Pharm, Dementia, Kinder Flashcards
What are the ACHEI approved for dementia
donepezil
galantamine
rivastigmine
Tacrine
adverse effects of ACHEI
diffuse
CV, GI, eye, respiratory, urinary, CNS, NMJ
groups of cholinesterase inhibitors
alcohols
carbamic acid esters
organophosphates
structure of alcohol cholinesterase
quaternary amonium
+ charged
like edrophonium
noncovalent short lied
structure of crbamic acid ester cholinesterase inhibitor
quaternary or tertiaty ammonium groups (+ or neutral)
stigmines
binding of carbamic ester acids
2 steps
organophosphate structure of cholinesterase inhibitors
charged neutral
highly lipid soluble resulting in CNS toxicity
covalent irreversible binding
PK of qauternary charged ACHEI
reslativley insoluble in lipids
pareneteral preferred
no CNS
PK tertiary uncharged ACHEI
well absorbed all sires, CNS distribution, more toxic than quaternary carbamates
what drugs used for dementia are tertiary and uncharged ACHEI
donepezil, tacrine, rivastigmine, galantamine
why are organophosphates dangerous
readily abosrbed everywhere
distributed all parts of body
toxic organosphosphate, how do we recover
need to make more ACHE
oxime regenerator compound
“aging” process
after intial binding of organophosphates the enzyme will break a bond of inhibitor and further strenghten the phosphorus enzyme bond
continued inhibition of ACHE in NMJ
depolarizing NMJ blockade to nondepolarizing blockade (like succinylcholine)
uses of aCHEI
glaucoma, postoperative atony of bladder or GI
NMJ
alzheimers
dementia
tacrine withdrawn because
hepatotoxicity
DDI ACHE
nondepolarizing NMJ blockin agents (will diminish blockade) succinycholine (prolong blockade) cholinergic agonists (enhance) beta blockers (bradycardia) systemic corticosteorids (enhance mm weakness)
initial signs ACHE I intoxication
miosis salivation sweating bronchial constriction vomiting diarrhea
poisoning of lipid soluble ACHEI
confusion, ataxia, generalized convulsions, coma and respiratory paralysis
death by ACHEI
respiratory failure
Dx mild intoxication ACHE
ACHE activity in plasma and RBC
antidote for chilergic posisoning
atropine mACHR antagonist
atropine ineffective against
peripheral NMstimulation nACHR
pralidozime
cholinesterase reactivator to regenerate ACHE
does pralidoxie cross bbb
no
metabolism donepezil
CY2D6 and 3A4
donepezil used for what alzheimer dementia levels
mild to mod and severe
PD and lewy body too (off label)
adverse effects donepezil
GI especially on intiation
urinary incontinence, viivd dreams, bradycardia, syncope
half life donepezil
70 hours
daily dosing
galantamine used for
mild to mod alzheimer dementia
off label severe dementia or PD or lewy body
adverse effects galantamine
GI, dizziness, weight loss,
bradycardia and syncope
depression fatigue somnolence
metabolism rivastigmine
esterase hydrolysis
rivastigmine used for
mild to mod AD
severe AD in transdermal patch
Parkinsons dementia
and lewy body (off label)
side effects rivastigmine
high incidence nausea vomiting diarrhea in oral form
less with transdermal patch
brady cardia and syncope
MOA memantine
antagonist NMDA R glutamate
binds Mg site with longer time and so blocks only the excessive stimulation
use mematnine
mod to severe AD dementia
adverse effects memantine
well tolerated
fewer side effects
dizziness, confusion, hallucinations
increase agitation and delusional behaviors in some
