Alzheimer's

Question 1

Describe the pathophysiology behind Alzheimer’s Disease

Answer 1

Signature lesions (amyloid plaques and neurofibrillary tangles) cause neuronal damage through dysregulated glutamate activity resulting in loss of cholinergic cells and activity.

Question 2

Medications that can contribute to cognitive impairment

Answer 2

Benzos, sedative hypnotics (eg. zolpidem), anticholinergics, opioids, antipsychotics, anticonvulsants

Question 3

How are cholinesterase inhibitors useful in Alzheimer’s disease (mechanism of action)

Answer 3

Cholinergic hypothesis assumes cholinergic cell loss is the cause of memory and cognitive impairment in Alzheimer’s. Cholinesterase inhibitors increase cholinergic activity by blocking cholinesterase from metabolizing acetylcholine, thereby helping with cognitive symptoms

Question 4

Name the cholinesterase inhibitor(s) and any unique features

Answer 4

Rivastigmine
Galantamine
Donepezil
All considered equally effective in mild-moderate, but donepezil is also indicated in severe, rivastigmine is avail as a patch

Question 5

What to keep in mind when checking scripts for cholinesterase inhibitors

Answer 5

-concurrent use of anticholinergic meds should be avoided
-washout period is recommended when switching between
-gradual dose titration improves tolerability; most common AE is GI sx (n/v/d) take w food
-rivastigmine and galantamine have short half lives so need to be restarted from a low dose if tx interrupted for several days
-prolonged benefit with long term use, potential increase in speed of cognitive decline when discontinued

Question 6

How does memantine work?

Answer 6

NMDA antagonist that blocks glutaminergic neurotransmission (which causes neuronal damage) which has a neuroprotective effect

Question 7

What is memantine used for?

Answer 7

moderate to severe Alzheimer’s
as monotherapy and in combination with donepezil

Question 8

Most common side effects for mematine?

Answer 8

well-tolerated
headache, constipation, confusion, dizziness