AD- Acetylcholinesterase Inhibitors DI

Question 1

Acetylcholinesterase inhibitors used in PD

Answer 1

donepezil, rivastigmine, galantamine

Question 2

donepezil indication

Answer 2

mild-severe AD

Question 3

donepezil dosing

Answer 3

1 tab PO HS with or without food, can be moved to the morning if patient has sleep disturbances/vivid dreams

Question 4

donepezil titration

Answer 4

5mg QD x4-6 weeks –> 10mg QD if tolerated –> MDD 23mg QD after 3 months

Question 5

donepezil dose adjustment for hepatic and renal dysfunction

Answer 5

No dose adjustments needed!

Question 6

donepezil side effects

Answer 6

symptomatic bradycardia, rare cases of rhabdomyolysis and/or NMS

Question 7

donepezil PK/PD

Answer 7

long half-life of 72 HOURS, metabolized by 2D6 and 3A4

Question 8

rivastigmine indications

Answer 8

capsule: mild-severe AD and mild-moderate Parkinson’s dementia

patch: mild-severe AD

Question 9

rivastigmine capsule dosing

Answer 9

6-12mg/day BID usual dose; start with 1.5mg BID and increase by 3mg q2w

Question 10

rivastigmine patch dosing

Answer 10

initial dose is 4.6mg/24hrs –> 9.5mg/24hrs after tolerating 4 weeks of treatment –> may be increased to 13.3mg/24hrs

Question 11

What strength of rivastigmine patch can you use in patients <50kg or with mild-moderate hepatic dysfunction?

Answer 11

4.6mg/24hr

Question 12

Conversion from capsule or PO solution of rivastigmine to patch

Answer 12

<6mg of PO –> 4.6mg/24hr
6-12mg PO –>9.5mg/24hr

Apply the first patch on the day after the last PO dose

Question 13

rivastigmine PK/PD

Answer 13

half-life of 2 hours
NOT metabolized by 2D6 and 3A4

Question 14

rivastigmine capsule ADEs

Answer 14

GI upset- start low and go slow or take with food

Question 15

rivastigmine patch ADEs

Answer 15

site reactions, less GI upset than the capsule

Question 16

galantamine indications

Answer 16

mild-moderate AD

Question 17

Do NOT use galantamine in what patients?

Answer 17

ESRD and severe hepatic impairment patients

Question 18

galantamine IR dosing

Answer 18

4mg BID x4 weeks –> 8mg BID –> 12mg BID

Question 19

galantamine ER dosing

Answer 19

8mg QD–> 16mg QD–> 24mg QD

Question 20

Recommended MDD of galantamine in patients with moderate renal or hepatic impairment

Answer 20

12mg

Question 21

galantamine PK/PD

Answer 21

half-life of 7 hours
metabolized by 2D6 and 3A4

Question 22

Acetylcholinesterase inhibitors MoA

Answer 22

block acetylcholinesterase to block ACh metabolism and enhance the ACh already present

Question 23

Do ACh inhibitors change the underlying patho?

Answer 23

No! We’re trying to maximize the amount of ACh that we can even though we’re still losing cholinergic neurons and ACh

Question 24

Side effects of ACh inhibitors: cholinergic side effects

Answer 24

sialorrhea, lacrimation, urination, defecation, GI (emesis, diarrhea), emesis

Question 25

Side effects of ACh inhibitors: CNS

Answer 25

HA, insomnia, vivid dreams

Question 26

Side effects of ACh inhibitors: cardiac

Answer 26

bradycardia, syncope, heart block, hypotension

Question 27

Side effects of ACh inhibitors: GI

Answer 27

anorexia, weight loss

Question 28

ACh inhibitors CI

Answer 28

Patients with baseline bradycardia/known cardiac conduction system disease due to risk of syncope, falls, fractures

Question 29

Tips for starting ACh inhibitors

Answer 29

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