Dementia Medications - Kinder Flashcards
Donepezil
AChE inhibitor
approved for dementia
galantamine
AChE inhibitor
approved for dementia
rivastigmine
AChE inhibitor
approved for dementia
tacrine
AChE inhibitor
approved for dementia
pralidoxome
cholinesterase reactivator
prevalence of AD
20% over 85yo
AD path
tau tangles, amyloid plaques
also - loss of cholinergic neurons
-marked decrase choline acetyltransferase
also possible excess of glutamate
direct acting cholinomimetic
bind to and activate mAChR and nAChR
indirect acting cholinomimetic
AChE inhibitor
cholinesterases
butylcholinesterase
acetylcholinesterase
target of AChE inhibitors - acetylcholinesterase
AChE
hydrolysis of ACh to choline and acetate
alcohol AChE inhibitors
alcohol group and quaternary ammonium
-positive charge
noncovalent and reversible, short lived
-binding to AChE
edrophonium
AChE inhibitor - alcohol
carbamic acid ester AChE inhibitors
carbamic acid ester of alcohol
-quaternary or tertiary ammonium group
positive charge or neurtal
neostigmine
carbamic acid ester AChE inhibitor
pyridostigmine
carbamic acid ester AChE inhibitor
physostigmine
carbamic acid ester AChE inhibitor
carbaryl
carbamic acid ester AChE inhibitor
binding of carbamic acid ester AChE inhibitor
to AChE - two step oricess
covalent bond of carbamoylated enzyme - more resistant to second step hydration
organophosphates
covalent and irreversible bind to AChE
charge neutral and highly lipid soluble
-CNS toxicity
echothiophate
organophosphate
parathion and malathion
organophosphate
insectisides
sarin and soman
organophosphate
nerve gas
charged AChE inhibitor
quaternary ammonium
no CNS effects
ex/ neostigmine, pyridostigmine, edrohonium, echothiophate, ambenonium
uncharged AChE inhibitor
tertiary ammonium
CNS distribution
physostigmine, donepezil, tacrine, rivastigmine, galantamine
organophosphates
lipid soluble - absorbed skin and conjunctiva
-dangerous to humans
CNS toxicity
covalent and irreversible binding to AChE
safe insecticide
malathion
organophosphate rapidly metabolized to inactive product in mammals
DOA for alcohols
reversible bind
weak - short lived
2-10 minutes
hydrogen bonding and electrostatic interactions
DOA for carbamate esters
2 step hydrolysis
2nd step - covalent bond
30min-6 hours
DOA for organophosphates
hundreds of hours
aging may occur - break O-P bond - even more stable
high AChE in CNS
convulsion, coma, resp arrest
AChE inhibitor on eye
miosis
accomodation
AChE inhibitor on heart
SA node - negative chronotropy
atria - negative inotropy
AV node - negative dromotropy (increased refractory)
ventricle - small decrease contractions
AChE inhibitor on blood vesels
artery - dilation
-high dose - constriction
vein - dilation
-high dose -constriction
AChE inhibitor on lung
bronchoconstriction
bronchosecretion
AChE inhibitor on GI
increase motility
sphincter relaxation
secretion stimulation
AChE inhibitor on urinary bladder
contract detrusor
relax trigone and sphincter
go pee
AChE inhibitor on glands
secretion
cardiac effect of AChE inhibitor and dose
moderate - mild HTN
toxic - hypotension
AChE inhibitor on NMJ
increase strength of contraction
fibrillation and fasciculation of muscle fiber - high concentrations
continued inhibition - depolarizing muscle blockade - to nondepolarizing blockade
tacrine
initial tx of dementia
-but hepatotoxic
combine AChE inhibitor with nondepolarizing neuromusc block agent
diminish neuromuscular blockade
exception - mivacurium
succinylcholine and AChE inhibitor
increase serum succinylcholine
prolong neuromuscular blockade
AChE inhibitor and cholinergic agonist
enhance cholinergic agonist
beta blocker and AChE inhibitor
enhance bradycardia
systemic corticosteroids and AChE inhibitor
enhance muscle weakness - pt with MG
AChE inhibitor intoxication
miosis salivation sweating bronchoconstriction vomiting diarrhea
route of admin for toxic AChE inhibitor
ingestion - GI sx first
percutaneous - sweating and muscle fasciculations
poison with lipid soluble agent - CNS involvement rapid - convulsion, coma, resp paralysis
death with AChE inhibitor
resp failure
diagnosis of AChE inhibitor poisoning
measure AChE activity in erythrocytes and plasma
antidote for cholinergic poisoning
atropine - mAChR antagonist
pralidoxome
cholinesterase re-activator
to regenerate AChE at NMJ
cholinesterase re-activator
pralidoxime
remove P group from active site of enzyme
must be given before aging
does not enter CNS - no effect of organophosphate poisoning
antidote for organophosphate
atropine
pralidoxime
benzo (anticonvulsant)
donepezil
tx mild to moderate and severe AD dementia
rapid absorption
one daily dosing
adverse of donepezil
GI urinary incontinence vivid dreams bradycardia syncope
galantamine
mild to moderate AD
rapid abosrption - t-1/2 7 hours
galantamine ADRs
GI, dizzy, weight loss, bradycardia and syncope
rivastigmine
tx mild to moderate AD
severe AD (transdermal patch)
and parkinsons dementia
rivastigmine ADRs
GI - less with transdermal
memantime
antagonist at NMDA glutamate receptor
normally - Mg ion block channel
- excess activation - prevent Mg reentering and blocking pore (with AD)
- memantine - blocks intrapore Mg site - effective receptor blocker
use of memantine
moderate-to severe AD
memantine adverse
dizzy
confusion, hallucinations
increased agitation and delusions