Medication Management of the Alzheimer Patient

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Medication Management of the Alzheimer Patient

• Dr. J. Lance Nickelson, Pharm. D.
• Assistant Professor of Clinical Pharmacy
  Practice, ULM School of Pharmacy, St. Patricks
  Hospital

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Introduction and Background

• Alzheimers disease is a disease in which nerve
  cells in the brain die.
  
• Symptoms of the disease include
• Decreased memory, judgment and thinking ability
• Eventual decrease in motor functioning and
  ability to perform activities of daily living
  (ADLs)
  
• Behavioral disturbances

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Introduction and Background

• It is important to note that to date, all
  approved drugs and other drugs used in the
  treatment of Alzheimers mainly target symptoms
  of the disease rather than modify or change the
  disease process.
• No cure to date.

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Pathophysiology/Cause of AD

• Hallmark feature of AD in the presences of
  amyloid plaques in the brain.
  
• Plaques typically develop first in areas of the
  brain responsible for memory and cognition
  
• Also, tau proteins (a structural component of
  nerve cells) collapse and form neurofibrillary
  tangles that cause nerve cells to die

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Amyloid Proteins

• Amyloid protein in AD is called beta-amyloid
• Beta-amyloid is formed when large proteins called
  amyloid precursor proteins are broken down by
  enzymes
  
• AD patients accumulate large amounts of
  beta-amyloid
  
• This excessive beta-amyloid can clump and leads
  to formation of fibrills (insoluble particle)
  which then make up the amyloid plaques which is
  the hallmark of AD.

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New Treatments

• Most of the promising new treatments in
  development for AD is aimed at modulating the
  formation of amyloid plaques
  
• Many of these new treatments are based on the use
  of vaccines which use the immune system to
  decrease the formation of amyloid plaques.

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Vaccines for AD

• Alzehemed
• a vaccine from Neurochem
• Completed Phase II trials
• Mechanism
• Prevent and stop formation and deposition of
  amyloid fibrils in the brain by binding to
  soluble beta-amyloid
  
• Increase the clearance of soluble beta-amyloid
• Inhibit the inflammation responses associated
  with amyloid build-up

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Vaccines for AD

• Elan Pharmaceuticals developing a vaccine to
  attack the amyloid plaques
  
• Completed Phase I
• Issues with vaccines
• Historically, one vaccine was associated with
  risk of meningitis
  
• Risks involved with modulation of the immune
  system

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Other Treatments

• Eli Lilly is developing a drug to block the
  formation of beta-amyloid by inhibiting the
  enzyme that breaks down the amyloid precursor
  protein

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Ancillary Treatments

• Remember that processes involved with nerve cell
  death included oxidative stress and inflammation
  
• Therefore, drugs with antioxidant and
  anti-inflammatory properties may have some role
  in AD
  
• Vitamin E and C, NSAIDS, statins
• Exact role and safety still being identified

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Current Treatments

• Current treatments are symptomatic
• Aimed at slowing progression of certain symptoms
  rather than altering the disease process
  
• Symptom domains of AD (ABCs)
• ADLs
• Behavior
• Cognition

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ABCs of AD

• ADLs
• Performance of activities of daily living
• Behaviors
• Behavioral disturbances
• Agitation, depression, psychosis, etc.
• Cognition
• Memory, performance of cognitive tasks
• Note that the symptom domains are not exclusive
  or separate. Improvement in 1 domain can spill
  over into another.

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Current Drug Treatment of AD

• For this presentation, the drugs will be
  discussed as they relate to their particular
  strengths in regards to specific symptom
  domains.
• Due to the different strengths, many AD patients
  will be on more than 1 medication.

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Cognition

• Cognition and short-term memory is based on the
  actions of acetylcholine (ACh)
  
• Therefore drugs that interfere with acetylcholine
  can worsen memory or induce delirium
  
• Drugs that increase ACh activity can protect
  cognition and memory

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Cognition

• It is important to avoid drugs that can impair
  cognition
  
• Anticholinergics, sedatives, narcotics, etc.
• Remove offending drugs whenever possible
• Add an Acetylcholinesterase inhibitor

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Acetylcholinesterase Inhibitors

• Inhibit the enzyme that breaks down Ach
• Cholinergic neurons must still be present
• These drugs help maintain or slow progression of
  cognitive impairment vs. improvement of
  cognition
  
• Keys to maximizing benefit
• Start early in the disease process
• Maximize dose as tolerated
• Continuation of treatment

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Acetylcholinesterase Inhibitors

• Primary side effects are gastrointestinal
• Nausea, vomiting, anorexia
• Minimized by titrating (increasing) the dose
  slowly
  
• Agents
• Donepezil (Aricept)
• Exelon (rivastigmine)
• Reminyl (galantamine)

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Acetylcholinesterase Inhibitors

• Little if any difference in efficacy
• Equally effective
• Some differences in dosing schedule
• Aricept the easiest
• Strength is in improving cognitive abilities

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ADLs

• Ability to perform ADLs can be of particular
  concern to caregivers
  
• Eating, bathing, toileting and dressing
• No specific neurotransmitter responsible for
  performance of these tasks, however, the newest
  approved drug for AD appears to have the greatest
  effect on this symptom domain

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Memantine (Namenda)

• A NMDA-receptor antagonist
• Blocks the effects of glutamate (an excitatory
  neurotransmitter)
  
• Appears to decrease oxidative stress in the
  central nervous system
  
• Dosed twice daily (up to 10mg BID)
• Greatest efficacy in maintaining ability to
  perform ADLs

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Current Drug Treatment

• Studies indicate that best treatment is the use
  of an acetylcholinesterase inhibitor (cognition)
  plus Namenda (ADLs)
  
• Combination treatment has been shown more
  effective than monotherapy
  
• However, improvement of the patient is not seen
  long-term
  
• What is seen is maintenance (best case) or
  slowing of the progression (usual outcomes)

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Behaviors

• Behavioral changes in AD are also of particular
  concern to caregivers
  
• Agitation, combativeness, wandering, depression,
  hallucination, delusions, decreased sleep
  
• As noted earlier improvement of cognition may
  lead to improvement in behaviors
  
• But in many cases, specific behaviors may need
  addressing

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Behaviors

• Often behavioral symptoms of AD will require
  treatment with drugs used in psychiatry
  
• Antidepressants
• Prozac, Paxil, Lexapro, Remeron, Effexor
• Antipsychotics
• Zyprexa, Seroquel, Abilify, Risperdal, Haldol
• Benzodiazepines
• Ativan, Klonopin, Restoril

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Drug Treatment of Behaviors in AD

• 3 Critical questions that must be answered first
• 1. Can the behavior be addressed without
  medication?
  
• 2. Is the behavior amenable to drug therapy?
• 3. Is the behavior a side effect or result of
  current drug therapy?

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Drug Treatment of Behaviors in AD

• If the decision to use drug therapy is made then
  selection of appropriate drug is vital.
  
• Antidepressant vs. antipsychotic
• Once drug therapy is started, monitoring for
  effectiveness and tolerability becomes critical
  
• Caregiver should be comfortable discussing use of
  psychiatric meds with providers (physicians,
  nurses and pharmacists)

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Questions