Dementia Pharm Flashcards
ACHase inhibitors- agents approved for use in pts w dementia
-donepezil
-galantamine
-rivastigmine
-tacrine
(DGRT)
Other cholinesterase inhibitors
- Ambenonium
- Echothiophate
- edrophonium
- neostigmine
- physostigmine
- pyridostigmine
Antimuscarinic compounds
-atropine
Cholinesterase reactivators
-pralidoxime
ACHase inhibitors- subgroups
- alcohols- edrophonium
- carbamic esters- neostigmine, pyridostigmine, physostigmine, carbaryl
- organophosphates (insecticides, n gases)
quaternary and charged ACHE inhibitors
- parenteral admin is preferred
- no CNS distribution
- neostigmine, pyridostigmine, echothiophate, ambeonium
tertiary and uncharged ACHE inhibitors
- well absorbed from all sites
- CNS distribution
- physostigmine, donepezil, galantamine, rivastigmine, tacrine (DGRT)
ACHE inhibitors- moa
- inhibition of ACHE
- ACH accum thruout the body- act of nACHRs and mACHRs
ACHE inhibitors- duration of action
- alcohols- short (2-10 min)
- carbamic acid esters- 30 min to 6 hrs
- organophosphates: aging (breaking 1 of oxygen-phosphorous bonds of inhibitor- strengthens the phosphorus-enzyme bond- stable)
ACHE inhibitors- organ system effects
- quaternary- no CNS effects
- organophosphates and tertiary- well abs after oral admin; CNS effects
- stim mACHRs
- stim nACHRs
ACHE inhibitors- CNS effects
- low conc- diffuse act of electroencephalogram
- high conc- generalized convulsions due to neuronal hyperstimulation
ACHE inhibitors- eye, resp, GI, urinary tracts
-these organs innervated by mACHRs (parasymp)
ACHE inhibitors- CV system
- inc activity of symp and parasymp ganglia (nACHRs and mACHRs) supplying the heart and mACHRs on cardiac cells
- parasymp tone dominates- CO dec
- net effects- modest bradycardia, dec in CO, inc in BP
ACHE inhibitors- NMJ
- inc strength of contraction
- fibrillation of m fibers and fasciculations- w high conc
- continued inhibition- progression of depolarizing neuromuscular blockade to nondepolarizing blockade
therapeutic uses of ACHE inhibitors-
- dementia
- eye (glaucoma, accommodative esotropia)
- GI and urinary tracts (postop atony, neurogenic bladder)
- NMJ (MG, curare-induced paralysis)
- heart (atrial arrhythmias)
- Alzheimer dz
ACHE inhibitors- dementia
dementia of Alzheimer type- def of intact cholinergic neurons
- Tacrine- high incidence of hepatotoxicity
- newer agents (less SEs)- donepezil, rivastigmine, galantamine
- also pts w dementia of Parkinson dz
drug-drug interactions
- nondepolarizing neuromuscular blocking agents: diminish NM blockade (Exception- mivacurium- blockade is prolonged)
- succinylcholine- enhance phase 1 block, antagonize phase 2 block
- cholinergic agonists
- B-blockers- enhance bradycardia
- systemic corticosteroids- enhance m weakness in MG
Acute intoxication
- signs- mACHR stimulation- miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
- ingestion- GI sx’s first
- percutaneous abs- sweating, m fasciculations in area
- death- resp failure
intoxication dx and tx
- dx- exposure hx and characteristic signs
- atropine (mACHR antagonist)- antidote for cholinergic poisoning!!!; decontamination (removal of clothing, washing of skin)
- regenerate ACHE at NMJ- cholinesterase regenerators (atropine is ineffective against peripheral NM stim- nACHRs)
Cholinesterase regenerators
(pralidoxime)
- regenerates active enzyme from organophosphorus-cholinesterase complex via removal of phosphorous group from active site of enzyme
- must be given before aging has occurred b/w organophosphate and cholinesterase!!!
- antidote for organophosphate exposure!!
Memantine- moa
[Glutamate (EAA of CNS)- contributes to Alzheimer’s dz by overstim glutamate Rs leading to excitotoxicity and neuronal cell death]
- antagonist of NDMA type of glutamate Rs!!
- under normal conditions, NMDA R ion channel is blocked by Mg ions
- excessive R act prevents Mg from reentering and blocking the channel pore- results in chronically open state and excessive Ca influx
- Memantine binds to intra-pore Mg state- R blocker only under conditions of excessive stim
Memantine- SEs
-dizziness- most common
