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Dementia and Pharmacy Intervention

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1 Dementia and Pharmacy Intervention
Melissa R. Lewis, Pharm.D. September 17, 2010

2 Objectives Define dementia and understand the requirements for diagnosis Recognize the neuropathology and neurotransmitters involved in dementia Discuss the pharmacokinetics and pharmacodynamics in the geriatric population Be able to assess a patient with or suspected to have dementia and make recommendations to optimize therapy

3 A Brief History First coined by a French physician in 1801
Dr. Philippe Pinel Alzheimer’s disease first described in 1906 Dr. Alois Alzheimer Dr. Philippe Pinel worked with a 34 year-old women who lost her memory, speech, ability to walk and use of common house hold items in over a period of just a few years- Autopsy noted brain full of fluid and significantly decreased size Alois Alzheimer worked with a 51 year-old women with memory failure, paranoia, and decrease executive functioning Autopsy of brain noted fluid, shrunk and neurofibrillary tangles and amyloid plaques. - 4 hallmark features of AD; Reference: Tam Cummings, MS, Gerontologist; (central Texas area website for geriatric information)

4 Types of Dementia Mild Cognitive Impairment (MCI)
Alzheimer’s Disease (AD) Vascular Dementia Lewy Body Dementia Frontal Lobe dementia Mixed Dementia Short definition of all types: MCI may be a transition or progress to AD; Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. Lewy type, is a type of dementia closely allied to both Alzheimers and Parkinson's Diseases. It is characterized by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons,; FLD- changes in personality/usually effect younger population; mixed when patients have contributing factors that could be characterized as more than one type of dementia.

5 Definition According to the Diagnostic and Statistical Manual of Mental Disorders-IV-TR Multiple cognitive deficits Memory impairment plus one or more: Aphasia Apraxia Agnosia Dysfunction is executive functioning Deficits must be severe enough to cause impairment in occupational and/or social functioning Aphasia- unable to understand or speak language; apraxia- inability to make purposeful movements; agnosia- inability to recognized objects; must represent a decline from a previously higher level of functioning

6 Epidemiology Dementia Prevalence Alzheimer’s Disease
Higher in women than men Static's vary depending on the source 3.0% with MCI in adult population % for ages to 16-25% over age 85 Alzheimer’s Disease 5.3 million people have AD 7th leading cause of death $172 billion dollars in annual costs 10.9 million unpaid caregivers DMS-IV; per Alzheimers Association 2010 facts and figures DSM-IV; Alzheimer’s Association 2010 facts and figures

7 Risk Factors for Dementia
Alzheimer’s Disease (AD) Age Family History ApoE E4 genetic allele History of psychiatric illness VaD- both increased age; sex; HTN, diabetes, CAD, HLP, Stroke/CVE Vascular Dementia (VaD) Age Conditions altering vasculature Smoking

8 Neuropathology in Brief
AD B-amyloid plaques Leads to neuronal death Neurofibrillary tangles Abnormal neurons die and form tangles Inflammation processes lead to neuronal death and plaque formations VaD Disruptions of blood flow to different structures in the brain responsible for cognition, executive functioning and behavior Neuropathology was initially discovered by autopsy; PET and CT used for 2 hallmark signs of fluid and decreased brain mass; but tangles and plaques are still questionable in scans and usually found in later stages. Lewy body dementia similar to AD with inclusion of lewy bodies

9 Neurochemical Disruptions
Cholinergic Systems Plaque formations damage cholinergic neurons and result in decrease in cognition and memory Glutamatergic System Plaque aggregation disrupts transmission of glutamate which results in stimulation of NMDA This can lead to excitotoxicity and neuronal death By binding to the NMDA receptor with a higher affinity than Mg2+ ions, memantine is able to inhibit the prolonged influx of Ca2+ ions, which forms the basis of neuronal excitotoxicity. The low affinity and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the physiological function of the receptor, as it can still be activated by the relatively high concentrations of glutamate released following depolarization of the presynaptic neuron

10 Morbidity and Mortality
Cognitive and behavioral symptoms are seen in earlier stages High rates of depression in patients and caregivers Late stages require extensive care with ADL Death occurs due to complications Aspiration Infection Falls and other injuries 7th leading cause of death

11 Differential Diagnosis
Delirium Sudden alterations in cognition Fluctuations throughout the day Impaired attention span Disturbances in sleep-wake cycle and psychomotor activity Maybe due to medical condition or medications Other psychiatric disorder Mood disorder Substance abuse and or withdrawal Per DSM-IV; with any psychiatric diagnosis, differential diagnoses must be addressed; delirium is commonly misdiagnosed as dementia (especially in elderly and acute hospital setting); depression and alcohol w/d can also mimic symptoms of dementia (more like a delirium)

12 Pharmacology in Geriatrics
Medication use in geriatrics 35% of all prescriptions dispensed 50% of all OTC medications Polypharmacy 4-5 medications At least 2 OTC medications regularly In 2000, estimates 106,000 deaths from medication errors Annual cost of $85 billion Fick DM, Arch Intern Med 2003. Fick et al. Arch Intern Med 2003; 163:

