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    Fighting Alzheimer's

    Today's weapons, tomorrow's targets


    Alzheimer's disease is a devastating neurodegenerative disorder that continues to afflict millions of Americans each year. But despite its prevalence, there are no medications on the market to prevent the disease or reverse the damage it causes. This leaves physicians and pharmacists struggling to find the best treatment options.

    Pharmacists now are armed with medications that can at best only slow the progression of the disease. However, new disease-modifying drugs on the horizon could change how the disease is attacked and may give pharmacists more therapeutic options.

    According to the Alzheimer's Association, an estimated 5.4 million Americans have Alzheimer's disease, and by 2030 the number of Alzheimer's patients 65 years of age or older is expected to grow to 7.7 million.

    Current treatment options

    Although there are no disease-modifying agents on the market to treat Alzheimer's disease, there are medications that seek to minimize symptoms and slow the disease's progression.

    Sean Jeffery
    Of the 5 drugs that have earned FDA approval for treating Alzheimer's disease, 4 are cholinesterase inhibitors and operate similarly. "They are all working under the hypothesis that one of the things that is affected in the brain of a dementia patient is the ability to produce certain neurotransmitters. Acetylcholine is one of those neurotransmitters that characteristically declines, and it's an important one for cell signaling. These drugs block the pathway by which acetylcholine is degraded in the brain or is broken down," said Sean Jeffery, PharmD, CGP, FASCP, a full-time faculty member at the University of Connecticut School of Pharmacy.

    Donepezil HCl (Aricept, Eisai and Pfizer), galantamine (Razadyne, Janssen Pharmaceuticals), rivastigmine (Exelon, Novartis Pharmaceuticals), and tacrine (Cognex, Shionogi Pharma) are all recommended for mild-to-moderate dementia of the Alzheimer's type and from a clinical perspective do not differ greatly, said Jeffery, who also has a practice at the VA Connecticut Healthcare System, where he serves as a pharmacist on a geriatric consult service.

    "Sometimes there are some differences in tolerability, so that's one thing that we look at," he said.

    Michael Swanoski
    Tacrine, the first Alzheimer's medication to come on the market, is no longer used regularly. "It had to be dosed multiple times a day, and there were some adverse effects associated with it that make it less desirable than the agents that followed it," said Michael Swanoski, PharmD, CGP, FASCP, assistant professor in the department of pharmacy practice and pharmaceutical sciences at the University of Minnesota.

    Rivastigmine is also distinctive because of its delivery method. In addition to an oral version of the drug, it is also available in a transdermal patch. This option may be helpful in a long-term-care setting for patients who may have difficulty eating or swallowing. Swanoski said that for some patients, the patch could also minimize nausea, a common side effect associated with cholinesterase inhibitors.

    Other side effects of cholinesterase inhibitors include loose stools, urinary frequency, incontinence, and vivid dreams.

    The final agent used to treat Alzheimer's disease is memantine (Namenda, Forest Laboratories), an N-methyl-D-aspartate (NMDA) receptor antagonist. This drug is indicated for moderate to severe dementia of the Alzheimer's type and can be used alone or in combination with cholinesterase inhibitors.

    "There's evidence to show that using the memantine together with the cholinesterase inhibitors is more effective than the cholinesterase inhibitors alone or the memantine alone, but if the patient is not tolerating the cholinesterase inhibitors, memantine is an option to be used by itself," Swanoski said.

    Memantine works by blocking glutamate action.

    Ling Li
    "It's reducing some toxicity, because sometimes it appear that, in the Alzheimer's brain, a neurotransmitter like glutamate could be too much or too active, causing toxicity," said Ling Li, DVM, PhD, professor and VFW endowed chair, department of experimental and clinical pharmacology, College of Pharmacy, University of Minnesota.

    A side effect of the medication is constipation; however, Jeffery said, pharmacists also need to be cognizant of the patient's drug regimen when administering this drug. "This is a renally eliminated drug, so you have to watch for somebody's creatinine clearance, and generally if it's less than 30, you have to make some adjustments and drugs that will alkalize the urine will decrease the clearance," he said.


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