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Alzheimer's disease is the most common cause of dementia in our older Americans. The disease is named after the psychiatrist and neuropathologist Dr. Alois Alzheimer. He discovered unique changes in the brain of a patient with severe dementia who had died – deposits of amyloid plaques and neurofibrillary tangles. Today the presence of these plaques and tangles is considered characteristic of Alzheimer’s disease. The brain shrinks due to loss of brain cells and there is decreased transmission of the chemical messages in the brain (neurotransmission).
Currently, medicine cannot remove the plaques and tangles, and we cannot replace the lost tissue in the brain. All of the prescription drugs on the market for Alzheimer’s disease are aimed at improving neurotransmission.
Tacrine has several proposed mechanisms of action, but primarily it strongly inhibits the enzyme acetylcholinesterase. We want to inhibit acetylcholinesterase because it breaks down acetylcholine, which is a neurotransmitter that has several purposes, including helping with memory. Tacrine is referred to as a cholinergic agent, because of its involvement with acetylcholine.
Tacrine was initially developed in Australia as a possible antibiotic during World War II. The drug was later studied for its ability to reverse toxicity in patients who took too much of an anticholinergic substance. Researchers began to make connections between Alzheimer’s disease and lack of acetylcholine in the brain, and work began to test tacrine’s effects in senile dementia and later for the dementia we now know as Alzheimer’s disease. Eventually, there was enough evidence for the US Food and Drug Administration to approve tacrine for the treatment of Alzheimer’s disease.
The effectiveness of tacrine was never great, but it slowed the deterioration of cognitive function and improved patients' overall clinical appearance…and patients were staying out of nursing homes longer.
The common side effects of tacrine were nausea, vomiting, diarrhea, headache, and dizziness. Unfortunately, about a third of people on tacrine developed liver damage. Frequent blood tests were required to assess liver function. In some cases the drug had to be stopped. When detected early, the liver damage was reversible. Eventually, other drugs were developed with similar effectiveness but without the liver damage, and tacrine fell out of favor. As a result, the manufacturer stopped making tacrine, and the drug was discontinued in 2013.
The cholinesterase inhibitors currently approved for use in Alzheimer’s disease are donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). Overdoses with these cholinesterase inhibitors are uncommon. The worry is that a "cholinergic crisis" might occur because there would be too much acetylcholine and too much cholinergic stimulation. The symptoms of a cholinergic crisis include severe nausea and vomiting, salivation, sweating, slow heart rate, low blood pressure, collapse, convulsions, and muscle weakness.
If you think someone might have taken too much tacrine, immediately call Poison Control at 1-800-222-1222 or check the webPOISONCONTROL® online tool for help. Whether you call or log on, expert assistance is available 24 hours a day.
Pela Soto, PharmD, BSHS, BS
Certified Specialist in Poison Information
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