13 Geriatric Pharmacokinetics
Absorption Generally unaffected Distribution Decreased total body water Increased body fat Decreased serum albumin Metabolism Decreased hepatic blood flow and metabolizing enzymes Excretion Decreased renal function Absorption- Decreased bioavailability Decreased intestinal blood flow Decreased gastric emptying/motility Increased gastric pH Increase bioavailability Decreased first-pass effect = higher plasma concentrations Distribution- Decrease Vd for water soluble and increased Vd for fat soluble Increased free-fraction of protein bound medications Metabolism- usually decreased doses and increase frequency of administration Elimination- Decreased GFR Decreased renal blood flow and mass Decreased creatinine production can lead to inaccurate assumption of renal function

14 Geriatric Pharmacodynamics
Dopaminergic Decreased D2 receptors in striatum Serotonergic Decreased nerve terminals and transporters Cholinergic system Decreased choline acetyltransferase and cholinergic cells Gaba-ergic system Potential increase in response to potentiation at GABA receptors Adrenergic system Impaired baroreceptor function may result in orthostasis Receptor changes alter sensitivity, amount, binding and cellular response; Catterson ML et al Zubenko et al Harvard Rev Psychiatry 2000 Zubenko et al. Harvard Rev Psychiatry 2000

15 Prescribing in Geriatrics
Complete and thorough medication reconciliation Reduce polypharmacy Appropriate dosing and drug selection Utilizing pharmacists for consultation and effective communication/education Medication education focused on compliance and adherence Geriatric Medicine: An Evidence Based Approach - 4th Ed. (2003) Copyright© 2003 Spring-Verlag New York, Inc. All rights reserved. Geriatric Medicine: An Evidence Based Approach - 4th Ed. (2003)

16 Pharmacist Intervention
Screen for medication interactions Screen for medications that impair cognition or have anticholinergic side effects Prepared with alternate medication recommendations

17 Approach to Dementia Consult
Always look at the overall picture of your patient Environment Busy or loud unit New people with each shift change Medical conditions HPI and PMH Order/Assess pertinent labs Life-style changes Recent move to care facility Recent loss of loved one(s) Address differential diagnosis Delirium Medical condition Psychiatric disorder Substance induced Address medications known to alter cognition Beers Criteria Medications with anticholinergic properties Opioids might contribute to confusion but uncontrolled pain can also lead to delirium; Vascular disease and HIV are also possible causes of dementia Depression can display symptoms of irritability and confusion- note if pt has history of depression or current situation could also precipitate depression

18 Drug Interactions Occur when the effectiveness or toxicity of a drug is altered by the concomitant administration of another drug 3 classifications of drug interactions Pharmaceutic Physical or chemical incompatibility Pharmacodynamic Addition, synergism or antagonism of each drug’s effect Pharmacokinetic Changes in blood levels of the object drug pharmaceutic- syringe or y-site incompatibility; PD- Watch for duplicate therapies that can compound effects Sedation Disorientation or confusion Stimulant effects Orthostasis Hypoglycemia; PK- induction or inhibition of CYP450; alterations in renal clearance; protein binding interaction

19 Medications in Delirium
Many drugs are suspect in delirium or cognitive impairment cases Psychoactive meds suspect in 15-75% of cases Identified as definite cause in only 2-14% There are not many well designed studies examining drug-induced delirium The studies have conflicting results, vary in design and analysis Benzodiazepines and antipsychotics noted significant results in few studies Anticholinergics, anticonvulsants, antidepressants, antiemetics, antiparkinsonians, corticosteroids, H-2 antagonists, and NSAIDs were not significantly associated with delirium Critical review conclusions: the current evidence of an association of specific medications and delirium is rather weak. Gaudreau JD, et al. Psychosomatics 2005; 46(6): Gaudreau JD, et al. Psychosomatics 2005; 46(6):

20 Medications in Delirium
Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium. Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium.

21 Beers Criteria Based on expert consensus
Extensive literature reviews Utilization of the medications on the list Increase provider/facility cost Increase inpatient, outpatient and emergency visits Centers for Medicare and Medicaid (CMS) utilized in nursing home regulation Last updated in 2002 o The Beers criteria are based on expert consensus developed through extensive literature reviews identifying medications that may potentially inappropriate in older adults o Centers for Medicare and Medicaid (CMS) adopted the Beers Criteria in July 1999 for nursing home regulation. o Studies examining the use of medications found on the list indicate increased provider/facility costs and increased inpatient, outpatient and emergency visits. o The Beers Criteria was last update via an expert panel examining current literature and professional surveys in 2002 Fick DM, et al. Arch Intern Med 2003; 163:

22 Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163: PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

23 Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163: PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

24 Abbreviated Beers Criteria
Fick DM, et al. Arch Intern Med 2003; 163: PA-PSRS Patient Safety Advisory 2005; Vol 2(4)

25 Tips for Recommendations
Always include non-medication factors in consults if pertinent Environment - Pain control Medical condition - Daily routine Approach medication changes, discontinuations and/or additions one at a time Multiple changes that occur rapidly could exacerbate cognitive or behavioral changes Just because a medication might be found on the Beers Criteria or associated with delirium it might still be necessary Assess the current medical illness and past medical conditions prior to changing a therapy and weight the risk vs. benefit

26 Questions???

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