Marci L Chew

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Are you Marci L Chew?

Claim your profile

Publications (6)28.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
    Journal of the American Geriatrics Society 07/2008; 56(7):1333-41. DOI:10.1111/j.1532-5415.2008.01737.x · 4.57 Impact Factor
  • Source
    Kristin L Bigos · Marci L Chew · Robert R Bies ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Safe, effective drug therapy in older adults requires an understanding of drug disposition and response in this population. Evidence suggests that physiologic changes during aging, including hepatic or renal function changes, contribute to pharmacokinetic differences. A major issue surrounding the study of older adults relates to the ability to study a large number of people in a minimally invasive way. Population pharmacokinetics provides a potential means of addressing this issue and a tool to evaluate drug exposure's magnitude and consistency. This article highlights examples of pharmacokinetic studies in psychiatry, in particular those conducted in older adults. It also reviews new drugs approved for treatment in psychiatry or neurology, many of which were developed as novel formulations (eg, extended-release transdermal film) with improved pharmacokinetic profiles or developed with regard to the actions of a specific enantiomer or metabolite.
    Current Psychiatry Reports 03/2008; 10(1):30-6. DOI:10.1007/s11920-008-0007-4 · 3.24 Impact Factor
  • Source
    Marci Lyn Chew ·
    [Show abstract] [Hide abstract]
    ABSTRACT: 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 individual's serum, referred to as serum anticholinergic activity (AA). Serum AA is the measure of binding of all compounds present in a person's 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.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic. We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated. Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied. Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.
    Schizophrenia Research 01/2007; 88(1-3):63-72. DOI:10.1016/j.schres.2006.07.011 · 3.92 Impact Factor
  • Marci L Chew · Benoit H Mulsant · Bruce G Pollock ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The authors investigated the association between serum anticholinergic activity (SAA) and cognitive performance in a group of patients with moderate-to-severe dementia. SAA and cognitive performance were assessed in 26 patients admitted to a geropsychiatric unit for the treatment of behavioral disturbances associated with dementia. SAA was measured by radioreceptor competitive binding assay. Cognition was tested with the Mini-Mental State Exam and the Severe Impairment Battery. Higher SAA was associated with lower cognitive performance. This study extends to patients with moderate-to-severe dementia the finding that higher SAA is associated with lower cognitive performance.
    American Journal of Geriatric Psychiatry 07/2005; 13(6):535-8. DOI:10.1176/appi.ajgp.13.6.535 · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia. Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days. Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups. Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients.
    American Journal of Psychiatry 04/2002; 159(3):460-5. DOI:10.1176/appi.ajp.159.3.460 · 12.30 Impact Factor