3. CaseOverview
Demographics
• 83 y/o
• Female
Situation
Contacted by phone to follow-up on INR results
A-fib
Seen by Pharmacy Services for warfarin management
4. CaseHPI
Recently diagnosed with Alzheimer’s Disease
• Repeats herself
• Tells the same stories repeatedly
• Problems with medication adherence
▫ Repeat doses
▫ Missed doses
▫ Forgets schedule
Her son is her primary caretaker
9. CaseFHx/SHx/Allergies
Social Hx
• Alcohol: Rarely
• Smoking: Unknown
• Caffeine: Occasional
Family Hx
• Father: Deceased (59) – Kidney failure
• Mother: Deceased (74) – Complications of diabetes
Allergies
Substance Reaction
Furosemide Rash, but can tolerate if given w/ diphenhydramine
Hydrochlorothiazide Skin rashes
Nitrofurantoin Pruritic rash on legs, trunk, and upper extremities
Sulfa drugs
10. CaseVitals
7/26/11 • Patient is experiencing
Ht 5’ 4”
unexplained weight-loss
• HR is controlled by PPM
Wt 112 lbs
BMI 19.2
(18.5-25)
BP 119/59
(<120/80 mmHg)
HR 69
(60-100 bpm)
RR 16
(12-20 rpm)
11. CaseLabs 9/20/11
INR 1.9 L
• INR is subtherapeutic (2-3)
• Patient is anemic 7/27/11
▫ Low RBC, Hgb, Hct RBC 3.58 L
▫ Borderline macrocytic (4.0-5.2 /L)
▫ Borderline anisocytosis Hgb 10.9 L
(12.5-16.0 g/dL)
• Renal impairment Hct 33.1 L
(36-46 %)
▫ Low Scr, eGFR
MCV 93
(81.0-97.4 fL)
RDW-CV 14.4
(11.7-14.4 %)
SCr 1.27 H
(0.6-1.2 mg/dL)
eGFR 39 L
(106-132 mL/min)
12. CaseLabs 7/27/11
Albumin
• No vitamin B12 or folate (3.5-5.5 g/dL)
4.1
deficiency K+ 4.1
(3.5-5.1 mEq/L)
• Digoxin levels are high, but Ca2+ 9.3
not toxic (9.0-10.5 mg/dL)
Vitamin B12 756
(211-946 pg/mL)
Folate > 20
(> 3 ng/mL)
1/27/11
Digoxin
(0.5-2.2 ng/mL) 1.2
(0.5-1 ng/mL)
7/22/09
DEXA (T-score) Spine: +1.4
(> -1.0) Femur: -1.1
13. Case Medications
Medication Strength Qty Form Frequency Indication
Triamcinolone acetonide 0.1% - Cream Once daily to rash Rash
Oxybutynin 24hr (Ditropan XL®) 15 mg 1 Tablet Daily Urinary incontinence
Potassium chloride 10 mEq / 7.5 mL Liquid Daily Potassium balance
Pantoprazole (Protonix®) 40 mg 1 Tablet Daily GERD
Digoxin 0.125 mg 1 Tablet Daily CHF
Bumetanide (Bumex®) 1 mg 1 Tablet Daily CHF
Warfarin (Coumadin®) 2.5 mg 2.5 mg daily, except 3.75 mg on Wed A-fib
Lisinopril 5 mg 1 Tablet Daily HTN, CHF
Carvedilol 6.25 mg 1 Tablet Twice daily CHF, HTN
Centrum Silver Chewables® - 1 Tablet Daily None
Patient tried Namenda® once some time in July, but “did not like the
way it made her feel.”
Patient also tried Aricept® once, but did not like it because it made her feel
like a "zombie."
15. AD Description
Alzheimer’s disease (AD) is a common age-related,
chronic debilitating neurodegenerative condition
that is associated with progressive cognitive
decline and profound neuronal loss.
