Dementia and Pharmacy Intervention

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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
Zubenko et al. Harvard Rev Psychiatry 2000
• Gaba-ergic system
 Potential increase in
response to
potentiation at GABA
receptors
• Adrenergic system
 Impaired baroreceptor
function may result in
orthostasis
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
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
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 Delirium
Medication Class
Benzodiazepines
Medication
Medication Class
Antidepressants
Opioids
Dopaminergic Agents
Corticosteroids
Amantadine
Levodpa
Bromocriptine
Prednisone
NSAIDs
Diclofenac
Ibuprofen
Sulindac
Indomethacin
Salicylic acid
Ketoprofen
Antihypertensives
Enalapril
Captopril
Lisinopril
Reserpine
Clonidine
Methyldopa
Nifedipine
Verapamil
Atenolol
Metoprolol
Propranolol
Antipsychotics
Clozapine * 
Fluphenazine
Haloperidol
Loxapine
Olanzapine 
Perphenazine
Quetiapine 
Risperidone
Thioridazine 
Ziprasidone
Antiarrhythmics
Amiodarone
Lidocaine
Quinidine
Tocainide
Anticholinergics
Atropine 
Benztropine 
Scopolamine 
Tolterodine 
Antimicrobials
Tobramycin
Bactrim
Linezolid
Other Agents
Antiasthmatics
Theophylline
Anticonvulsants
Phenytoin
Acetazolamide
Lamotrigine
Pregabalin
Valproic Acid*
Digoxin
Alcohol
withdrawl
Lithium *
* Documented incidence from clinical trials
 Medications that have anticholinergic effects
which can be associated with cognitive impairment
Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management:
2nd ed. ASHP 2010; Chapter 15: Delirium.
Amitriptyline 
Desipramine 
Doxepin 
Imipramine 
Protriptyline 
Mirtazapine 
Fluoxetine
Paroxetine
Sertraline
Lorazepam
Diazepam
Clonazepam
Alprazolam
Triazolam
Clorazepate
Fentanyl *
Meperidine *
Morphine *
Medication
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
Propoxyphene and combinations
Indomethacin
Pentazocine
Trimethobenzamide
Muscles relaxants and
antispasmodics
Flurazepam
Amitriptyline
Doxepine
Meprobamate
Specific dosing of
benzodiazepines
 Lorazepam > 3 mg
 Oxazepam > 60 mg
 Alprazolam > 2 mg
 Temazepam > 15 mg
 Triazolam > 0.25 mg
Long-acting benzodiazepines
 Chlordiazepoxide
 Diazepam
 Quazepam
 Halazepam
 Chlorazepate
Concern
Demonstrates analgesic effects similar to
acetaminophen with adverse effects of
narcotics
Produces most CNS effects of the
NSAID class
Narcotic with several CNS effects:
confusion and hallucinations
Poor antiemetic effects; potential for
EPS
Poorly tolerated in elderly;
anticholinergic effects; increase fall risk
Severity Rating
Low
High
High
High
High
Extremely long half-life cause prolonged
side effects of sedation and falls
Potent anticholinergic; sedating
Potent anticholinergic; sedating
Highly addictive anxiolytic
Doses ranging higher than those
suggested demonstrate little benefit with
increased side effects compared to
smaller doses
High
Long half-life produces prolonged
sedation and increased risk for falls
High
High
High
High
Abbreviated Beers Criteria
Disopyramide
Digoxin
Short-acting dipyridamole
Methyldopa
Reserpine > 0.25 mg
Chlorpropamide
GI antispasmodics
 Dicyclomine
 Hyoscyamine
 Belladonna alkaloids
 Clidiniumchlordiazapoxide
Anticholinergics/Antihistamines
 Chlorpheniarmine
 Diphenhydramine
 Hydroxyzine
 Cyproheptadine
 Promethazine
Diphenhydramine
Ferrous Sulfate > 325 mg/day
Barbiturates (except
Phenobarbital)
Particular antiarrhythmic may induce
heart failure in elderly; also
anticholinergic effects
Closely monitor renal clearance and
levels to prevent toxicity
Potential for orthostatic hypotenstion;
long-acting formulation only in those
with prosthetic heart valves
Bradycardia; may potentiate depression
May induce depression, impotence,
sedation, orthostatic hypotension
Long half-life may prolong
hypoglycemia
Increased anticholinergic effects;
efficacy uncertain
High
Potent anticholinergic
High
Confusion and sedation; use lowest
possible dose in allergic reactions
High doses not dramatically absorbed;
constipation greatly increased
Highly addictive; harmful side effects
High
Low
Low
High
Low
High
High
Low
High
Abbreviated Beers Criteria
Meperidine
Ticlopide
Ketorolac
Amphetamines
Long-term use of NSAIDs
Bisacodyl
Amiodarone
Fluoxetine (daily dosing)
Nitrofurantoin
Doxazosin
Methyltestosterone
Short acting nifedipine
Clonidine
Mineral oil
Cimitidine
Ethacrynic acid
Estrogens only agents
Advantage over other analgesics
questionable; increased side effects
No more efficacious than aspirin for
clots; more side effects
Use (especially long-term) associated
with GI side effects
Addictive; Induce hypertension, angina,
and myocardial infarction
GI bleeds, renal failure, high blood
pressure, heart failure
Long-term use may exacerbate bowel
dysfunction
May prolong QT interval; questionable
efficacy in elderly
Long half-life may prolong CNS
stimulation, sleep disturbances, agitation
Renal impairment
Hypotention; anticholinergic effects
Prostatic hypertrophy; cardiac issues
Hypotension; constipation
Hypotension; CNS effects
Risk for aspiration and other side effects
Increased CNS effects (confusion); drug
interactions
Hypertension; fluid imbalances
Evidence of carcinogenic potential and
lack of cardio-protective effects in
elderly women
High
High
High
High
High
High
High
High
High
Low
High
High
Low
High
Low
Low
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
 Medical condition
- Pain control
- 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???
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