Dementia and Pharmacy Intervention

Melissa R. Lewis, Pharm.D.

September 17, 2010

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

A Brief History

• First coined by a French physician in 1801 Dr. Philippe Pinel

• Alzheimer’s disease first described in 1906 Dr. Alois Alzheimer

Types of Dementia

• Mild Cognitive Impairment (MCI)

• Alzheimer’s Disease (AD)

• Vascular Dementia

• Lewy Body Dementia

• Frontal Lobe dementia

• Mixed Dementia

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

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

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

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

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

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

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

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

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

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

Zubenko et al. Harvard Rev Psychiatry 2000

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)

Pharmacist Intervention

• Screen for medication interactions

• Screen for medications that impair cognition or have anticholinergic side effects

• Prepared with alternate medication recommendations

Approach to Dementia Consult

• 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

Always look at the overall picture of your patient

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

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): 302-316

Medications in DeliriumMedication Class Medication

Lorazepam Diazepam Clonazepam Alprazolam Triazolam

Benzodiazepines

Clorazepate

Fentanyl * Meperidine *

Opioids

Morphine * Corticosteroids

Prednisone

Diclofenac Ibuprofen Sulindac Indomethacin Salicylic acid

NSAIDs

Ketoprofen

Clozapine * Fluphenazine Haloperidol Loxapine Olanzapine Perphenazine Quetiapine Risperidone Thioridazine

Antipsychotics

Ziprasidone

Amiodarone Lidocaine Quinidine

Antiarrhythmics

Tocainide Antiasthmatics

Theophylline

Phenytoin Acetazolamide Lamotrigine Pregabalin

Anticonvulsants

Valproic Acid*

Medication Class Medication Amitriptyline Desipramine Doxepin Imipramine Protriptyline Mirtazapine Fluoxetine Paroxetine

Antidepressants

Sertraline

Amantadine Levodpa

Dopaminergic Agents

Bromocriptine

Enalapril Captopril Lisinopril Reserpine Clonidine Methyldopa Nifedipine Verapamil Atenolol Metoprolol

Antihypertensives

Propranolol

Atropine Benztropine Scopolamine

Anticholinergics

Tolterodine

Tobramycin Bactrim

Antimicrobials

Linezolid

Digoxin Alcohol withdrawl

Other Agents

Lithium * * Documented incidence from clinical trials

Medications that have anticholinergic effects which can be associated with cognitive impairment

Borovick and F

uller. Drug-Induced D

iseases: Prevention, D

etection, and Managem

ent: 2

nd ed. AS

HP

2010; Chapter 15: D

elirium.

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

Abbreviated Beers Criteria

Drug Concern Severity Rating Propoxyphene and combinations Demonstrates analgesic effects similar to

acetaminophen with adverse effects of narcotics

Low

Indomethacin Produces most CNS effects of the NSAID class

High

Pentazocine Narcotic with several CNS effects: confusion and hallucinations

High

Trimethobenzamide Poor antiemetic effects; potential for EPS

High

Muscles relaxants and antispasmodics

Poorly tolerated in elderly; anticholinergic effects; increase fall risk

High

Flurazepam Extremely long half-life cause prolonged side effects of sedation and falls

High

Amitriptyline Potent anticholinergic; sedating High Doxepine Potent anticholinergic; sedating Meprobamate Highly addictive anxiolytic High Specific dosing of benzodiazepines

Lorazepam > 3 mg Oxazepam > 60 mg Alprazolam > 2 mg Temazepam > 15 mg Triazolam > 0.25 mg

Doses ranging higher than those suggested demonstrate little benefit with increased side effects compared to smaller doses

High

Long-acting benzodiazepines Chlordiazepoxide Diazepam Quazepam Halazepam Chlorazepate

Long half-life produces prolonged sedation and increased risk for falls

High

Abbreviated Beers Criteria

Disopyramide Particular antiarrhythmic may induce heart failure in elderly; also anticholinergic effects

High

Digoxin Closely monitor renal clearance and levels to prevent toxicity

Low

Short-acting dipyridamole Potential for orthostatic hypotenstion; long-acting formulation only in those with prosthetic heart valves

Low

Methyldopa Bradycardia; may potentiate depression High Reserpine > 0.25 mg May induce depression, impotence,

sedation, orthostatic hypotension Low

Chlorpropamide Long half-life may prolong hypoglycemia

High

GI antispasmodics Dicyclomine Hyoscyamine Belladonna alkaloids Clidinium-

chlordiazapoxide

Increased anticholinergic effects; efficacy uncertain

High

Anticholinergics/Antihistamines Chlorpheniarmine Diphenhydramine Hydroxyzine Cyproheptadine Promethazine

Potent anticholinergic High

Diphenhydramine Confusion and sedation; use lowest possible dose in allergic reactions

High

Ferrous Sulfate > 325 mg/day High doses not dramatically absorbed; constipation greatly increased

Low

Barbiturates (except Phenobarbital)

Highly addictive; harmful side effects High

Abbreviated Beers Criteria

Meperidine Advantage over other analgesics questionable; increased side effects

High

Ticlopide No more efficacious than aspirin for clots; more side effects

High

Ketorolac Use (especially long-term) associated with GI side effects

High

Amphetamines Addictive; Induce hypertension, angina, and myocardial infarction

High

Long-term use of NSAIDs GI bleeds, renal failure, high blood pressure, heart failure

High

Bisacodyl Long-term use may exacerbate bowel dysfunction

High

Amiodarone May prolong QT interval; questionable efficacy in elderly

High

Fluoxetine (daily dosing) Long half-life may prolong CNS stimulation, sleep disturbances, agitation

High

Nitrofurantoin Renal impairment High Doxazosin Hypotention; anticholinergic effects Low Methyltestosterone Prostatic hypertrophy; cardiac issues High Short acting nifedipine Hypotension; constipation High Clonidine Hypotension; CNS effects Low Mineral oil Risk for aspiration and other side effects High Cimitidine Increased CNS effects (confusion); drug

interactions Low

Ethacrynic acid Hypertension; fluid imbalances Low Estrogens only agents Evidence of carcinogenic potential and

lack of cardio-protective effects in elderly women

Low

Notes: Abbreviations: CNS- central nervous system; NSAIDs- nonsteroidal anti-inflammatory drugs; EPS- extrapyramidal symptoms Anticholinergic effects- may effect several different systems; most notable effects include: ataxia, dry mouth and eyes, blurred vision, constipation, tachycardia, light-headedness urinary retention, confusion, and agitation.

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

Questions???