Dementia drugs Flashcards
Cholinesterase-inhibitors?
Donepezil, rivastigmine, galantamine
MOA of cholinesterase-inhibitors?
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.
Donepezil: Indications
Treats cognitive sx in AD, all stages
Rivastigmine: Indications
Treats cognitive Sx
in mild/mod AD; PD
dementia
Galantamine: Indications
Treats cognitive Sx
in mild/mod AD
Cholinesterase-inhibitors: Side Effects
Primary effects: GI (nausea, vomiting, diarrhea, anorexia) Secondary effects: insomnia, vivid dreams, bradycardia, syncope
Donepezil: Metabolism
CYP2D6 and 3A4 hepatic
metabolism
Rivastigmine: Metabolism
Non-hepatic metabolism
Galantamine: Metabolism
CYP2D6 and 3A4 hepatic
metabolism
Gluatminergic antagonist?
Memantine
Memantine: MOA
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).
Memantine: Indications
FDA-approved for treating mod-severe AD (studies in mild AD were inconsistent).
Memantine: Side Effects
Primary effects:
headaches,
constipation, agitation
Memantine: Metabolism
Non-hepatic (P450);
decrease dose with
renal insufficiency
Memantine: Drug Interactions
Decreases
metabolism of
buproprion and
trihexyphenidyl
