Dementia drugs

Question 1

Cholinesterase-inhibitors?

Answer 1

Donepezil, rivastigmine, galantamine

Question 2

MOA of cholinesterase-inhibitors?

Answer 2

Blocks enzymatic
breakdown of CNS
synaptic ACh →
prolongs synaptic effect
of ACh. Not specific for
n or m cholinergic
receptors.
The central cholinergic
system, particularly the
components in the basal
forebrain, degenerates in
many diseases that
cause dementia.

Question 3

Donepezil: Indications

Answer 3

Treats cognitive sx in AD, all stages

Question 4

Rivastigmine: Indications

Answer 4

Treats cognitive Sx
in mild/mod AD; PD
dementia

Question 5

Galantamine: Indications

Answer 5

Treats cognitive Sx

in mild/mod AD

Question 6

Cholinesterase-inhibitors: Side Effects

Answer 6

Primary effects: GI
(nausea, vomiting,
diarrhea, anorexia)
Secondary effects:
insomnia, vivid
dreams, bradycardia,
syncope

Question 7

Donepezil: Metabolism

Answer 7

CYP2D6 and 3A4 hepatic

metabolism

Question 8

Rivastigmine: Metabolism

Answer 8

Non-hepatic metabolism

Question 9

Galantamine: Metabolism

Answer 9

CYP2D6 and 3A4 hepatic

metabolism

Question 10

Gluatminergic antagonist?

Answer 10

Memantine

Question 11

Memantine: MOA

Answer 11

Low-moderate affinity,
voltage-dependent,
antagonist of NMDA
receptor activity. NMDA
receptors play an
important physiologic
role in long-term
potentiation (LTP) in the
hippocampus, which
underlies synaptic
plasticity involved in
learning. Excessive
stimulation of NMDA
receptors results in
excessive calcium influx
into cells, leading to a
pathophysiological
response (excitotoxicity).

Question 12

Memantine: Indications

Answer 12

FDA-approved for
treating mod-severe
AD (studies in mild
AD were
inconsistent).

Question 13

Memantine: Side Effects

Answer 13

Primary effects:
headaches,
constipation, agitation

Question 14

Memantine: Metabolism

Answer 14

Non-hepatic (P450);
decrease dose with
renal insufficiency

Question 15

Memantine: Drug Interactions

Answer 15

Decreases
metabolism of
buproprion and
trihexyphenidyl