AD- Acetylcholinesterase Inhibitors DI Flashcards
Acetylcholinesterase inhibitors used in PD
donepezil, rivastigmine, galantamine
donepezil indication
mild-severe AD
donepezil dosing
1 tab PO HS with or without food, can be moved to the morning if patient has sleep disturbances/vivid dreams
donepezil titration
5mg QD x4-6 weeks –> 10mg QD if tolerated –> MDD 23mg QD after 3 months
donepezil dose adjustment for hepatic and renal dysfunction
No dose adjustments needed!
donepezil side effects
symptomatic bradycardia, rare cases of rhabdomyolysis and/or NMS
donepezil PK/PD
long half-life of 72 HOURS, metabolized by 2D6 and 3A4
rivastigmine indications
capsule: mild-severe AD and mild-moderate Parkinson’s dementia
patch: mild-severe AD
rivastigmine capsule dosing
6-12mg/day BID usual dose; start with 1.5mg BID and increase by 3mg q2w
rivastigmine patch dosing
initial dose is 4.6mg/24hrs –> 9.5mg/24hrs after tolerating 4 weeks of treatment –> may be increased to 13.3mg/24hrs
What strength of rivastigmine patch can you use in patients <50kg or with mild-moderate hepatic dysfunction?
4.6mg/24hr
Conversion from capsule or PO solution of rivastigmine to patch
<6mg of PO –> 4.6mg/24hr
6-12mg PO –>9.5mg/24hr
Apply the first patch on the day after the last PO dose
rivastigmine PK/PD
half-life of 2 hours
NOT metabolized by 2D6 and 3A4
rivastigmine capsule ADEs
GI upset- start low and go slow or take with food
rivastigmine patch ADEs
site reactions, less GI upset than the capsule
galantamine indications
mild-moderate AD
Do NOT use galantamine in what patients?
ESRD and severe hepatic impairment patients
galantamine IR dosing
4mg BID x4 weeks –> 8mg BID –> 12mg BID
galantamine ER dosing
8mg QD–> 16mg QD–> 24mg QD
Recommended MDD of galantamine in patients with moderate renal or hepatic impairment
12mg
galantamine PK/PD
half-life of 7 hours
metabolized by 2D6 and 3A4
Acetylcholinesterase inhibitors MoA
block acetylcholinesterase to block ACh metabolism and enhance the ACh already present
Do ACh inhibitors change the underlying patho?
No! We’re trying to maximize the amount of ACh that we can even though we’re still losing cholinergic neurons and ACh
Side effects of ACh inhibitors: cholinergic side effects
sialorrhea, lacrimation, urination, defecation, GI (emesis, diarrhea), emesis
Side effects of ACh inhibitors: CNS
HA, insomnia, vivid dreams
Side effects of ACh inhibitors: cardiac
bradycardia, syncope, heart block, hypotension
Side effects of ACh inhibitors: GI
anorexia, weight loss
ACh inhibitors CI
Patients with baseline bradycardia/known cardiac conduction system disease due to risk of syncope, falls, fractures
Tips for starting ACh inhibitors
D/C other anticholinergic meds
Monitor side effects (reduce dose or D/C if ADEs are intolerable, switch agents if intolerant to one, move to AM dosing if there are sleep disturbances, take with food or move to HS dosing if nausea occurs)
Monitor efficacy via caregiver report, mental status exam, effects on ADLs and behavior
