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???