Alzheimer's Flashcards
Goals for treatment of cognitive impairment
- AD treatment is to improve symptoms and reverse cognitive decline
- CURRENTLY, AVAILABLE DRUGS CANNOT DO THIS
- Attainable goal is to maintain the patient’s independence for as long as is possible
- DRUGS MAY SLOW LOSS OF MEMORY AND COGNITION AND PROLONG INDEPENDENT FUNCTION
Four drugs approved for treatment
Cholinesterase Inhibitors:
- 1. Donepezil, 2. galantamine, 3. rivastigmine
NDMA Inhibitors:
- 4. Memantine
(blocks receptors for N-methyl–D-aspartate)
Pathophys of Alzheimer’s (AD)
- Early in Hippocampus (memory)
- Later in Cerebral Cortex (speech, perception, higher function) and subsequent decline in Cerebral volume
Reduced Cholinesterase Transmission
- Levels of acetylcholine 90% below normal
- Acetylcholine is important for neurotransmitters and critical for forming memories
Drugs for cognitive impairment GOALS
- Improve symptoms + reverse cognitive decline
- #1 goal is to maintain independence for as long as possible
Drug Therapy for AD (3 points)
- Tx can yield improvement that is statistically significant but clinically marginal
- Cholinesterase Inhibitors may delay or slow progression but WILL NOT STOP IT
- Cholinesterase BLOCKERS such as: first gen. antihistamines, antipsychotics, tricyclic antidepressants CAN REDUCE RESPONSE TO CHOLINESTERASE INHIBITORS
Cholinesterase Inhibitors: 3 Drugs and Generally What they do
- Donepezil
- Rivastigmine
- Galantamine
- Prevent breakdown of acetylcholine
- May slow Progression of disease
- Only 3 are recommended for use but have equivalent benefits
Cholinesterase Inhibitors Dosing
Donepezil: (first-line treatment) mild-moderate: - 5-10mg PO q AM >>> Start: 5mg PO q AM x 4-6 weeks >>> Then: may increase to 10mg q AM
MAX is 10mg/day
moderate-severe : - 10-23mg PO q AM >>> Start: 5mg PO q AM x 4-6 Weeks >>> Then: Increase to 10mg PO q AM 3 months >>> Then: Increase to 23mg PO q AM
- MAX is 23mg/day*
- This 23mg higher dose is associated with more adverse side effects*
- Do not cut/crush/chew 23mg dose*
rivastigmine: mild to severe
» SEVERE INDICATION ONLY FOR TRANSDERMAL
Dosing: 1.5mg PO BID, increase by 1.5mg q2weeks, retitrate if dose interrupted MAX 12mg/day
galantamine: mild to moderate
8-12mg PO BID
start 4mg PO BID q4weeks MAX 24mg/day
FDA APPROVAL OF Cholinesterase Inhibitors for Severity
Mild-Severe: PO donepezil and TRANSDERMAL rivastigmine
Mild-Moderate: PO rivastigmine and PO galantamine
Cholinesterase Inhibitors Adverse Side Effects
- DONT STOP IMMEDIATELY as you could see rebound cognitive decline
- TAPER DOWN WHEN STOPPING
Bradycardia: resulting in decreased cardiac output and increase risk of falls
-STOP WITH CV RISK and COGNITIVE BENEFIT IS LACKING
GI Upset: diarrhea, dyspepsia
Dizziness
Headache
Bronchoconstriction: Because of this, use with caution in patients with asthma and COPD
Typical Cholinergic Side Effects:
TOXIC SIDE EFFECTS:
- hallucinations, agitation, aggressive behavior, abnormal dreams, nightmares, delusions, irritability, aggression, increased libido, restlessness
- WHAT DO YOU DO ABOUT HALLUCINATIONS?????
Cholinesterase Inhibitors Dosing Notes
- AM dosing is preferred due to nightly dosing causing nightmares
- Switch to PM dosing if daytime nausea occurs
- ONLY 1 CHOLINESTERASE INHIBITOR CAN BE GIVEN AT A TIME
NDMA Inhibitors
N-Methyl-D-Aspartate (NDMA) receptor antagonist
—— Memantine
Mod-Sev AD
- Modest outcomes
Usually give in combo with cholinesterase inhibitors as symptoms progress
May given as monotherapy if cholinesterase inhibitors are not tolerated or ineffective
Renal Clearance
- meds need renal dosing for sev renal disease
- If GFR is lower than 30’
WHEN TO ADD AS SECOND DRUG?
The addition of memantine should be considered for treatment of cognitive and functional symptoms
in patients with moderate to severe Alzheimer disease or mixed dementia who are already receiving
a cholinesterase inhibitor.
Antidepressants
- Depression affects 25% of AD pts and is associated with wandering, agitation, and aggression
- Mixed results is studies of depression in AD pts
- Thought, experts do recommend trying them for depressed mood
- Citalopram effective for agitation + reducing caregiver stress
> May also be as effective as risperidone for behavioral and psychotic symptoms - Sertraline may also improve behavior and functioning and reduce caregiver stress
Atypical Antipsychotics
- Agitation or psychosis that is severe, distressing, or significant to the patient or causes the patient to act in ways that create dangers to themselves or others
- Apripiprzaole, risperidone, olanzapine most effective
- Reserve haloperidol for emergent situations such as acute delirum
- Benefits are small at best
Benzodiazepines
- GENERALLY AVOID
- Associated with adverse effects in elderly pts and increased mortality
- Reserve for acute crisis (agitation, alcohol withdrawal, severe anxiety)
Buspirone Indications
Indications: mild-mod agitation, anxiety