16. AD Epidemiology
• Most common form of dementia in the elderly
▫ 10% of those >65 y/o
▫ 50% of those >85 y/o
• 4.5 million affected in the US
• 18 million affected world-wide
17. AD History
• Discovered in 1907
• Two pathologic alterations
▫ Neuritic plaques
▫ Neurofibrillary tangles
• Full pathology is still
unknown
Dr. Alois Alzheimer
18. AD Pathology
Neuritic plaques
• β-amyloid protein (Aβ)
▫ Breakdown product of a membrane-bound protein
• Imbalance between the production and clearance of Aβ peptides resulting in
aggregation that causes accumulation of Aβ and ultimately leading to AD (Amyloid
Cascade Hypothesis)
• While Aβ sequestered in plaques was at first believed to represent the critical toxic
species, more recent versions of the hypothesis assume Aβ that is not sequestered in
plaques actually drives the disease.
Neurofibrillary Tangles (NFTs)
• Tau protein
▫ Provide stability to microtubules
▫ Mostly found in neuronal cells
▫ Become hyperphosphorylated in AD
21. AD Clinical Presentation
Cognitive
• Memory loss (poor recall and losing items)
• Aphasia (circumlocution and anomia)
• Apraxia
• Agnosia
• Disorientation (impaired perception of time and unable to recognize familiar people)
• Impaired executive function
Noncognitive
• Depression, psychotic symptoms (hallucinations and delusions)
• Behavioral disturbances (physical and verbal aggression, motor hyperactivity,
uncooperativeness, wandering, repetitive mannerisms and activities, and combativeness)
Functional
• Inability to care for self (dressing, bathing, toileting, and eating)
22. AD Staging
Stages of Alzheimer's Disease
Mild Patient has difficulty remembering recent events. Ability to manage finances,
(MMSE score 26–18) prepare food, and carry out other household activities declines. May get lost
while driving. Begins to withdraw from difficult tasks and to give up hobbies.
May deny memory problems.
Moderate Patient requires assistance with activities of daily living. Frequently
(MMSE score 17–10) disoriented with regard to time (date, year, season). Recall for recent events
is severely impaired. May forget some details of past life and names of family
and friends. Functioning may fluctuate from day to day. Patient generally
denies problems. May become suspicious or tearful. Loses ability to drive
safely. Agitation, paranoia, and delusions are common.
Severe Patient loses ability to speak, walk, and feed self. Incontinent of urine and
(MMSE score 9–0) feces. Requires care 24 hours a day, 7 days a week.
23. AD Diagnosis
Progressive change in
MMSE
memory or function
Clinical diagnosis made mostly DSM-IV criteria
by ruling out other possibilities Dementia AHRQ guidelines
• DSM-IV-TR Medication-induced
Medication review AHRQ guidelines
dementia
• National Institutes of
Health-Alzheimer’s Disease
Hypothyroidism
and Related Disorders Abnormal lab tests
Abnormal physical exam
Abnormal
B12 Deficiency AAN guidelines
Systemic illness
Association (NIH-ADRDA)
▫ Published in 2011 Vascular dementia
Abnormal Hydrocephalus
▫ Used mostly for research CT or MRI/Optional
Tumors
NINDS criteria
purposes Subdural hematoma
Yes DSM-IV criteria
Depressed mood Depression
AHRQ guidelines
NINCDS-ADRDA
Alzheimer’s disease Atypical disorders
criteria
Refer for assessment
24. AD Prognosis & Treatment Goals
Prognosis
• Cannot cure or prevent Alzheimer’s
▫ Current therapy does not affect the progression of the disease
• Survival following diagnosis is typically 4 to 6 years
Treatment Goals
• Treat cognitive symptoms
• Treat psychiatric and behavioral sequelae
• Preserve cognitive functioning as long as possible
25. AD Non-pharmacologic therapy
• Disease-state education Table 63-3 Basic Principles of Care for the Alzheimer's Patient
• Consider vision, hearing, or other sensory impairments.
• End-of-life planning • Find optimal level of autonomy and adjust expectations for patient
performance over time.
• Handling behavioral
• Avoid confrontation. Remain calm, firm, and supportive if the patient
symptoms becomes upset.
• Maintain a consistent, structured environment with stimulation level
• Caring for the caregiver appropriate to the individual patient.
• Provide frequent reminders, explanations, and orientation cues.
Employ guiding, demonstration, and reinforcement.
• Reduce choices, keep requests and demands of the patient simple,
and avoid complex tasks that lead to frustration.
• Bring sudden declines in function and the emergence of new
symptoms to professional attention.
