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
Dosing and administration of Rivastigmine
- Capsule, oral solution, transdermal patch available
- Longer titration period may be needed to decrease GI symptoms
- Take with food
- NO adjustment w/renal or hepatic impairment
ADRs of Rivastigmine
- NV
- Dizziness
- Diarrhea
- HA
- Insomnia
- Depression
- Somnolence
How should a CI be chosen to treat AD?
- No randomized trials demonstrating one better than another
- Best outcomes from continuous, uninterrupted therapy
What NMDA blockers are approved to treat AD?
Memantine
MOA of Memantine
- Specific, noncompetitive NMDA blocker w/moderate affinity (slows glutamatergic exitotoxic neurotoxicity)
- Rapid association and dissociation w/the receptor
- Does not interact w/other receptors, transporters, enzyme systems
What is Memantine approved to treat?
Mod-severe AD
PK of Memantine
- 100% bioavailability
- Rapidly crosses BBB
- Renally excreted as the parent compound
Dosing of Memantine
- XR and oral solution formulations available
- Dose reduction if CrCl less than 30
ADRs of Memantine
- Dizziness
- HA
- Constipation
- HTN
What is the role of combo therapy in AD?
- No trials have assessed dual CI use
- Memantine and donepezil combo is not considered clinically significant, but can be tried in severe AD because minimal side effects
MOA of Vitamin E in AD
- Decrease in free oxygen radicals
- May slow progression of existing AD
- But needed in high doses and there is increased mortality a/w high doses
Vitamin E’s role in AD treatment
- NOT recommended
- Would need high doses, but high doses increases risk of mortality
How could ASA be used to treat AD?
- Vascular disease is a risk factor for AD
- If pt can tolerate it, ASA could help attack vascular risk
- Only 81 mg
How could estrogen be used to treat AD?
We don’t recommend initiating it because of increased thromboembolic events
How could NSAIDs be used to treat AD?
We don’t recommend initiating it (BESIDES ASA) because of CV risk
How could lipid lowering agents be used to treat AD?
Can be used to potentially stabilize plaques, but we aren’t initiating high dose statins
How could B vitamins be used to treat AD?
B6, B9, B12 can help - we can add it because there’s no big risk to taking it
How could Ginkgo biloba be used to treat AD?
Can start a pt on it, but does have a bleeding risk
What pharm therapies can be used to treat non-cognitive symptoms?
- Antipsychotics (haloperidol, atypicals)
- Antidepressants (SSRIs, SNRIs)
- Anticonvulsants (carbamazepine, valproic acid)
- Benzodiazepines
What target symptoms do antipsychotics treat in AD?
- Psychosis
- Disruptive behavior (agitation, aggression)
What target symptoms do antidepressants treat in AD?
Depression
What target symptoms do benzodiazepines treat in AD?
- Anxiety
- Restlessness
- Insomnia
What target symptoms do anticonvulsants treat in AD?
Agitation or aggression
What are the only benzodiazepines used in older patients?
- Lorazepam
- Oxazepam
- Temazepam
What is Caprylidene?
- Medical food that may help the brain of mild-mod AD patients
- May increase TGs
- Caution in pts at risk of ketoacidosis
