There are currently five approved medications for Alzheimer's disease, four of which are called acetylcholinesterase inhibitors, or AChEIs---donepezil, rivastigmine, galantamine and tacrine. The fifth drug is the NMDA receptor antagonist, memantine. All of these medications can help in the management of Alzheimer's disease symptoms. Though beneficial, they also produce side effects, some of them serious. This is the case with tacrine, which is now only rarely used due to adverse effects on the liver.
Side Effects
A November 2008 review by David Hogan in the "Canadian Medical Association Journal" found that gastrointestinal problems are the main side effects of AChEIs. The most common is nausea, but vomiting, diarrhea and decreased appetite, especially with rivastigmine, can also occur. Other side effects include dizziness with galantamine and rivastigmine, and insomnia and cramps with donepezil. Memantine has a low side effect profile although constipation, confusion, headache and hypertension may arise. Most adverse events occur in between 8 to 23 percent of people and normally subside within the first few days of starting a drug.
Causes of Side Effects
Acetylcholinesterase is an enzyme that breaks down the chemical acetylcholine, which is reduced in some brain regions of people with Alzheimer's disease; hence symptoms being aided by AChEIs block this enzyme. Nerve cells containing acetylcholine are found in a number of brain areas so side effects such as dizziness can be due to drugs increasing acetylcholine in areas not affected by Alzheimer's disease.
As acetylcholine also has actions outside the brain, gastrointestinal symptoms are caused by AChEIs increasing acetylcholine levels in this region. Rivastigmine also inhibits another acetylcholine breakdown enzyme called butyrylcholinesterase. This is found more in the periphery, hence more gastrointestinal side effects with rivastigmine. Similarly the cramps experienced by some people using donepezil have been linked to increased acetylcholine action on muscle contraction.
Exacerbating Pre-Existing Conditions
Side effects may also be due to how Alzheimer's disease medications affect other medical problems. As AChEIs can cause gastrointestinal symptoms, people with ulcers should be monitored for increased incidence. AChEIs can cause slow heartbeat, or bradycardia, in some people, thus may not be used in those with cardiac conduction conditions. Asthma, chronic obstructive pulmonary disease and liver impairment can also be exacerbated by AChEIs. Although memantine has fewer side effects than the AChEIs, its use is cautioned in people with cardiovascular disease, seizures or renal impairment.
Interactions With Other Medications
Other drugs may interact with Alzheimer's disease medications to increase side effects. For instance, some muscle relaxants mimic acetylcholine's actions and the drug paroxetine is metabolized in the liver in a way that can increase galantamine levels. The drugs amantadine and ketamine have exacerbating effects similar to memantine.
Combating Side Effects
As many of the side effects occur only at the start of therapy and at higher doses, the American Psychiatric Association advises initiating therapy at a low dose and asking a patient to wait a few days to see if the side effects go away. To avoid the gastrointestinal side effects of rivastigmine, tablets should be taken with food, or a rivastigmine patch should be used. A change from one AChEI to another can also be made if one is causing unpleasant symptoms as these kind of meds all have slightly different side effect profiles.
References
- "American Journal of Psychiatry;" American Psychiatric Association Practice Guideline for the Treatment of Patients with Alzheimer's Disease and Other Dementias. Second Edition; APA Work Group on Alzheimer's Disease and Other Dementias; Dec 2007
- "Canadian Medical Association Journal;" Diagnosis and Treatment of Dementia: 5. Nonpharmacologic and Pharmacologic Therapy for Mild to Moderate Dementia; David Hogan et al; November 2008
- Aricept/donepezil Prescribing Information; http://www.aricept.com/PI.html
- Exelon/rivastigmine Prescribing Information; http://www.exelonpatch.com/home.jsp
- Razadyne/galantamine Prescribing Information; http://www.razadyneer.com/
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