26. AD Pharmacologic therapy
Only 5 FDA-Approved Drugs
Drug name Brand name Approved For FDA Approved
Cholinesterase Inhibitors (ChEIs)
Galantamine Razadyne® Mild to moderate 2001
Rivastigmine Exelon® Mild to moderate 2000
Donepezil Aricept® All stages 1996
Tacrine Cognex® Mild to moderate 1993
NMDA Antagonists
Memantine Namenda® Moderate to severe 2003
27. AD Cholinesterase Inhibitors
Actions
Galantamine Oral: 4 mg BID
(Razadyne®) (up to 12 mg BID)
Oral, ER: 8 mg daily
ACh (up to 24 mg daily)
Choline + Acetic acid Rivastigmine Oral: 1.5 mg BID
(Exelon®) (up to 6 mg BID)
Patch: 4.6 mg/24 hr,
9.5 mg/24 hr
• Increase concentration of Ach Donepezil Oral: 5, 10, or 23 mg
daily
• Improve alertness and cognitive (Aricept®)
activity
28. AD Cholinesterase Inhibitors
Adverse Reactions
Galantamine Oral: 4 mg BID
Related to cholinergic effects… (Razadyne®) (up to 12 mg BID)
Oral, ER: 8 mg daily
• N/V/D Most common (up to 24 mg daily)
• Dizziness
Rivastigmine Oral: 1.5 mg BID
• Headache (Exelon®) (up to 6 mg BID)
• Urinary incontinence Patch: 4.6 mg/24 hr,
9.5 mg/24 hr
• Fatigue
• Sweating Donepezil Oral: 5, 10, or 23 mg
daily
(Aricept®)
• Salivation
• Bradycardia
• Personality changes
35. AD NMDA antagonists
Interactions
• No significant drug
interactions Memantine Oral: 5 mg/day
(up to 20 mg/day)
(Namenda®)
Oral, ER: 7 mg daily
(up to 28 mg daily)
36. AD NMDA antagonists
Monitoring
• Mental status
• Blood pressure Memantine
(Namenda®)
Oral: 5 mg/day
(up to 20 mg/day)
• Renal function Oral, ER: 7 mg daily
(up to 28 mg daily)
37. AD Unproven therapies
• Estrogen
▫ Lower incidence of AD in women receiving HRT
• NSAIDs
▫ Prevent damage from neuroinflammation
• Statins
▫ Apolipoprotein E (ApoE) linked to AD
• Vitamin E
▫ Antioxidant to counter oxidative stress
* None of the therapies above have shown success in clinical trails *
38. AD Secondary therapies
• Antipsychotics
▫ Used to treat behavioral symptoms
▫ Most of benefit for their neuroleptic effects
▫ Use non-pharmacologic approaches first
• Benzodiazepines
▫ Also used to treat behavioral symptoms and agitation
▫ May worsen cognition
▫ Can increase fall risk
• Antidepressants
▫ Depression is a common comorbidity in AD
▫ Citalopram and sertraline have the most evidence to support their use
• Anticonvulsants
▫ Used for mood-stabilization
▫ Not enough evidence to recommend use
40. CaseA & P
1. Alzheimer’s Disease
• No remaining pharmacologic options
• Monitor cognitive capacity and recommend lifestyle
modifications as necessary
• Continually assess impact on adherence to other
medications (especially warfarin)
• Suggest resources for the son/caregiver
41. CaseA & P
2. A-fib
• CHADS2 = 3
▫ Lifetime anticoagulation with warfarin is therefore appropriate in this patient
• Patient’s INR is still subtherapeutic
▫ Increased weekly dose by 7%
3. Heart failure
• Receiving recommended pharmacotherapy for Stage C heart failure
• Well-controlled at this time
4. Hypertension
• BP is stable and at goal
• Note that low diastolic BP could reduce cerebral perfusion and worsen AD
42. CaseA & P
5. Urinary incontinence
• Anticholinergic effects of Ditropan XL® may cause agitation and confusion which
would amplify her AD
• However, no negative effects were recorded after initiating this medication
6. Chronic anemia
• Check for s/sx of bleeding
• Check serum iron, TBIC, t-sat, and ferritin w/ next lab draw
7. Meningioma/Colon caner
• Patient has refused additional intervention
• Monitor for s/sx of bleeding
• Occasionally reassess patient’s interest in treatment
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