A significant portion of the cognitive decline seen in older adults may be due to anticholinergic medications (i.e., muscarinic receptor antagonists) which are known to cause memory loss, confusion, and delirium. A competitive radioligand binding assay has been used in the research setting to measure the cumulative level of muscarinic receptor binding present in an individuals serum, referred to as serum anticholinergic activity (AA). Serum AA is the measure of binding of all compounds present in a persons serum (e.g., medications, metabolites, and possibly endogenous substances) to muscarinic receptors. Multiples studies have shown that even low serum AA levels are associated with impaired cognitive performance, impaired self-care capacity, and the presence of delirium in nondemented or mildly demented elderly. Serum AA has the potential to be a useful tool for clinicians. However, there are multiple items which first need to be addressed to enhance the reliability and clinical applicability of this assay.
One concern is that the muscarinic receptor binding profiles of most medications and their metabolites have never been examined. Thus, even if a clinician decides that a patient is suffering from anticholinergic-induced toxicity, he/she has little guidance on which medication(s) to adjust. To address this issue, we investigated the in vitro AA of 106 commonly used medications and estimated the relationship between dose and AA in older adults.
The change in serum AA over time in the absence of medication adjustments is not known. Another limitation is that serum AA is a peripheral measure, while the central anticholinergic effects of a medication are dependent on its distribution into the CNS. An optimal tool to predict medication-induced cognitive impairment would be one which better estimates drug distribution into the CNS. To address these issues, we conducted a pilot study investigating the utility of using centrally mediated pupillary oscillationsin conjunction with serum AA as a possible predictor of cognitive performance. Serum AA levels and ocular response were measured in a double-blind, cross-over study across an 8 hour time period following administration of placebo or the anticholinergic medication, oxybutynin.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-01202008-223707 |
| Date | 29 January 2008 |
| Creators | Chew, Marci Lyn |
| Contributors | Randall B. Smith, Samuel M. Poloyac, Bruce G. Pollock, Benoit H. Mulsant, Stuart R. Steinhauer, Robert R. Bies |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-01202008-223707/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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