Alzheimer's Flashcards
Environmental and other risk factors of Alzheimer’s
- Age
- Reduced brain size
- Low education/occupation
- Head injury
- Down’s Syndrome
- Depression
- Herpes simplex
- Vascular disease
What is the definitive marker to diagnose AD and when can it be diagnosed?
Only definitive marker - neurofibrillary tangles (found postmortem)
Meds a/w memory loss
- Anticholinergics
- Benzodiazepines (and other sedatives)
- Opioids
- Antipsychotics, anticonvulsants
- NSAIDs
- H2 blockers
- Digoxin
- Amiodarone
- Steroids
- Anti-HTNs
Stages of AD
- Mild cognitive impairment
- Mild AD (MMSE 26-18)
- Moderate AD (MMSE 17-10)
- Severe AD (MMSE 9-0)
What pharm therapy can prevent AD or stop accumulation of B-amyloid?
None
What do current pharm therapies aim to treat in AD?
- Cholinergic system (cholinesterase inhibitors to stop breakdown of ACh, keep ACh in synapses)
- Glutamatergic neurotransmission (NMDA antagonist)
What cholinesterase inhibitors are FDA approved for mild-mod AD?
- Donepezil hydrochloride
- Galantamine hydrobromide
- Rivastigmine tartrate and transdermal
How does efficacy vary between the cholinesterase inhibitor agents?
All have similar efficacy
Describe the efficacy of cholinesterase inhibitors in the first 6 months and then after
- First 6 months: 1-1.5 pt MMSE improvement, 2.8-4 pt ADAS-Cog improvement
- After 6 months: declined efficacy but still better than not treating
How does the average AD patient not on meds decline on MMSE and AGAS-Cog?
- 2-4 point decline on MMSE
- 7 point decline on AGAS-Cog
When is an AD therapy considered effective?
If decline is less than:
- 2-4 points on MMSE
- 7 points on AGAS-Cog
MOA of Donepezil
Reversible cholinesterase inhibitor
What is Donepezil specific for?
- AChE but NOT butyrylcholinesterase
- Results in fewer peripheral adverse effects (NV, diarrhea)
Dosing of donepezil?
- Take at lunch to lessen likelihood of nightmares and vivid dreams
- NO adjustment required for hepatic/renal dysfunction
How long does donepezil stabilize AD?
6-12 months (followed by a gradual decline over a 5 year period)
How can Donepezil be given to pts with mod-severe AD?
High dose (after being on low-mid dosing for 3 months)
Drug interactions with Donepezil
- Anticholinergics
- NSAIDs (higher risk for GI bleeding)
- Theoretical risk w/CYP2D6 or 3A4 inhibitors
ADRs of Donepezil
- NV
- HA
- Diarrhea
- Insomnia
- Pain
- Dizziness
MOA of Galantamine
- Inhibits AChE
- Modulates nicotinic receptors (increased release and enhancement of cholinergic function)
Dosing and administration of Galantamine
- Twice daily
- IR, ER, and oral solution formulations available
- Adjusted with hepatic/renal impairment
How should dosing of Galantamine be adjusted in hepatic/renal impairment?
Do NOT exceed 16 mg/day in hepatic or renal (CrCl less than 70)
When is Galantamine contraindicated?
- CrCl less than 9
- Severe hepatic impairment
ADRs of Galantamine
- NV
- Dizziness
- Diarrhea
- Abnormal dreams
- HA
- Depression
- Insomnia
- Wt loss
MOA of Rivastigmine
- Reversible cholinesterase inhibitor (but very slow dissociation from AChE)
- Substantially inhibits butyrylcholinesterase
