10.4 Alzheimer’s Drugs

Alzheimer's Disease Pharmacotherapy

Alzheimer's disease involves a progressive loss of neurons, particularly those that rely on acetylcholine for memory and learning. Medications can't cure or reverse the disease, but they can slow cognitive decline and help patients maintain daily functioning for longer. The two main drug classes used are cholinesterase inhibitors and the NMDA receptor antagonist memantine, each targeting a different neurotransmitter system.

Pathophysiology and Drug Targets

Alzheimer's disease is characterized by the buildup of amyloid-beta plaques between neurons and neurofibrillary tangles made of abnormal tau protein inside neurons. These deposits damage and destroy brain cells over time, especially in areas responsible for memory and cognition.

Two key neurotransmitter problems result from this neurodegeneration:

• Acetylcholine (ACh) deficit: Neurons that produce ACh are among the first destroyed. Since ACh is critical for memory and learning, this deficit drives much of the cognitive decline.
• Glutamate excess: Damaged neurons release too much glutamate, which overstimulates NMDA receptors. This leads to calcium influx and further neuron death, a process called excitotoxicity.

Alzheimer's drugs target these two imbalances. They don't stop plaque formation or reverse damage, but they compensate for the neurotransmitter disruptions that worsen symptoms.

Mechanisms of Alzheimer's Drugs

Cholinesterase Inhibitors (donepezil, rivastigmine, galantamine)

These drugs block acetylcholinesterase, the enzyme that normally breaks down ACh in the synapse. By slowing ACh breakdown, more of it stays available to stimulate receptors, which improves memory, cognition, and the ability to perform daily activities. Think of it this way: the brain is producing less ACh, so these drugs make whatever ACh is produced last longer.

• Donepezil is the most commonly prescribed; it's taken once daily and is approved for all stages of Alzheimer's.
• Rivastigmine is available as an oral capsule and a transdermal patch (the patch can reduce GI side effects).
• Galantamine also modulates nicotinic receptors, which may provide an additional boost to ACh signaling.

NMDA Receptor Antagonist (memantine)

Memantine works on a completely different system. It blocks NMDA glutamate receptors, preventing the excessive calcium influx caused by too much glutamate. This protects neurons from excitotoxicity while still allowing normal glutamate signaling needed for learning. Memantine is approved for moderate to severe Alzheimer's and is often combined with a cholinesterase inhibitor (commonly donepezil + memantine).

Indications and Effects of Alzheimer's Medications

Indications by disease stage:

• Mild to moderate: Cholinesterase inhibitors (donepezil, rivastigmine, galantamine)
• Moderate to severe: Memantine alone, or memantine combined with a cholinesterase inhibitor
• Donepezil is the exception among cholinesterase inhibitors: it's approved across all stages (mild, moderate, and severe)

Side Effects:

Cholinesterase inhibitors increase ACh throughout the body, not just the brain. This means side effects reflect cholinergic stimulation:

• GI effects (most common): nausea, vomiting, diarrhea, decreased appetite, weight loss
• Cardiovascular: bradycardia, syncope (ACh slows heart rate via the vagus nerve)
• CNS: dizziness, headache, insomnia

Memantine side effects are generally milder:

• Dizziness, confusion, headache, constipation, and hypertension

Drug Interactions:

• Cholinesterase inhibitors + anticholinergics = the drugs work against each other (anticholinergics block ACh, cholinesterase inhibitors increase it). This combination reduces the effectiveness of both.
• Cholinesterase inhibitors + beta-blockers = additive risk of bradycardia, since both slow heart rate.
• Memantine clearance depends on urine pH. Drugs that alkalinize urine (e.g., sodium bicarbonate) decrease memantine elimination, raising drug levels and toxicity risk. Carbonic anhydrase inhibitors (e.g., acetazolamide) can also alkalinize urine and have a similar effect.

Nursing Considerations for Alzheimer's Drugs

• Assess cognitive function at baseline and regularly using standardized tools (e.g., MMSE or MoCA). Document behavior, memory, and ability to perform activities of daily living (ADLs) so you can track whether the medication is helping.
• Monitor heart rate in patients on cholinesterase inhibitors. Report bradycardia (HR below 60) or signs of syncope promptly, especially if the patient is also on a beta-blocker.
• Give cholinesterase inhibitors with food to reduce nausea and vomiting. For rivastigmine patches, rotate application sites and ensure the old patch is removed before applying a new one.
• Titrate doses slowly. These medications are started at low doses and increased gradually over weeks. Rapid dose increases worsen GI and cardiovascular side effects.
• Monitor renal function for patients on memantine. The drug is primarily cleared by the kidneys, so dose adjustments are needed if creatinine clearance is reduced.
• Review the medication list for anticholinergic drugs (diphenhydramine, oxybutynin, certain antipsychotics). These directly counteract cholinesterase inhibitors and are a common source of reduced drug effectiveness.

Patient and Caregiver Education

• Take the medication at the same time every day. Consistency matters for maintaining steady drug levels. If a dose is missed, take it as soon as remembered, but don't double up.
• Take cholinesterase inhibitors with food (except donepezil, which can be taken with or without food). This significantly reduces nausea.
• Expect GI side effects early on, especially during dose increases. Nausea and diarrhea often improve after a few weeks. Contact the provider if vomiting is persistent or weight loss becomes significant.
• Report dizziness, fainting, or a slow pulse right away, as these may indicate bradycardia.
• These drugs do not cure Alzheimer's. They slow symptom progression, and the benefit may be subtle. Families should understand that "staying the same" can actually mean the drug is working.
• Encourage cognitive stimulation (puzzles, reading, social interaction, familiar routines) alongside medication. A structured daily routine helps reduce confusion and agitation.
• Connect caregivers with support resources. Alzheimer's caregiving is demanding. Refer families to the Alzheimer's Association, local support groups, and respite care services. Caregiver burnout directly affects patient outcomes.