bradycardia and vomiting point toward the cholinesterase inhibitor, while new dizziness or confusion after starting memantine deserves its own report. Families benefit from a written list of which tablet or patch does what.

Worked exam-style scenario

Imagine a hypothetical resident with Alzheimer disease who uses a rivastigmine patch and is found drowsy, vomiting and sweating, with a pulse of 46. On inspection there are two patches on the back. Options include applying today's patch as scheduled, giving an antiemetic, encouraging oral fluids, or removing all patches and escalating promptly.

Removing the patches and escalating is the strongest answer because multiple patches can cause cholinergic toxicity with bradycardia. Applying another patch adds to the dose. An antiemetic or fluids treat a symptom while the cause remains. The case also tests a teaching gap: caregivers need a reliable routine for removing the old patch first.

Sources and further reading

DailyMed: EXELON (rivastigmine) patch prescribing information. Patch application, 14-day site rotation, multiple-patch harm, heat exposure, retitration after interruption, GI effects, bradycardia and anaesthesia interaction.

MSD Manual Professional: Alzheimer disease. Cholinesterase inhibitor effectiveness and adverse effects, donepezil as first line, and memantine mechanism, renal dosing and combination use.

MedlinePlus: Donepezil. Fainting, slow heartbeat and GI bleeding warning symptoms, and ulcer and heart history.