Dementia and Pharmacy Intervention

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

4. Types of Dementia • Mild Cognitive Impairment (MCI) • Alzheimer’s Disease (AD) • Vascular Dementia • Lewy Body Dementia • Frontal Lobe dementia • Mixed 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

6. Epidemiology • Dementia • Prevalence • Higher in women than men • Static's vary depending on the source • 3.0% with MCI in adult population • 1.4-1.6% for ages 65-69 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 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 • 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

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

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

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

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 et al. Arch Intern Med 2003; 163: 2716-2724

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

14. 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 Geriatric Pharmacodynamics 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)

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

17. 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 Approach to Dementia Consult Always look at the overall picture of your patient

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

19. 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. Medications in Delirium Gaudreau JD, et al. Psychosomatics 2005; 46(6): 302-316

20. Medications in 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 Fick DM, et al. Arch Intern Med 2003; 163: 2716-2724

22. Abbreviated Beers Criteria

23. Abbreviated Beers Criteria

24. Abbreviated Beers Criteria

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???